phenylephrine-hydrochloride and Intellectual-Disability

Exocrine pancreatic insufficiency in children can lead to lifelong complications related to malnutrition and poor growth. The clinical presentation can be subtle in the early stages of insufficiency as the large functional capacity of the pancreas is gradually lost. The pediatrician plays a crucial role in the early identification of these children to ensure a timely referral so that a diagnosis can be made and therapy initiated. Early nutritional therapy allows for prevention and correction of deficiencies, which leads to improved outcomes and survival. When insufficiency is suspected, the workup should start with an indirect test of exocrine pancreatic function, such as fecal elastase, to establish the diagnosis. Once a diagnosis is established, further testing to delineate the etiology should be pursued, with cystic fibrosis being high on the differential list and assessed for with a sweat test. Assessment of anthropometry at every visit is key, as is monitoring of laboratory parameters and physical examination findings that are suggestive of malabsorption and malnutrition. The mainstay of management is administration of exogenous pancreatic enzymes to facilitate digestion and absorption. [Pediatr Ann. 2019;48(11):e441-e447.].

Topics: Acyl-CoA Dehydrogenase, Long-Chain; Anus, Imperforate; Child; Child Nutrition Disorders; Chymotrypsin; Congenital Bone Marrow Failure Syndromes; Cystic Fibrosis; Dietary Fats; Ectodermal Dysplasia; Enzyme Replacement Therapy; Exocrine Pancreatic Insufficiency; Feces; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Intellectual Disability; Lipid Metabolism, Inborn Errors; Mitochondrial Diseases; Muscular Diseases; Nose; Nutrition Assessment; Pancreas; Pancreatic Diseases; Pancreatic Elastase; Pancreatic Function Tests; Pancreatitis, Chronic; Shwachman-Diamond Syndrome; Steatorrhea; Trypsinogen

Johanson-Blizzard syndrome (JBS) is considered as an infrequent, but clinically easily recognizable autosomal recessive entity by the pathognomonic combination of congenital exocrine pancreatic insufficiency and hypoplastic alae nasi, in addition to other distinctive findings such as scalp defects, hypothyroidism, and rectourogenital malformations. There are few reports of patients with JBS in association with facial clefting, referring all to types 2 to 6 of Tessier's classification that can be characterized properly as oblique facial clefts (OFCs). We describe the clinical aspects in four patients with JBS and extensive OFCs. In all of them, the diagnosis of JBS was confirmed by the demonstration of homozygous or compound-heterozygous mutations in the UBR1 gene. Additionally, we review three previously reported cases of JBS with OFCs. Taking into account a number of approximately 100 individuals affected by JBS that have been published in the literature we estimate that the frequency of OFCs in JBS is between 5% and 10%. This report emphasizes that extensive OFCs may be the severe end of the spectrum of facial malformations occurring in JBS. No obvious genotype phenotype correlation could be identified within this cohort. Thus, UBR1 should be included within the list of contributory genes of OFCs, although the exact mechanism remains unknown. © 2016 Wiley Periodicals, Inc.

Topics: Alleles; Anus, Imperforate; Cleft Palate; Consanguinity; Craniofacial Dysostosis; Diagnostic Imaging; DNA Mutational Analysis; Ectodermal Dysplasia; Eye Abnormalities; Female; Genetic Association Studies; Genotype; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Infant, Newborn; Intellectual Disability; Introns; Male; Maxillofacial Abnormalities; Mutation; Nose; Pancreatic Diseases; Phenotype; Ubiquitin-Protein Ligases

The N-end rule pathway is a unique branch of the ubiquitin-proteasome system in which the determination of a protein's half-life is dependent on its N-terminal residue. The N-terminal residue serves as the degradation signal of a protein and thus called N-degron. N-degron can be recognized and modifed by several steps of post-translational modifications, such as oxidation, deamination, arginylation or acetylation, it then polyubiquitinated by the N-recognin for degradation. The molecular basis of the N-end rule pathway has been elucidated and its physiological functions have been revealed in the past 30 years. This pathway is involved in several biological aspects, including transcription, differentiation, chromosomal segregation, genome stability, apoptosis, mitochondrial quality control, cardiovascular development, neurogenesis, carcinogenesis, and spermatogenesis. Disturbance of this pathway often causes the failure of these processes, resulting in some human diseases. This review summarized the physiological functions of the N-end rule pathway, introduced the related biological processes and diseases, with an emphasis on the inner link between this pathway and certain symptoms.

Topics: Aminoacyltransferases; Animals; Anus, Imperforate; Cardiovascular System; Ectodermal Dysplasia; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Intellectual Disability; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Mice; Neurodegenerative Diseases; Neurogenesis; Nose; Pancreatic Diseases; Protein Processing, Post-Translational; Signal Transduction; Spermatogenesis

Johanson-Blizzard syndrome (JBS) is a rare, autosomal recessive disorder characterized by exocrine pancreatic insufficiency, typical facial features, dental anomalies, hypothyroidism, sensorineural hearing loss, scalp defects, urogenital and anorectal anomalies, short stature, and cognitive impairment of variable degree. This syndrome is caused by a defect of the E3 ubiquitin ligase UBR1, which is part of the proteolytic N-end rule pathway. Herein, we review previously reported (n = 29) and a total of 31 novel UBR1 mutations in relation to the associated phenotype in patients from 50 unrelated families. Mutation types include nonsense, frameshift, splice site, missense, and small in-frame deletions consistent with the hypothesis that loss of UBR1 protein function is the molecular basis of JBS. There is an association of missense mutations and small in-frame deletions with milder physical abnormalities and a normal intellectual capacity, thus suggesting that at least some of these may represent hypomorphic UBR1 alleles. The review of clinical data of a large number of molecularly confirmed JBS cases allows us to define minimal clinical criteria for the diagnosis of JBS. For all previously reported and novel UBR1 mutations together with their clinical data, a mutation database has been established at LOVD.

Topics: Abnormalities, Multiple; Anus, Imperforate; Databases, Genetic; Dwarfism; Ectodermal Dysplasia; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Intellectual Disability; Mutation; Nose; Pancreatic Diseases; Phenotype; Ubiquitin-Protein Ligases

Johanson-Blizzard syndrome is a very rare autosomal recessive disorder caused by mutations in the Ubiquitin-Protein Ligase E3 Component N-Recognin 1 (UBR1) gene. The syndrome is characterized by exocrine pancreatic insufficiency and a wide range of additional clinical features, including aplasia or hypoplasia of the alae nasi, oligodontia, sensorineural hearing loss, hypothyroidism, scalp defects, mental retardation, and developmental delay. Several other abnormalities in different organs, particularly anorectal, urogenital, and cardiac anomalies have been reported since the first description of this syndrome four decades ago. UBR1 gene defects are underlying the disease. Only symptomatic treatment is available. Exocrine pancreas insufficiency plus abnormal alae nasi is pathognomonic for Johanson-Blizzard syndrome.

Topics: Abnormalities, Multiple; Anus, Imperforate; Child; Deafness; Ectodermal Dysplasia; Eponyms; Exocrine Pancreatic Insufficiency; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Intellectual Disability; Nose; Pancreatic Diseases; Ubiquitin-Protein Ligases

To study the clinical characteristics and diagnosis of the Johanson-Blizzard syndrome.. The clinical characteristics and diagnosing procedure of 1 case with Johanson-Blizzard syndrome were analyzed, and genetic analysis was made in diagnosing procedure, and 28 cases of Johanson-Blizzard syndrome with detailed clinical data were reviewed and analyzed.. A one year and nine months old girl, who was initially admitted to the hospital because of fatty diarrhea and increased frequency of defecation. Imperforate anus, and aplastic alae nasi was noticed after birth. On physical examination, short stature, mental retardation, tooth abnormalities and scalp defects were observed. Fat globule was found by routine stool test. Serum biochemistry showed an exocrine and endocrine pancreatic insufficiency, CT scan of the abdomen demonstrated fatty replacement of the pancreas, UBR1 gene analysis showed heterozygous for two missense changes. In all 29 cases, exocrine pancreatic insufficiency (72.4%) and hypoplasia of the alae nasi (93%) were the most common clinical manifestations, and sensorineural hearing loss (59%), scalp defects (69%) and hair thinning or upsweep of the hair (44.8%), hypothyroidism (44.8%), absence of permanent teeth (44.8%) and imperforate anus (21%) were also very common, but did not include consanguineous marriage of parents (10.3%).. Johanson-Blizzard syndrome is a rare autosomal recessive multisystem disorder, it is characterized by the association of congenital exocrine pancreatic insufficiency and hypoplasia or aplasia of the nasal wings, and can be diagnosed by clinical characteristics and UBR1 gene analysis.

Topics: Anus, Imperforate; Deafness; Ectodermal Dysplasia; Female; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Infant; Intellectual Disability; Nose; Pancreatic Diseases; Ubiquitin-Protein Ligases

Alopecia present from birth includes a broad differential diagnosis and often represents a diagnostic and therapeutic challenge for the involved physician.. An initial correct diagnosis and classification is essential because structural hair defects may be the expression of a genetic disorder affecting hair growth, part of a congenital syndrome with accompanying hair malformations, or a marker for an underlying metabolic disorder and may impact the mental and physical development of a child. Pathological hair loss rarely occurs in the first year of life; however, it may be a leading symptom of many congenital diseases.. In recent years, the clinical and microscopic features of hereditary hair shaft disorders have been characterized and classified. Furthermore, significant progress has been made in our knowledge of genes that control the normal development and differentiation of hair follicles, and thus the research is to define and classify the hair disorders within a genetic basis.. In this article we discuss several types of genotrichosis and provide a practical classification based on their clinical features.

Topics: Alopecia; Aneurysm; Carcinoma, Basal Cell; Child; Cleft Lip; Cleft Palate; Deafness; Ectodermal Dysplasia; Eczema; Facies; Fingers; Growth Disorders; Hair Diseases; Hallermann's Syndrome; Histiocytoma, Benign Fibrous; Humans; Hypotrichosis; Ichthyosis; Intellectual Disability; Keratitis; Langer-Giedion Syndrome; Microcephaly; Nose; Skin Diseases, Genetic; Skin Neoplasms

In 1966, Mietens and Weber reported four out of six siblings from a consanguineous couple with growth failure, dislocation of the head of the radii, bilateral flexion contracture of the elbows, short ulnae and radii, bilateral corneal opacities, horizontal and rotational nystagmus, strabismus, small, pointed nose and mild to moderate mental retardation. Since then, only three other cases have been reported. We report on two new cases, a pair of female twins aged 9 years. The patients were born after an uneventful, normal pregnancy, to young and non-consanguineous parents. After birth, physical findings included horizontal nystagmus and dislocation of both elbows because of abnormally short radii and ulnae in both twins. Further clinical examinations showed moderate psychomotor delay with marked language compromise. Karyotypes were normal in both girls. A review of the literature reveals that the Mietens-Weber syndrome is an uncommon disorder with a probable autosomal recessive pattern of inheritance. To our best knowledge, including the two cases reported here, only nine cases have been observed so far. The finding of congenital nystagmus and radii dislocation in a patient with mental retardation is probably nonrandom and is highly suggestive of Mietens-Weber syndrome.

Topics: Abnormalities, Multiple; Arm Bones; Cafe-au-Lait Spots; Child; Elbow; Female; Humans; Intellectual Disability; Joint Dislocations; Microcephaly; Nose; Nystagmus, Pathologic; Strabismus; Syndrome; Twins

Otolaryngologists frequently encounter nasal foreign bodies, particularly among children and mentally retarded patients. There are isolated reports describing the removal of unusual foreign bodies from the nose. But no comprehensive reviews of this important subject have been published for many years. This article includes a detailed discussion of the different types of nasal foreign bodies, the various clinical presentations, management options, and complications associated with nasal foreign bodies.

Topics: Adolescent; Adult; Aged; Ascariasis; Child; Child, Preschool; Foreign Bodies; Humans; Infant; Intellectual Disability; Middle Aged; Myiasis; Nose; Physical Examination

Topics: Abnormalities, Multiple; Diagnosis, Differential; Exocrine Pancreatic Insufficiency; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Intellectual Disability; Nose; Prognosis; Scalp; Tooth Abnormalities

Topics: Abnormalities, Multiple; Chromosome Deletion; Chromosomes, Human, Pair 2; Cleft Palate; Coloboma; Heart Septal Defects, Ventricular; Humans; Infant; Intellectual Disability; Male; Nose; Retina

Cerebro-Oculo-Nasal syndrome; a new multiple congenital anomaly/mental retardation syndrome was first reported by Richieri-Costa and Guion-Almeida in 1993 (Am J Med Genet 47:702-706) in two patients. To the best of our knowledge four additional cases have been reported. The main features of the syndrome are anophthalmia/microphthalmia, abnormal nares, and central nervous system anomalies. In this report, an additional sporadic case of this syndrome is presented. A 6-year-old girl from a non-consanguineous couple with normal prenatal growth parameters and retarded postnatal growth had anophthalmia, uplifted right nares with skin tag, and slight clefting at the tip of the nose, upper lip and gingiva. She also had a high-arched narrow palate, slightly low set ears, hypertelorism, a CNS defect and mental retardation. Additional findings were hypoplastic teeth with dental malocclusion, muscular hypotonia and midline hyperpigmentation over the anterior neck and the abdomen.

Topics: Abnormalities, Multiple; Anophthalmos; Brain; Child; Craniofacial Abnormalities; Female; Growth Disorders; Humans; Intellectual Disability; Nose; Syndrome; Tomography, X-Ray Computed

Twenty-one patients with frontonasal dysplasia were studied. A 2:1 male-to-female sex ratio and increased paternal and maternal ages at the time of conception were found. The significance is uncertain because of small sample size and lack of normal mean values for parental age in Brazil. Apparently, our series is the first to report macrocephaly (six cases). Our series also had a high frequency of patients with agenesis of the corpus callosum (12 cases), basal encephalocele (10 cases), lipoma of the corpus callosum (four cases), and mental deficiency (11 cases). Three patients had the combination of agenesis of the corpus callosum, mental deficiency, and micropenis. It is concluded that frontonasal dysplasia is pathogenetically heterogeneous, representing a regional defect which may not be a single developmental field or sequence. Causal genesis includes a dominantly inherited form, dup(2q), and autosomal recessive Shanske syndrome. Of unknown genesis are two subsets of frontonasal dysplasia patients: 1) the combination of agenesis of the corpus callosum, tibial hypoplasia, and hallucal duplication and 2) ophthalmofrontonasal dysplasia or oculoauriculofrontonasal dysplasia with associated ear tags and epibulbar dermoids.

Topics: Abnormalities, Multiple; Adolescent; Agenesis of Corpus Callosum; Child; Child, Preschool; Diagnosis, Differential; Facial Bones; Female; Genes, Dominant; Genes, Recessive; Humans; Hypertelorism; Infant; Intellectual Disability; Male; Nose; Parents; Sex Ratio; Skull; Terminology as Topic

Twenty-six persons with Laband syndrome have been reported in the literature to date. We report two further unrelated cases and suggest that a skeletal anterior open bite and symmetric soft tissue swelling of the vault of the palate be added to the variable features associated with the syndrome. There is clear evidence in the literature of autosomal dominant inheritance but our analysis indicates that in some cases recessive transmission is likely.

Topics: Abnormalities, Multiple; Child; Ear, External; Female; Fibromatosis, Gingival; Foot Deformities, Congenital; Genes, Dominant; Genes, Recessive; Hand Deformities, Congenital; Humans; Intellectual Disability; Male; Nails, Malformed; Nose; Palate; Syndrome; Tooth, Supernumerary

We report on a family where the propositus had G syndrome, including laryngeal cleft, and another relative had the facial anomalies typical of the BBB syndrome. We review the literature on the BBB and G syndrome, and argue that no clinical or laboratory criteria permit a differential diagnosis of the two syndromes. Therefore, we suggest that they should be considered variable expression of the same gene. The name BBBG syndrome is proposed for the amalgamated syndrome.

Topics: Abnormalities, Multiple; Adult; Diagnosis, Differential; Face; Female; Genes, Dominant; Humans; Hypertelorism; Hypospadias; Infant, Newborn; Intellectual Disability; Larynx; Male; Nose; Pedigree; Syndrome

Topics: Abnormalities, Multiple; Child; Ear; Face; Female; Foot Deformities, Congenital; Hand Deformities, Congenital; Humans; Infant; Intellectual Disability; Male; Mouth Abnormalities; Nose; Syndrome

Topics: Abnormalities, Drug-Induced; Bone and Bones; Coumarins; Ear; Eye Abnormalities; Female; Humans; Infant, Newborn; Intellectual Disability; Maternal-Fetal Exchange; Nose; Pregnancy; Risk; Warfarin

Topics: Body Height; Body Weight; Bronchial Diseases; Canada; Central Nervous System Diseases; Child, Preschool; Follow-Up Studies; Humans; Hypoxia; Infant; Infant, Newborn; Intellectual Disability; Intubation, Intratracheal; Lung Diseases; Nose; Positive-Pressure Respiration; Respiratory Distress Syndrome, Newborn; Respiratory Function Tests; Respiratory Tract Infections; Trachea; Vocal Cords

Topics: Child; Child, Preschool; Environment; Hearing Disorders; Humans; Intellectual Disability; Jaw Abnormalities; Lip; Malocclusion; Mother-Child Relations; Nose; Palate; Pharynx; Respiratory System; Schizophrenia, Childhood; Speech Disorders; Stuttering; Tongue; Voice

The efficacy of lysostaphin nasal spray and Neosporin ointment (Burroughs Wellcome & Co.) in altering nasal carriage of Staphylococcus aureus was studied with persistent carriers in an institution for mentally retarded children and adults. Treatment for 5 days with either agent significantly reduced carriage rates. This effect persisted through the 5th day after therapy with lysostaphin but not with Neosporin. By the 11th day after therapy, carriage rates in the treatment and control groups were not significantly different. Except for a single immediate wheal and flair skin test reaction, no other evidence of adverse reactions to topical lysostaphin was detected. No consistent changes in hemagglutination-inhibition titers to lysostaphin were observed after therapy. Lysostaphin appears to be slightly more effective than conventional topical antimicrobial therapy in reducing nasal carriage of staphylococci in this rigorously defined population of persistent carriers.

Topics: Adult; Aerosols; Anti-Bacterial Agents; Bacitracin; Bacteriophage Typing; Carrier State; Child; Clinical Trials as Topic; Diagnosis, Differential; Evaluation Studies as Topic; Hemagglutination Inhibition Tests; Humans; Intellectual Disability; Lysostaphin; Neomycin; Nose; Ointments; Placebos; Polymyxins; Skin Tests; Staphylococcal Infections; Staphylococcus; Time Factors

Topics: Adolescent; Carrier State; Child, Institutionalized; Disease Outbreaks; Drug Resistance, Microbial; Humans; Impetigo; Intellectual Disability; Male; Nose; Staphylococcal Infections; Staphylococcus; Tetracycline; Virulence

In this paper, we have carefully investigated the clinical phenotype and genotype of patients with Johanson-Blizzard syndrome (JBS) with diabetes mellitus as the main manifestation. Retinal vessel segmentation is an important tool for the detection of many eye diseases and plays an important role in the automated screening system for retinal diseases. A segmentation algorithm based on a multiscale attentional resolution network is proposed to address the problem of insufficient segmentation of small vessels and pathological missegmentation in existing methods. The network is based on the encoder-decoder architecture, and the attention residual block is introduced in the submodule to enhance the feature propagation ability and reduce the impact of uneven illumination and low contrast on the model. The jump connection is added between the encoder and decoder, and the traditional pooling layer is removed to retain sufficient vascular detail information. Two multiscale feature fusion methods, parallel multibranch structure, and spatial pyramid pooling are used to achieve feature extraction under different sensory fields. We collected the clinical data, laboratory tests, and imaging examinations of JBS patients, extracted the genomic DNA of relevant family members, and validated them by whole-exome sequencing and Sanger sequencing. The patient had diabetes mellitus as the main manifestation, with widened eye spacing, low flat nasal root, hypoplastic nasal wing, and low hairline deformities. Genetic testing confirmed the presence of a c.4463 T > C (p.Ile1488Thr) pure missense mutation in the UBR1 gene, which was a novel mutation locus, and pathogenicity analysis indicated that the locus was pathogenic. This patient carries a new UBR1 gene c.4463 T > C pure mutation, which improves the clinical understanding of the clinical phenotypic spectrum of JBS and broadens the genetic spectrum of the UBR1 gene. The experimental results showed that the method achieved 83.26% and 82.56% F1 values on CHASEDB1 and STARE standard sets, respectively, and 83.51% and 81.20% sensitivity, respectively, and its performance was better than the current mainstream methods.

Topics: Algorithms; Anus, Imperforate; Data Mining; Diabetes Mellitus; Diabetic Retinopathy; Ectodermal Dysplasia; Fundus Oculi; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Image Processing, Computer-Assisted; Intellectual Disability; Nose; Pancreatic Diseases; Perfusion

Topics: Anus, Imperforate; Child; Ectodermal Dysplasia; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Intellectual Disability; Nose; Pancreatic Diseases; Pathology, Molecular

The ubiquitin-proteasome system facilitates the degradation of unstable or damaged proteins. UBR1-7, which are members of hundreds of E3 ubiquitin ligases, recognize and regulate the half-life of specific proteins on the basis of their N-terminal sequences ("N-end rule"). In seven individuals with intellectual disability, epilepsy, ptosis, hypothyroidism, and genital anomalies, we uncovered bi-allelic variants in UBR7. Their phenotype differs significantly from that of Johanson-Blizzard syndrome (JBS), which is caused by bi-allelic variants in UBR1, notably by the presence of epilepsy and the absence of exocrine pancreatic insufficiency and hypoplasia of nasal alae. While the mechanistic etiology of JBS remains uncertain, mutation of both Ubr1 and Ubr2 in the mouse or of the C. elegans UBR5 ortholog results in Notch signaling defects. Consistent with a potential role in Notch signaling, C. elegans ubr-7 expression partially overlaps with that of ubr-5, including in neurons, as well as the distal tip cell that plays a crucial role in signaling to germline stem cells via the Notch signaling pathway. Analysis of ubr-5 and ubr-7 single mutants and double mutants revealed genetic interactions with the Notch receptor gene glp-1 that influenced development and embryo formation. Collectively, our findings further implicate the UBR protein family and the Notch signaling pathway in a neurodevelopmental syndrome with epilepsy, ptosis, and hypothyroidism that differs from JBS. Further studies exploring a potential role in histone regulation are warranted given clinical overlap with KAT6B disorders and the interaction of UBR7 and UBR5 with histones.

Topics: Animals; Anus, Imperforate; Caenorhabditis elegans; Cell Line; Ectodermal Dysplasia; Epilepsy; Growth Disorders; Hearing Loss, Sensorineural; HEK293 Cells; Histones; Humans; Hypothyroidism; Intellectual Disability; Mice; Mutation; Neurodevelopmental Disorders; Nose; Pancreatic Diseases; Proteasome Endopeptidase Complex; Receptors, Notch; Signal Transduction; Ubiquitin-Protein Ligases

Calpainopathies constitute a heterogeneous group of disorders resulting from deficiencies in calpains, calcium-specific proteases that modulate substrates by limited proteolysis. Clinical manifestations depend on tissue-specific expression of the defective calpain and substrate specificity. CAPN15, encoding the Drosophila small optic lobes (sol) homolog, was recently found to cause various eye defects in individuals carrying bi-allelic missense variants. Here we report on two siblings with manifestations reminiscent of Johanson-Blizzard syndrome including failure to thrive, microcephaly, global developmental delay, dysmorphic features, endocrine abnormalities and congenital malformations, in addition to eye abnormalities. Exome sequencing identified a homozygous 47 base-pair deletion in a minimal intron of CAPN15, including the splice donor site. Sequencing of cDNA revealed single exon skipping, resulting in an out-of-frame deletion with a predicted premature termination codon. These findings expand the phenotypic spectrum associated with CAPN15 variants, and suggest that complete loss-of-function is associated with a recognizable syndrome of congenital malformations and developmental delay, overlapping Johanson-Blizzard syndrome and the recently observed brain defects in Capn15 knockout (KO) mice. Moreover, the data highlight the unique opportunity for indel detection in minimal introns.

Topics: Abnormalities, Multiple; Alleles; Anus, Imperforate; Base Pairing; Calpain; Codon, Nonsense; Consanguinity; Developmental Disabilities; Ectodermal Dysplasia; Eye Abnormalities; Genetic Association Studies; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; INDEL Mutation; Intellectual Disability; Introns; Male; Microphthalmos; Muscle Hypotonia; Nose; Pancreatic Diseases; Pedigree; RNA Splice Sites; Sequence Deletion; Steatorrhea

Johanson-Blizzard Syndrome (JBS) is a rare autosomal recessive genetic disorder characterized by exocrine pancreatic insufficiency, distinct abnormal facial appearance and varying degrees of growth retardation. Variants in UBR1 gene are considered to be responsible for the syndrome. Here, we describe a 3-year old boy, who visited our clinic for severe growth retardation and frequent oily diarrhea. The physical examination revealed nasal alae aplasia, scalp defect, and maldescent of left testicle. Transabdominal ultrasound and computed tomography scan of his abdomen demonstrated complete fatty replacement of the pancreas. The clinical, laboratory, and imaging findings strongly suggest the diagnosis of hereditary pancreatitis. Whole exome sequencing revealed two rare compound heterozygous variants, c.2511T > G (p.H837Q) and c.1188T > G (p.Y396X), in the UBR1 gene of this boy, so, the diagnosis of JBS was established. This is the first report of Chinese patient with JBS, and our study indicates that transabdominal ultrasound and computed tomography are two useful and noninvasive imaging methods for the diagnosis and evaluation of JBS, and identification of these two novel variants expands the database of UBR1 gene variants. Furthermore, with the availability of the identification technology for these variants, prenatal diagnosis could be offered for future pregnancies.

Topics: Adipose Tissue; Anus, Imperforate; Child, Preschool; Ectodermal Dysplasia; Exome; Gene Frequency; Growth Disorders; Hearing Loss, Sensorineural; Heterozygote; Humans; Hypothyroidism; Intellectual Disability; Male; Models, Molecular; Nose; Pancreatic Diseases; Pancreatitis; Physical Examination; Tomography, X-Ray Computed; Ubiquitin-Protein Ligases; Ultrasonography

Somatic truncating variants of the WAC gene have been observed in patients with hematologic malignancies. Furthermore, de novo heterozygous constitutional pathogenic variants of WAC have recently been shown to cause a syndromic form of intellectual disability, DeSanto-Shinawi syndrome. It is unknown whether the constitutional pathogenic variants observed in the intellectual disability syndrome overlap with the somatic pathogenic variants observed in hematologic abnormalities. Herein, we report three patients with constitutional truncating variants of WAC in an attempt to address the above questions. All three of the patients had mild to moderate intellectual disability and dysmorphic features. We then reviewed the phenotypic features of 19 patients with DeSanto-Shinawi syndrome, including the three currently reported ones: eight and seven patients showed a bulbous nasal tip and short fingers, respectively. As for the pathogenetic mechanism, we demonstrated that the expression level of the mRNA derived from the wildtype allele was higher than that derived from the mutated allele, demonstrating nonsense-mediated mRNA decay. This observation makes a haploinsufficiency mechanism likely. Reviews of the constitutional and somatic pathogenic variants observed in patients with hematologic malignancies showed a significant overlap of the two. To date, no patients with DeSanto-Shinawi syndrome have been reported to have developed hematologic abnormalities, except for one of the three patients reported herein who developed leukopenia and thrombocytopenia at the age of 19 years. Larger data sets are required to determine hematologic prognosis of patients with constitutional WAC variants.

Topics: Adaptor Proteins, Signal Transducing; Adult; Child; Developmental Disabilities; Face; Female; Fingers; Frameshift Mutation; Haploinsufficiency; Human Growth Hormone; Humans; Intellectual Disability; Male; Nose; Phenotype; Pregnancy; Syndrome

Johanson-Blizzard Syndrome (JBS) was first described by Johanson and Blizzard. It exhibits autosomal recessive inheritance and is characterized by mutation in the UBR1 gene on the long arm of Chromosome 15. The phenotypic features as well as diarrhoea that occurs due to the exocrine pancreatic insufficiency constitute the main clinical symptoms. This article discusses Johanson-Blizzard Syndrome due to the case followed-up by us with the symptoms of deafness and diarrhoea as well as typical facial appearance.

Topics: Anus, Imperforate; Child, Preschool; Diarrhea; Ectodermal Dysplasia; Exocrine Pancreatic Insufficiency; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Infant; Intellectual Disability; Male; Nose; Pancreatic Diseases

We present a case of a child with pancreatic insufficiency and facial defects typical of Johanson-Blizzard syndrome (JBS), along with the more facultative anomalies of the JBS, such as those of the urogenital system including persistent urogenital sinus, urethral duplication and dysplastic kidneys. Fetal ultrasound in a 21-year-old G1P1 woman revealed ambiguous genitalia. Examination at birth revealed a phallic structure with urethral meatus, non-palpable gonads, two orifices in close proximity in the perineum, with the anterior being a common urogenital channel and the posterior, the rectum. A voiding cystourethrogram/genitogram showed bilateral high-grade vesicoureteral reflux and a common urogenital sinus extending 1.5 cm before dividing into three channels: the native urethra, an accessory urethra directed anteriorly towards the clitoris and a septate vagina with uterus didelphys. JBS was suspected by clinical presentation and confirmed by UBR1 molecular testing (46,XX). At 16 months of age, she underwent feminising genitoplasty and posterior sagittal anorectoplasty.

Topics: Anus, Imperforate; Diagnosis, Differential; Ectodermal Dysplasia; Female; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Infant, Newborn; Intellectual Disability; Nose; Pancreatic Diseases; Pregnancy; Ultrasonography, Prenatal; Urogenital Abnormalities; Young Adult

The N-end rule pathway controls the half-life of proteins based on their N-terminal residue. Positively charged type 1 N-degrons are recognized by a negatively charged pocket on the Zn finger named the UBR box. Here, we show that the UBR box is rigid, but bound water molecules in the pocket provide the structural plasticity required to bind different positively charged amino acids. Ultra-high-resolution crystal structures of arginine, histidine, and methylated arginine reveal that water molecules mediate the binding of N-degron peptides. Using a high-throughput binding assay and isothermal titration calorimetry, we demonstrate that the UBR box is able to bind methylated arginine and lysine peptides with high affinity and measure the preference for hydrophobic residues in the second position in the N-degron peptide. Finally, we show that the V122L mutation present in Johanson-Blizzard syndrome patients changes the specificity for the second position due to occlusion of the secondary pocket.

Topics: Anus, Imperforate; Binding Sites; Ectodermal Dysplasia; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Hypothyroidism; Intellectual Disability; Mutation, Missense; Nose; Pancreatic Diseases; Peptides; Protein Binding; Substrate Specificity; Ubiquitin-Protein Ligases; Water

Sensorineural hearing loss (SNHL) occurs in more than 80% of cases of Johanson Blizzard Syndrome (JBS). However, limited knowledge exists in medical literature of cochlear implantation (CI) outcomes in children with JBS. We report the case of a 5 year-old male with JBS and bilateral CI. While minimal progress in spoken language scores was noted after 4 years of bilateral CI use, substantial improvements in discrimination of speech sounds and audibility of spoken language and environmental sounds were documented. Cochlear implantation is an available treatment option of profound SNHL in children with JBS even if spoken language outcomes are marginal.

Topics: Anus, Imperforate; Child, Preschool; Cochlear Implantation; Cochlear Implants; Ectodermal Dysplasia; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Intellectual Disability; Male; Nose; Pancreatic Diseases; Speech Perception; Treatment Outcome

Johanson-Blizzard syndrome (JBS, MIM #243800) is a very rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, nasal wing hypoplasia, hypodontia, and other abnormalities. JBS is caused by mutations of the UBR1 gene (MIM *605981), encoding a ubiquitin ligase of the N-end rule pathway.. Molecular findings in a total of 65 unrelated patients with a clinical diagnosis of JBS who were previously screened for UBR1 mutations by Sanger sequencing were reviewed and cases lacking a disease-causing UBR1 mutation on either one or both alleles were included in this study. In order to discover mutations that are not detectable by Sanger sequencing, we designed a probe set for multiplex ligation-dependent probe amplification (MLPA) analysis of the UBR1 gene and analyzed the copy number status of all 47 UBR1 exons.. Our previous studies using Sanger sequencing could detect mutations in 93.1% of 130 disease-associated UBR1 alleles. Six patients with a highly suggestive clinical diagnosis of JBS and unsolved genotype were included in this study. MLPA analysis detected six alleles harboring exon deletions/duplications, thereby raising the mutation detection rate in the entire cohort to 97.7% (127/130 alleles).. We conclude that single or multi-exon deletions or duplications account for a substantial proportion of JBS-associated UBR1 mutations.

Topics: Adult; Alleles; Anus, Imperforate; Base Sequence; Child; Child, Preschool; DNA; DNA Mutational Analysis; Ectodermal Dysplasia; Exons; Female; Gene Deletion; Gene Duplication; Genotype; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Intellectual Disability; Male; Multiplex Polymerase Chain Reaction; Nose; Pancreatic Diseases; Phenotype; Ubiquitin-Protein Ligases

Bosma arhinia microphthalmia syndrome (Bosma syndrome)(OMIM 603457) is a congenital condition characterized by microphthalmia with coloboma, arhinia and endocrine findings in the setting of normal intelligence and brain structure. This condition is quite rare with fewer than 50 case reports and series. Although pathogenesis is presumed to be genetic, the cause remains unknown. We report an individual with Bosma syndrome who had bilateral colobomatous microphthalmia, arhinia, high arched palate, mild ear malformations, and hypogonadotropic hypogonadism requiring growth hormone treatment in childhood, and normal intelligence. Clinical evaluation was significant for a geometrically abnormal aorta with effacement of the sinotubular ridge, a finding not previously reported in this condition. An MRI revealed absent olfactory bulbs. Suggested criteria for diagnosis of Bosma should include arhinia, hypoplastic maxilla, normal cognition, and hypogonadotropic hypogonadism in males.

Topics: Abnormalities, Multiple; Adult; Brain Diseases, Metabolic, Inborn; Choanal Atresia; Coloboma; Corneal Opacity; Facial Bones; Humans; Intellectual Disability; Magnetic Resonance Imaging; Male; Microcephaly; Microphthalmos; Nose; Olfactory Bulb

The Simpson-Golabi-Behmel syndrome (SGBS) is an overgrowth condition characterised by macrosomia, mental deficiency, large head, prominent skull sutures, midface deficiency, hypertelorism, broad nose, wide mouth, macroglossia, malocclusion, highly arched palate, and musculoskeletal and limb abnormalities. The aim of this case report is to present clinical and oral findings of an 8-year-old boy who had been diagnosed with SGBS.. This patient had supernumerary nipples on the right side, cubitus valgus webbed fingers, scoliosis, umbilical hernia, a coarse face, macrocephaly, hypertelorism, a short broad nose, a wide mouth, a straight facial profile and hearing loss. The patient also had macroglossia, diastemas, over-retained primary tooth, absent mandibular permanent central incisors, and highly arched palate. Lateral cephalometric analysis revealed a large anterior cranial base, a large maxilla and mandible, a large inferior face height, and skeletal Class III jaw relationship.. After extraction of the over-retained primary central tooth, a partial prosthesis was fabricated in order to maintain function. The patient has been recalled regularly at 6-month intervals for 2 years. Over the following years the prosthesis was replaced due to facial growth.. Long term follow-up is essential for the patient with SGBS. Preventive dental care, including oral hygiene instructions, diet counselling and the use of fluoride has been implemented.

Topics: Anodontia; Arrhythmias, Cardiac; Cephalometry; Child; Denture, Partial, Removable; Diastema; Follow-Up Studies; Genetic Diseases, X-Linked; Gigantism; Heart Defects, Congenital; Humans; Hypertelorism; Incisor; Intellectual Disability; Macroglossia; Macrostomia; Male; Malocclusion, Angle Class III; Nose; Palate; Tooth, Deciduous

Johanson-Blizzard Syndrome (JBS) (MIM #243800) is a rare autosomal recessive genetic disorder characterized by exocrine pancreatic insufficiency, abnormal facial appearance and varying degrees of mental retardation. Mutations in UBR1 gene (MIM *605981) are considered to be responsible for the syndrome. Here, we report a 3 year-old mentally normal JBS girl. The patient presented with exocrine pancreatic insufficiency as well as failure-to-thrive. On dysmorphological examination, she was noted to have an abnormal hair pattern with frontal upsweep and alae nasi hypoplasia. With these findings, JBS diagnosis was established clinically. Molecular analysis of the UBR1 gene revealed two inherited novel mutations; one coming from each parent. These novel mutations were c. 1280T>G and c. 2432+5G>C, and they were found to be disease causing via in-silico analysis. In conclusion, for patients with longstanding exocrine pancreatic insufficiency, it should be considered as being symptomatic of a far broader picture. To omit connection with rare genetic diseases, such as Johanson-Blizzard Syndrome, a detailed dysmorphological examination ought to be performed.

Topics: Anus, Imperforate; Child, Preschool; DNA Mutational Analysis; Ectodermal Dysplasia; Female; Genetic Association Studies; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Intellectual Disability; Mutation, Missense; Nose; Pancreatic Diseases; Phenotype; Point Mutation; Ubiquitin-Protein Ligases

Topics: Anus, Imperforate; Ectodermal Dysplasia; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Intellectual Disability; Mutation; Nose; Pancreatic Diseases; Ubiquitin-Protein Ligases

Johanson-Blizzard syndrome (JBS); (OMIM: 243800) presents with features of malabsorption and dysmorphic features with onset of symptoms in infantile age group. The disorder was first described in the year 1971 with report of the first Indian case in 2004. We discuss two rare phenotypes (hepatitis and anemia) in a molecularly confirmed case of JBS.

Topics: Anemia; Anus, Imperforate; Chromosomes, Human, Pair 15; Ectodermal Dysplasia; Genes, Recessive; Genetic Testing; Genotype; Growth Disorders; Hearing Loss, Sensorineural; Hematologic Tests; Hepatitis; Humans; Hypothyroidism; Infant; Intellectual Disability; Male; Mutation; Nose; Pancreatic Diseases; Phenotype; Ubiquitin-Protein Ligases

Johanson-Blizzard syndrome is a rare congenital autosomal recessive disease characterized by the association of congenital deficiency of the exocrine pancreatic function and multiple malformations. One of the most common manifestations of this pathology is sensorineural hearing loss of different severity and anomalous development of the inner ear. The case of cochlear implantation in the patient presenting with bilateral sensorineural deafness, congenital malformation of the inner ear, and stenosis of the internal auditory canal is reported.

Topics: Anus, Imperforate; Child, Preschool; Cochlear Implantation; Ectodermal Dysplasia; Growth Disorders; Hearing Loss, Sensorineural; Hearing Tests; Humans; Hypothyroidism; Intellectual Disability; Male; Nose; Pancreatic Diseases; Treatment Outcome

Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive disorder resulting from loss-of-function mutations in the UBR1 gene. JBS can be easily recognized by its unique clinical presentation (including exocrine pancreatic insufficiency, hypoplasia/aplasia of the alae nasi, congenital scalp defects, sensorineural hearing loss, growth retardation, psychomotor retardation, and anal and genitourinary anomalies). The objective of this study is to report on the first familial case of gender-discordant twins presenting JBS and a novel mutation in the UBR1 gene. We also review literature describing molecularly confirmed cases of JBS. The female twin developed refractory severe diarrhea after the second month of life and died at the age of 3 months. The male twin also developed diarrhea and failure to thrive after the 3 month of life but improved when nutrition support and pancreatic enzyme replacement was started, and he has survived into adolescence. Both patients presented typical clinical features of JBS. A homozygous nonsense mutation (c.3682C>T; p.Q1228X) in UBR1 was confirmed. Severe presentation of JBS usually involves deleterious (nonsense, frameshift, or splice-site) mutations in the UBR1 gene that are thought to completely abolish the expression of a functional protein product, as in this familial case; however, milder presentation of JBS has occasionally been observed with missense mutations in at least 1 of the 2 copies of UBR1, in which there may be residual activity of the product of this gene. Early diagnosis and adequate treatment are crucial for a favorable outcome.

Topics: Adolescent; Anus, Imperforate; Codon, Nonsense; Ectodermal Dysplasia; Female; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Intellectual Disability; Male; Nose; Pancreatic Diseases; Pedigree; Sequence Analysis, DNA; Ubiquitin-Protein Ligases

Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive syndrome characterized by dysmorphic nasal alae, ectodermal abnormalities, exocrine pancreatic insufficiency and early growth failure. Most patients are diagnosed by clinical criteria prenatally or in early infancy. Nonsense, frame shift and splice-site mutations of the ubiquitin ligase gene (UBR1) lead to early loss of acinar cells in individuals with JBS.. We describe a previously asymptomatic patient with ectodermal dysplasia presenting with sudden onset exocrine pancreatic insufficiency in adolescence. The family reports an identical twin brother with similar symptoms.. This case illustrates that the phenotypic variability of pancreatic involvement in JBS may be subtle and may not manifest until the second decade of life. We suspect that this mild phenotype results from mutations in UBR1 allowing for partial function.

Topics: Abnormalities, Multiple; Adolescent; Anus, Imperforate; Diagnosis, Differential; Ectodermal Dysplasia; Exocrine Pancreatic Insufficiency; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Intellectual Disability; Male; Nose; Pancreatic Diseases; Phenotype; Syndrome

The patient reported here displayed most characteristic features of Binder syndrome (OMIM: 155050), a rare maxillonasal malformation with unknown etiology. She was sent for genetic evaluation at the age of 10 years because of facial dysmorphism and borderline intellectual disability. Cytogenetic analyses showed a de novo supernumerary small ring chromosome with a pericentromeric region of chromosome 5 in all lymphocytes. Array painting revealed that the marker contains a 20,950-kb genomic region comprising cytogenetic band 5p14.1q11.1. Additionally, 7 reports have been published in the literature with partial trisomy of chromosome 5 overlapping with our case. These 8 cases were analyzed for phenotype/genotype correlation which suggested that the maxillonasal anomalies of Binder phenotype and trisomy of the pericentromeric region of chromosome 5 may be in causal relationship. Future functional annotation studies of genes localized in this genomic region should take this into consideration. To the best of our knowledge, this is the first report on a patient with association of a chromosome abnormality and clinical characteristics of Binder phenotype.

Topics: Child; Chromosome Aberrations; Chromosomes, Human, Pair 5; Cytogenetic Analysis; Female; Humans; In Situ Hybridization, Fluorescence; Intellectual Disability; Maxilla; Maxillofacial Abnormalities; Nose; Phenotype; Trisomy

Here we apply objective, reliable methods of dysmorphology diagnosis to a patient with Johanson-Blizzard syndrome (MIM #243800). Using an extensive normative database, we computed standardized scores on a graded continuum for operational definitions of nasal alar hypoplasia, a commonly observed feature of this condition.. Most of these measurements in this case were greater than 2 standard deviations below the mean, adjusted for age, gender, and ethnicity.. This report provides a worked example of quantitative anthropometric assessment in the context of a case report, using tools that may find general application in clinical genetics.

Topics: Abnormalities, Multiple; Anus, Imperforate; Cephalometry; Ectodermal Dysplasia; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Infant; Intellectual Disability; Male; Nose; Pancreatic Diseases; Ubiquitin-Protein Ligases

We present clinical features and genetic diagnosis in an Indian infant diagnosed with Johanson- Blizzard syndrome. This is a rare, autosomal recessive genetic condition with multi-system involvement and a characteristic facies. Molecular genetic testing is important to confirm the clinical diagnosis and offer prenatal diagnosis in future pregnancies.

Topics: Anus, Imperforate; Ectodermal Dysplasia; Female; Genetic Testing; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; India; Infant, Newborn; Intellectual Disability; Nose; Pancreatic Diseases

Topics: Adult; Anus, Imperforate; Ectodermal Dysplasia; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Intellectual Disability; Male; Nose; Pancreatic Diseases; Pancytopenia; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

Oral rehabilitation of a child with Johanson-Blizzard syndrome (JBS).. JBS is an extremely rare inherited disorder characterized by unusually small nose that appears 'beak shaped' due to the absence (aplasia) or underdevelopment (hypoplasia) of the nostrils (nasal alae), abnormally small, malformed primary (deciduous) teeth and misshapen or absent secondary (permanent) teeth, hearing disorder, hypothyroidism, dwarfism, malabsorption and mental retardation. It is sometimes described as a form of ectodermal dysplasia.. Oral findings in JBS are very obscure in the literature. The present report describes oral findings in an 8 years old boy with JBS and his oral rehabilitation.. JBS has an emotional consequence for the affected individuals at early ages. Oral rehabilitation in this case had a very positive impact on the child's mind.. Early identification and treatment of this disease is of great importance to rehabilitate the patient on functional, esthetic and psychological front.

Topics: Anodontia; Anus, Imperforate; Cheilitis; Child; Crowns; Dental Caries; Denture, Partial, Fixed; Ectodermal Dysplasia; Facies; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Incisor; Intellectual Disability; Male; Nose; Pancreatic Diseases; Pulpotomy; Space Maintenance, Orthodontic; Tongue

Topics: Adult; Amino Acid Sequence; Base Sequence; Child; Child, Preschool; Codon; DNA-Binding Proteins; Facies; Female; Fingers; Gene Order; Hair Diseases; Hand Deformities, Congenital; Humans; Intellectual Disability; Langer-Giedion Syndrome; Male; Molecular Sequence Data; Mutation; Nose; Radiography; Repressor Proteins; Transcription Factors

Johanson-Blizzard syndrome is a rare autosomal recessive disorder, characterized by exocrine pancreatic deficiency and a wide range of other abnormalities. We present here an infant with failure to thrive, exocrine pancreatic deficiency, short stature and developmental delay, cutis aplasia on the scalp, aplasia of alae nasi, hypospadias, hypothyroidism, myxomatous mitral valve, and patent ductus arteriosus. Molecular studies revealed a novel homozygous nonsense mutation in exon 38 of the UBR1 gene, which confirmed the diagnosis of Johanson-Blizzard syndrome. It should be acknowledged that the combination of exocrine pancreatic insufficiency and nasal wing hypo-aplasia is pathognomonic for this syndrome. Prompt diagnosis and exact monitoring of the patients with JBS are required to avoid further complications.

Topics: Anus, Imperforate; Codon, Nonsense; Deafness; Ectodermal Dysplasia; Exocrine Pancreatic Insufficiency; Exons; Growth Disorders; Hearing Loss, Sensorineural; Homozygote; Humans; Hypothyroidism; Infant; Intellectual Disability; Male; Nose; Pancreatic Diseases; Ubiquitin-Protein Ligases

Johanson-Blizzard syndrome (JBS; OMIM 243800) is an autosomal recessive disorder that includes congenital exocrine pancreatic insufficiency, facial dysmorphism with the characteristic nasal wing hypoplasia, multiple malformations, and frequent mental retardation. Our previous work has shown that JBS is caused by mutations in human UBR1, which encodes one of the E3 ubiquitin ligases of the N-end rule pathway. The N-end rule relates the regulation of the in vivo half-life of a protein to the identity of its N-terminal residue. One class of degradation signals (degrons) recognized by UBR1 are destabilizing N-terminal residues of protein substrates.. Most JBS-causing alterations of UBR1 are nonsense, frameshift or splice-site mutations that abolish UBR1 activity. We report here missense mutations of human UBR1 in patients with milder variants of JBS. These single-residue changes, including a previously reported missense mutation, involve positions in the RING-H2 and UBR domains of UBR1 that are conserved among eukaryotes. Taking advantage of this conservation, we constructed alleles of the yeast Saccharomyces cerevisiae UBR1 that were counterparts of missense JBS-UBR1 alleles. Among these yeast Ubr1 mutants, one of them (H160R) was inactive in yeast-based activity assays, the other one (Q1224E) had a detectable but weak activity, and the third one (V146L) exhibited a decreased but significant activity, in agreement with manifestations of JBS in the corresponding JBS patients.. These results, made possible by modeling defects of a human ubiquitin ligase in its yeast counterpart, verified and confirmed the relevance of specific missense UBR1 alleles to JBS, and suggested that a residual activity of a missense allele is causally associated with milder variants of JBS.

Topics: Adolescent; Anus, Imperforate; Child; Deafness; Ectodermal Dysplasia; Female; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Intellectual Disability; Mutation; Mutation, Missense; Nasal Mucosa; Nose; Pancreatic Diseases; Signal Transduction; Ubiquitin-Protein Ligases

Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive disease characterized by exocrine pancreatic insufficiency, hypoplastic or aplastic nasal alae, cutis aplasia on the scalp, and other features including developmental delay, failure to thrive, hearing loss, mental retardation, hypothyroidism, dental abnormalities, and anomalies in cardiac and genitourinary systems. More than 60 cases of this syndrome have been reported to date. We describe the case of a male infant with typical symptoms of JBS. In addition, a new clinical feature which has not previously been documented, that is anemia requiring frequent blood transfusions and mild to moderate thrombocytopenia was observed. A molecular study was performed which revealed a novel homozygous UBR1 mutation. Possible explanations for this new association are discussed.

Topics: Animals; Anus, Imperforate; Base Sequence; Deafness; DNA Mutational Analysis; Ectodermal Dysplasia; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Infant; Intellectual Disability; Male; Molecular Sequence Data; Nose; Pancreatic Diseases; Sequence Alignment

Topics: Abnormalities, Multiple; Child, Preschool; Developmental Disabilities; Facies; Female; Fetal Growth Retardation; Foot Deformities, Congenital; Growth Disorders; Humans; Intellectual Disability; Nose

Topics: Abnormalities, Multiple; Female; Humans; Infant, Newborn; Intellectual Disability; Microcephaly; Nose; Nucleic Acid Hybridization; Syndactyly

In this paper, I describe the investigations in three members of an extended consanguineous family from Saudi Arabia, in which nine members show severe mental retardation, long eyelashes, high nasal bridge, underdeveloped malae, low hanging columella, thin upper vermillion, and everted lower vermillion, retrognathia, and an open mouth apparently caused by mandibular dentoalveolar protrusion. Pedigree analysis makes it likely that this is an autosomal recessively inherited disorder. A detailed literature search failed to show a similar entity.

Topics: Abnormalities, Multiple; Child; Consanguinity; Female; Genes, Recessive; Humans; Intellectual Disability; Male; Mouth; Nose; Pedigree; Saudi Arabia; Young Adult

Topics: Abnormalities, Multiple; Anophthalmos; Brain; Craniosynostoses; Humans; Infant; Intellectual Disability; Male; Nose; Phenotype; Severity of Illness Index; Skull; Syndrome; Ultrasonography

Here we report on 10 male patients with frontonasal dysplasia, cleft lip/palate, mental retardation, lack of language acquisition, and severe central nervous system involvement. Imaging studies disclosed absence of the corpus callosum, midline cysts, and an abnormally modeled cerebellum. Neuronal heterotopias were present in five patients and parieto-occipital encephalocele in three patients. We suggest that this pattern found exclusively in males, most likely represents a newly recognized syndrome distilled from the group of disorders subsumed under frontonasal dysplasia.

Topics: Adult; Brazil; Central Nervous System; Child; Child, Preschool; Developmental Disabilities; Frontal Bone; Humans; Infant; Intellectual Disability; Language Development Disorders; Male; Nose; Syndrome

Acrodysostosis is a rare syndrome characterized by peripheral dysostosis, nasal hypoplasia and frequently mental retardation. Only one adult case of acrodysostosis has been reported to have neurologic symptoms. We report one further adult case of acrodysostosis with severe neurologic findings including myelopathy and spastic paraparesis due to diffuse spinal stenosis and recurrent deep vein thrombosis possibly caused by neurologic deficits.. We report a 43-year-old woman who had back and neck pain with weakness in the extremities of several years. 1~year before admission to our hospital, she had been treated with a missed diagnosis of sero (-) spondyloarthropathy but had not benefited. She became unable to walk, thereafter she underwent decompression surgery with a diagnosis of degenerative spinal stenosis. She presented at our outpatient department complaining of lowback pain and difficulty walking. She had marked facial and peripheral appearance of acrodysostosis. Spinal MRI revealed extensive spinal stenosis. A diagnosis was made through the genetic investigation, clinical and radiological findings. Spastic paraparesis were detected. There was widespread neuropathic pain. 15 days after admission, she developed swelling and redness of the left lower extremity and the venous doppler ultrasonography showed left acute and right past DVT. We treated DVT with anticoagulant therapy. Gabapentin and Baclofen were initiated for neuropathic pain and spasticity. A conventional rehabilitation program was performed. She left walking with a walker without pain and spasticity.. We would like to remind physicians to be aware of peripheral malformations as signs of skeletal dysplasias and to consider acrodysostosis in the differential diagnosis. Although it is a rare condition, if diagnosed early, possible complications can be treated and outcomes may be improved.

Topics: Adult; Anticoagulants; Dysostoses; Female; Hand Deformities, Congenital; Humans; Intellectual Disability; Nose; Paraparesis, Spastic; Spinal Stenosis; Syndrome; Venous Thrombosis

Floating-Harbor syndrome is a rare disorder which is clinically characterized by short stature, retarded speech development, delayed bone ages, triangular face, bulbous nose and thin lips. We described two cases with Floating-Harbor syndrome and briefly reviewed the relevant literature.

Topics: Abnormalities, Multiple; Child, Preschool; Craniofacial Abnormalities; Diagnosis, Differential; Dwarfism; Face; Facial Bones; Female; Fingers; Hearing Loss; Heart Septal Defects, Ventricular; Humans; Infant; Intellectual Disability; Male; Mouth Abnormalities; Nose; Pulmonary Valve Stenosis; Speech Disorders; Syndrome

Here, we report on a newly recognized syndrome in a Brazilian family with three affected women, who had a Marfanoid habitus; long face; hypotelorism; long, thin nose; long, thin hands and feet; and language and learning disabilities. The disorder is compatible with autosomal dominant inheritance.

Topics: Abnormalities, Multiple; Adolescent; Adult; Craniofacial Abnormalities; Facies; Family Health; Female; Foot; Genes, Dominant; Hand; Humans; Intellectual Disability; Language; Learning Disabilities; Marfan Syndrome; Nose; Syndrome

Topics: Child; Humans; Intellectual Disability; Intermittent Positive-Pressure Ventilation; Male; Muscular Dystrophies; Nose; Severity of Illness Index

Johanson-Blizzard syndrome (OMIM 243800) is an autosomal recessive disorder that includes congenital exocrine pancreatic insufficiency, multiple malformations such as nasal wing aplasia, and frequent mental retardation. We mapped the disease-associated locus to chromosome 15q14-21.1 and identified mutations, mostly truncating ones, in the gene UBR1 in 12 unrelated families with Johanson-Blizzard syndrome. UBR1 encodes one of at least four functionally overlapping E3 ubiquitin ligases of the N-end rule pathway, a conserved proteolytic system whose substrates include proteins with destabilizing N-terminal residues. Pancreas of individuals with Johanson-Blizzard syndrome did not express UBR1 and had intrauterine-onset destructive pancreatitis. In addition, we found that Ubr1(-/-) mice, whose previously reported phenotypes include reduced weight and behavioral abnormalities, had an exocrine pancreatic insufficiency, with impaired stimulus-secretion coupling and increased susceptibility to pancreatic injury. Our findings indicate that deficiency of UBR1 perturbs the pancreas' acinar cells and other organs, presumably owing to metabolic stabilization of specific substrates of the N-end rule pathway.

Topics: Abnormalities, Multiple; Amino Acid Sequence; Animals; Chromosome Mapping; Chromosomes, Human, Pair 15; Humans; Intellectual Disability; Maxillofacial Abnormalities; Mice; Molecular Sequence Data; Mutation; Nose; Pancreas; Pancreatic Diseases; Syndrome; Ubiquitin-Protein Ligases

A subtle balanced translocation involving the terminal regions of 1q and 3p was identified in a large family by high-resolution karyotype analysis and confirmed by fluorescence in situ hybridization (FISH) analysis. In this family, segregation of a balanced t(1:3)(q42.3;p25) chromosome translocation led to two types of viable unbalanced complements. The proband inherited the derivative chromosome 3, resulting in partial trisomy of 1q and partial monosomy of 3p. A paternal uncle and cousin had the reciprocal rearrangement with a derivative of chromosome 1, resulting in partial monosomy for 1q and partial trisomy for 3p. While profound mental and physical retardation and congenital heart defects were characteristics for both rearrangements, facial dysmorphism was quite distinct for each imbalance. Individuals who had the derivative chromosome 3 had a long face, wide eyebrows, small palpebral fissures, hypertelorism, prominent glabella, a large tip of the nose, long philtrum with thin upper lip, and low set-ears. In contrast, family members with the derivative of chromosome 1 had a tall forehead with bifrontal narrowing, full and large cheeks, and large simple ears. Since the translocated segments are small and approximately equal in size in this family, it is not surprising that viability was seen in individuals with both types of adjacent-1 segregation. In this kindred, the ratio of normal to abnormal individuals born to balanced carriers is believed to be about 1:1.5. This suggests that the recurrence risk for carriers is 50%.

Topics: Abnormalities, Multiple; Adult; Chromosome Banding; Chromosome Segregation; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 3; Face; Family Health; Fatal Outcome; Female; Growth Disorders; Heart Defects, Congenital; Humans; Hypertelorism; In Situ Hybridization, Fluorescence; Infant; Infant, Newborn; Intellectual Disability; Karyotyping; Male; Nose; Pedigree; Translocation, Genetic

An interesting case of a seven years old boy with a combination of clinical, genetic, radiological, pathologic and dental findings is presented in view of Seckel syndrome literature. General appearance of the patient was characterized by small forehead, posteriorly slanted ears, slightly beaked nose, midfacial hypoplasia very stunted stature with microcephaly. He had borderline mental retardation with normal motor development. Class II dentoskeletal pattern with mild overjet and open bite, congenitally missing permanent teeth, microdontia, enamel hypoplasia, taurodontism and dentinal dysplasia was observed according to the clinical and radiographic examination. In conclusion, Seckel syndrome is not encountered routinely in dental clinics, this case illustrates the importance of dental care in such a rare condition.

Topics: Anodontia; Child; Craniofacial Abnormalities; Dental Enamel Hypoplasia; Dental Pulp Cavity; Dentin Dysplasia; Dwarfism; Ear, External; Forehead; Humans; Intellectual Disability; Male; Malocclusion, Angle Class II; Microcephaly; Nose; Open Bite; Syndrome; Tooth Abnormalities

Two sisters are reported with up-slanting palpebral fissures, hypertelorism, ptosis, a broad, bifid nasal tip, a high-arched palate, mental retardation, abnormal EEG and hand malformations in one of the patients. The girls' parents originate from the same village. Although the findings resemble the recently defined neurofaciodigitorenal syndrome, some findings suggest that this is a newly recognized syndrome.

Topics: Abnormalities, Multiple; Blepharoptosis; Child; Child, Preschool; Electroencephalography; Family Health; Female; Humans; Hypertelorism; Intellectual Disability; Nose; Nuclear Family; Tooth Abnormalities

We report a Brazilian boy, born to normal and nonconsanguineous parents showing, among other signs, brachycephaly, a wide forehead, a widow's peak, hypertelorism, wide palpebral fissures with multiple eyelid colobomas, a broad nasal root, a long philtrum, macrostomia, prominent lips, a high arched palate, a midline alveolar cleft, a small and grooved chin, ear anomalies, structural anomaly of the corpus callosum, and mental retardation. To our knowledge this additional patient defines a particular clinical condition previously reported [Guion-Almeida M.L. Richieri-Costa A. (1999) Clinical Dysmorphol 8;1-4; Masuno M. et al. (2000) Clin Dysmorphol 9:59-60].

Topics: Abnormalities, Multiple; Agenesis of Corpus Callosum; Child; Coloboma; Diagnosis, Differential; Ear; Eyelids; Family Health; Humans; Intellectual Disability; Macrostomia; Male; Nose; Phenotype

To describe the craniofacial morphology, dentition, and hand maturity in four siblings with Seckel syndrome.. Two boys and two girls, with Seckel syndrome. The children studied showed extreme growth retardation, severe microcephaly, bird-headed profile with receding chin, prominent nose, mental retardation, and extremely delayed skeletal maturation. The growth hormone axis and pituitary thyroid function was normal.. Skeletal and dental development were investigated from radiographic material, and a cephalometric analysis was performed from profile radiographs.. The craniums were remarkably small with an extremely short anterior cranial base (-4.3 to -5.5 standard units) and maxillary length (-3.8 to -4.7 SU). Differences in the morphology of the sella turcica were observed in girls and boys. Tooth maturity progressed normally. Tooth agenesis and tooth malformations were observed. Taurodontic root morphology was observed only in the girls. The approximate skeletal maturity showed retardation from 4 years 3 months to 4 years 11 months. Malformations of the hand-wrist skeleton occurred in the epiphyseal ossification centers of the middle phalangeal bone in the second, third, and fourth finger and in the distal phalangeal bone in the fifth finger. The epiphyseal ossification centers were lacking in the middle and distal phalangeal bones of the fifth finger.. The underlying gene defect in the affected children seemingly affects bone development and growth but not dental maturation and eruption.

Topics: Adolescent; Age Determination by Skeleton; Anodontia; Bone Development; Cephalometry; Child; Chin; Craniofacial Abnormalities; Epiphyses; Female; Fingers; Growth Disorders; Humans; Intellectual Disability; Male; Maxilla; Microcephaly; Nose; Odontogenesis; Sella Turcica; Skull Base; Syndrome; Tooth Abnormalities; Tooth Root; Wrist

We report a Japanese girl with brachycephaly, a wide forehead, hypertelorism, macroblepharon with eyelid colobomas, ectropion, a broad nasal root, a depressed nasal tip, macrostomia, a small and grooved chin, ear anomalies, a structural anomaly of the corpus callosum, dilatation of the fourth ventricle, a urogenital sinus, and mental retardation. Cause and inheritance are unknown.

Topics: Abnormalities, Multiple; Brain; Child, Preschool; Ear; Eyelids; Female; Humans; Intellectual Disability; Macrostomia; Nose

We describe the clinical findings and natural history in two unrelated deeply mentally retarded females, now 28 and 20 years old respectively. Both presented prenatal growth retardation and severe postnatal growth retardation. Their craniofacial appearance is distinct with nasal hypoplasia, triangular mouth and thin lips. Both have a cleft palate and a retinal coloboma at the right eye. Motor development is below the age of 1 year with a complex neurological syndrome with axial hypotonia and spastic quadriplegia.

Topics: Abnormalities, Multiple; Cleft Palate; Coloboma; Craniofacial Abnormalities; Facies; Female; Growth Disorders; Humans; Intellectual Disability; Nose; Retina; Syndrome

We report on four unrelated Brazilian patients with growth and mental retardation, structural anomalies of the central nervous system (CNS), mainly callosal agenesis, prominent forehead, facial asymmetry, anophthalmia, heminasal a/hypoplasia, preauricular skin tags, structural anomalies of the external ears, and atypical clefting. This combination of anomalies is unique and, to our knowledge, is a previously undescribed syndrome of unknown etiology, although one of the patients was born to a consanguineous couple, suggesting the possibility of autosomal recessive inheritance. Clinical, genetic, and differential diagnosis aspects are discussed.

Topics: Abnormalities, Multiple; Agenesis of Corpus Callosum; Anophthalmos; Branchial Region; Brazil; Central Nervous System; Cleft Lip; Consanguinity; Dwarfism; Encephalocele; Female; Humans; Infant, Newborn; Intellectual Disability; Magnetic Resonance Imaging; Male; Nose; Phenotype; Syndrome

Blepharo-naso-facial syndrome, described by Pashayan et al. (10), is characterized by telecanthus, lateral displacement and stenosis of lacrimal puncta, bulky nose, mask-like facies, trapezoïdal upper lip, torsion dystonia and mental retardation. We report on a family with this rare malformation syndrome, confirming the existence of this syndrome and its dominant inheritance. The proband had a fleshy nose, a prominant nose bridge, an hypoplastic midface, telecanthus with temporal displacement of puncta, lacrimal excretory obstruction. CNS torsion dystonia, increased deep tendon reflexes, Babinski reflexes, poor coordination and joint laxity. The proband's mother, brother and maternal grandfather also showed manifestations of the syndrome. The proband and his brother had delayed developmental milestones. Hearing impairment was present in the proband, his mother and his grandfather but was absent in the proband's brother. The blepharonasofacial syndrome was described by Pashayan et al. (10) in four members of one family, two male and one female sib and their mother. Two other sibs were unaffected. Many of the features of the blepharo-facio-nasal syndrome also occur in other well known syndromes i.e. Waardenburg syndrome. The pedigrees of the family of Pashayan et al. (10) and of our family are compatible with Mendelian dominant inheritance, either autosomal or X-linked. X-linked dominant inheritance cannot be ruled out except by male-to-male transmission, which does not occur in these families. Pashayan et al. (10) suggested that an autosomal gene with variable expressivity appears more likely. More families are needed for defining the transmission of the condition and for mapping the gene involved in the blepharo-naso-facial syndrome.

Topics: Abnormalities, Multiple; Adolescent; Craniofacial Abnormalities; Eye Abnormalities; Female; Humans; Infant; Intellectual Disability; Male; Nose; Pedigree; Syndrome; Waardenburg Syndrome

Topics: Child, Preschool; Craniofacial Abnormalities; Developmental Disabilities; Dwarfism; Follow-Up Studies; Humans; Infant; Infant, Newborn; Intellectual Disability; Male; Muscle Hypotonia; Nose; Paraplegia; Syndrome

A single maxillary central incisor in the midline is a rare developmental anomaly. The appearance of a single incisor in place of two teeth may occur as an isolated dental finding that can be related to fusion of two neighboring teeth or to agenesis of a tooth germ. However, the condition has also been reported to occur in association with autosomal dominant holoprosencephaly, growth retardation, and midline developmental defects. This article reports on other systemic defects that can be found in association with a single maxillary central incisor.

Topics: Anodontia; Child; Cryptorchidism; Disease; Dwarfism; Human Growth Hormone; Humans; Incisor; Intellectual Disability; Male; Maxilla; Nasal Septum; Nose

Bilateral periventricular nodular heterotopia (BPNH) is a recently recognized malformation of neuronal migration in which nodular masses of gray matter line the walls of the lateral ventricles. Most affected individuals are females with epilepsy and normal intelligence, but no other congenital anomalies. Studies in families with multiple affected individuals, always all females, have mapped one BPNH gene to chromosome Xq28. Several other BPNH syndromes associated with mental retardation and epilepsy but without significant dysmorphic facial features have been observed in males only, which may also be X-linked. This report describes a new syndrome with BPNH.. Clinical and MRI study and cognitive testing of two unrelated boys, aged 8 and 5.5 years, and review of the enlarging spectrum of syndromes associated with BPNH.. Similarities between the two boys are sufficient to delineate a new multiple congenital anomaly-mental retardation syndrome that consists of BPNH, regional cortical dysplasia, mild mental retardation, and frontonasal malformation.. The cause of this unusual syndrome is unknown; based on linkage of other BPNH syndromes to chromosome Xq28 and the report of possible X-linked inheritance of frontonasal malformation, we suspect the cause is genetic, with possible X-linked inheritance.

Topics: Abnormalities, Multiple; Cerebral Ventricles; Child; Child, Preschool; Choristoma; Epilepsy; Frontal Bone; Functional Laterality; Genetic Linkage; Humans; Intellectual Disability; Magnetic Resonance Imaging; Male; Nose; Syndrome; X Chromosome

We describe a boy born to non-consanguineous parents who presents a singular clinical picture characterized by severe mental retardation, craniosynostosis, ocular abnormalities, and frontonasal malformation. This seems to be a previously undescribed condition of unknown aetiology which should be mainly distinguished from craniofrontonasal dysplasia, and frontofacionasal dysostosis.

Topics: Abnormalities, Multiple; Adolescent; Eye Abnormalities; Humans; Intellectual Disability; Male; Nose; Skull

We present a family with six children of first cousin parents, in which three present with microcephaly, hypertelorism, down-slanting palpebral fissures, ptosis, a broad nasal tip, a short webbed neck, mental retardation and seizures. Two differential diagnosis, the Noonan and the Baraitser-Winter syndrome are discussed. The possibility of the description of a new MCA/MR syndrome is raised.

Topics: Abnormalities, Multiple; Astigmatism; Blepharoptosis; Brain; Child; Child, Preschool; Consanguinity; Face; Female; Genes, Recessive; Humans; Hypertelorism; Intellectual Disability; Male; Neck; Nose; Nystagmus, Pathologic; Pedigree; Seizures; Syndrome

Topics: Abnormalities, Multiple; Adult; Cataract; Cuspid; Eye Abnormalities; Face; Female; Heart Defects, Congenital; Humans; Intellectual Disability; Nose; Radiography; Syndrome

Topics: Abnormalities, Multiple; Adult; Brain; Craniosynostoses; Female; Fetal Diseases; Fetal Growth Retardation; Humans; Infant, Newborn; Intellectual Disability; Male; Microcephaly; Micrognathism; Nose; Pregnancy; Syndrome; Ultrasonography, Prenatal

Aerodynamic and acoustic characteristics were determined from the speech of an adult female with mild mental retardation and severe velopharyngeal inadequacy. The speaker's productions of /s/ were characterized by consistent nasal grimacing and turbulent air emission. Aerodynamic assessment estimated the size of the velopharyngeal orifice to exceed 200 mm2 during plosive production. Nasal cross-sectional area was estimated to be 35 mm2 during quiet breathing. Nasometric evaluation indicated nasalance of 63% associated with the "Zoo" passage. Acoustic analysis of the separately recorded oral and nasal speech signals indicated spectral energies in the region of approximately 2.5 to 7.0 kHz associated with nasal emission during /s/ production. The occurrence of these frequencies suggested an acoustic/perceptual function of the nasal grimace. Pressure-flow evidence also suggested that the nasal grimace, perhaps with lingual assistance, functioned to enhance speech aerodynamics.

Topics: Adult; Air Pressure; Airway Resistance; Articulation Disorders; Female; Humans; Intellectual Disability; Nose; Pulmonary Ventilation; Sound Spectrography; Speech Production Measurement; Velopharyngeal Insufficiency; Voice Quality

In this report we describe two unrelated young males with severe mental retardation, persisting hypotonia, and constipation. A maternal uncle of one of these two boys died at the age of 18 months and presented the same clinical symptoms. The triad mental retardation, hypotonia, constipation is a characteristic finding in the FG syndrome, an X-linked mental retardation syndrome. At the present time, there is increasing evidence that the FG syndrome-phenotype may be present in different XLMR conditions, e.g. the fragile X syndrome. In addition to the triad severe mental retardation, hypotonia, constipation, the present two male index patients had a characteristic facial appearance with nasal hypoplasia, relative microcephaly and pre- and postnatal overgrowth. The question is raised whether the present two males are examples of a specific entity within the FG-syndrome-like phenotype.

Topics: Abnormalities, Multiple; Child, Preschool; Constipation; Face; Growth; Humans; Intellectual Disability; Male; Microcephaly; Muscle Hypotonia; Nose; Syndrome

Craniofrontonasal dysplasia: more severe expression in the mother than in her son: We report a family with craniofrontonasal dysplasia in a mother and her son. In addition to the typical clinical features, the present case report further illustrates two sofar unexplained observations in craniofrontonasal dysplasia: a more severe clinical expression in females and an increased incidence of miscarriages.

Topics: Abnormalities, Multiple; Adult; Child, Preschool; Facial Bones; Female; Genetic Carrier Screening; Genetic Counseling; Humans; Intellectual Disability; Male; Nose; Phenotype; Skull

A 22 year old woman with partial trisomy for the long arm of chromosome 2 is described. The karyotype is 46,XX, dir dup(2)(q33.1q35) de novo confirmed by FISH using a chromosome 2 specific paint. Parental chromosome studies were normal. To our knowledge this is the first report of trisomy for this specific segment of 2q and only the sixth case of de novo direct duplication of 2q, one of which was mosaic. Clinical features include epicanthus, clinodactyly, scoliosis, broad, flat nasal bridge, thin upper lip, long philtrum, and short neck.

Topics: Abnormalities, Multiple; Adult; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, Pair 2; Eyelids; Female; Humans; Intellectual Disability; Nose; Scoliosis; Trisomy

We report on 2 unrelated Brazilian girls, born to nonconsanguineous parents, and presenting structural central nervous system defects, hydrocephaly, macrocephaly, craniosynostosis, prominent forehead, anophthalmia, and abnormal nares. These patients may have a previously undescribed recurrent-pattern cerebro-oculo-nasal syndrome.

Topics: Abnormalities, Multiple; Anophthalmos; Brain; Brazil; Cerebral Ventricles; Child, Preschool; Female; Humans; Infant; Intellectual Disability; Nose; Phenotype; Syndrome; Tooth Abnormalities

A patient with median cleft lip is reported, but the patient showed no evidence of holoprosencephaly, which was ruled out by MRI. When the neonate's head circumference is within two standard deviations of the mean and normotelorism occurs with median cleft lip, it can be assumed that the brain is not holoprosencephalic. The importance of this cannot be overemphasized because median cleft lip is commonly associated with holoprosencephaly and severe microcephaly. The mother developed overt diabetes mellitus after the patient was born. However, infants of diabetic mothers are known to be at increased risk of giving birth to infants with holoprosencephaly. Since a prediabetic woman may sometimes give birth to large and/or malformed infants before developing overt diabetes mellitus, it is intriguing to speculate that the prediabetic state might have resulted in a forme fruste of holoprosencephaly, affecting, in this case, only the face and not the brain.

Topics: Anodontia; Cleft Lip; Cleft Palate; Female; Follow-Up Studies; Holoprosencephaly; Humans; Infant, Newborn; Intellectual Disability; Male; Nose; Prediabetic State; Pregnancy; Pregnancy in Diabetics

A 4 year old girl is described with severe mental retardation, peculiar face with nasal hypoplasia, sparse hair, genital hypoplasia, truncal obesity, puffy hands, and small feet with complete cutaneous syndactyly of the second and third toes.

Topics: Abnormalities, Multiple; Child, Preschool; Face; Female; Genitalia, Female; Hair; Humans; Intellectual Disability; Nose; Syndrome; Toes

Topics: Abnormalities, Multiple; Blepharoptosis; Child, Preschool; Coloboma; Humans; Infant; Infant, Newborn; Intellectual Disability; Karyotyping; Male; Nose; Pedigree; Phenotype

We report on a sister and brother with severe mental retardation, bulbous tip of the nose, long columella, cleft lip and palate, heart and intestinal anomalies, and growth retardation. This appears to be a previously unreported, autosomal recessive condition, given high resolution prometaphase chromosomes are normal.

Topics: Abnormalities, Multiple; Child; Female; Genes, Recessive; Heart Defects, Congenital; Humans; Infant; Intellectual Disability; Iris; Male; Nose; Syndrome

We describe the seventh patient with the Floating-Harbor syndrome. Similar to previous cases in the literature this girl presented with proportionate intrauterine and postnatal growth retardation, normocephaly, triangular face with bulbous nose, long eyelashes, short upper lip, small vermilion border of upper lip, dorsally rotated ears, deep nuchal hair line, hirsutism, and clinodactyly of little fingers. She exhibited mental retardation and retarded speech development. Clinical symptoms and differential diagnosis of this rare syndrome are briefly discussed.

Topics: Abnormalities, Multiple; Child; Diagnosis, Differential; Eye Abnormalities; Female; Fetal Growth Retardation; Fingers; Growth Disorders; Hirsutism; Humans; Intellectual Disability; Mouth Abnormalities; Nose; Syndrome

Topics: Abnormalities, Multiple; Child, Preschool; Consanguinity; Female; Humans; Infant; Intellectual Disability; Macrostomia; Male; Micrognathism; Muscle Hypotonia; Nose; Skull

Kabuki make-up syndrome (Niikawa-Kuroki syndrome), recognized in Japan in 1981, is characterized by mental and growth retardation with specific craniofacial malformation such as lower palpebral eversion and depressed nasal tip. In this paper we describe a case associated with cleft lip and palate. Attention should be paid by maxillofacial surgeons to this syndrome, since 41% of the cases have been associated with cleft lip and palate (Niikawa et al., 1988; Tonoki and Niikawa, 1988).

Topics: Cleft Lip; Cleft Palate; Eyebrows; Eyelids; Female; Humans; Infant; Infant, Newborn; Intellectual Disability; Nose; Syndrome

A case of Laband syndrome in an 8-yr-old girl is presented. The case is sporadic. The patient manifests enlargement of the soft tissue of the hard palate and the gingiva, which partly or completely covers the crowns of the teeth and macroglossia. The cartilagenous part of the nose and the ears is large and soft. She has synophrys and thick, straight hair. The nails of the fingers and toes are dysplastic. The girl exhibits no other abnormality, except an IQ of 61.

Topics: Abnormalities, Multiple; Child; Female; Fibromatosis, Gingival; Humans; Intellectual Disability; Macroglossia; Nails, Malformed; Nose; Syndrome

We report a 19-year-old boy with an interstitial deletion of the long arm of chromosome 8 (46, XY, del(8)(pter----q23.3: :q24.13----qter)). He shows the typical clinical symptoms of tricho-rhino-phalangeal syndrome (TRPI) and severe mental retardation, however without multiple exostoses. This is the second report of a combination of abnormalities and interstitial deletion of 8q.

Topics: Adult; Chromosome Deletion; Chromosomes, Human, Pair 8; Foot Deformities, Congenital; Hand Deformities, Congenital; Humans; Hypotrichosis; Intellectual Disability; Male; Nose; Syndrome

Here we report on a 13-year-old boy who had an interstitial deletion of the long arm of chromosome 8 [46,XY,del(8)(pter----q23.3::q24.13----qter)]. He had the facial features of the tricho-rhino-phalangeal (TRP) syndrome and severe mental retardation, but lacked multiple exostoses. This is the first report with such a peculiar combination of abnormalities and interstitial deletion of 8q.

Topics: Chromosome Banding; Chromosome Deletion; Chromosomes, Human, Pair 8; Exostoses, Multiple Hereditary; Facial Expression; Fingers; Hair; Humans; Infant, Newborn; Intellectual Disability; Male; Nose; Phenotype; Syndrome

Topics: Abnormalities, Multiple; Child, Preschool; Deafness; Humans; Hypopituitarism; Intellectual Disability; Male; Nose; Syndrome

A case of oculodentodigital dysplasia in a 35-year-old man is reported. The diagnosis was based on the characteristic facies, microcornea, and dental dysplasia. Digital findings, although consistent with previous reports, were somewhat atypical, with almost complete aplasia of the right foot present. Although the patient appeared to be mentally retarded, it is not clear whether this can be considered a component of the syndrome or merely a coincidental finding.

Topics: Adult; Dental Enamel Hypoplasia; Fingers; Humans; Intellectual Disability; Male; Nose; Syndrome; Toes

We describe two sibs born to a consanguineous couple. Among other clinical findings both have mental retardation, short stature, facial and skeletal abnormalities characterized by hypertelorism, broad notched nasal tip, cleft lip/palate, campto-brachy-poly-syndactyly, fibular hypoplasia, and marked anomalies of foot structures. Facial signs of the reported patients resemble those present in the fronto-nasal "dysplasia" syndrome; however, the whole clinical picture in the present patients suggests a true MCA/MR syndrome, most likely inherited as an autosomal recessive trait. Clinical and genetic aspects of the present family are discussed.

Topics: Abnormalities, Multiple; Child; Cleft Lip; Cleft Palate; Consanguinity; Dermatoglyphics; Facial Bones; Female; Foot Deformities, Congenital; Genes, Recessive; Humans; Intellectual Disability; Male; Nose; Osteochondrodysplasias; Skull; Syndactyly

Two persons within the same family were discovered to be trisomic for the segment 7qter. However, several features differed from those described in other patients with this syndrome, for example, normal birth weight and neck size, cleft palate, and beaked nose. In addition to the phenotypic variation, there were three independently segregating autosomal translocations in the pedigree: t(1;7)(q43;q32), t(1;6) (p22.3;q14.1), and t(3;10)(q26.1;p11.21). This is a finding that, to our knowledge, has not been previously reported.

Topics: Adult; Birth Weight; Chromosome Banding; Chromosomes, Human, 1-3; Chromosomes, Human, 6-12 and X; Cleft Palate; Female; Humans; Infant, Newborn; Intellectual Disability; Karyotyping; Male; Nose; Pedigree; Phenotype; Syndrome; Translocation, Genetic; Trisomy

We report a boy with a trichorhinophalangeal syndrome (TRP syndrome), severe mental retardation, and transient megacephaly, whose karyotype showed complex, apparently balanced, translocations with breakpoints in bands 3q13, 8p22, 8q13, 11p12, and 11q21. The fact that cases presenting with phenotypes corresponding to the TRP II syndrome and deletions of the long arm of chromosome 8 have been recently reported prompted us to report this case to help in the clarification of the possible relation between 8q chromosomal mutation and the aetiology of TRP syndromes.

Topics: Abnormalities, Multiple; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, 1-3; Chromosomes, Human, 21-22 and Y; Chromosomes, Human, 6-12 and X; Humans; Intellectual Disability; Karyotyping; Male; Nose; Syndrome; Translocation, Genetic

Topics: Abnormalities, Multiple; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, 13-15; Genitalia, Male; Humans; Infant; Intellectual Disability; Limb Deformities, Congenital; Male; Microcephaly; Nose; Syndactyly; Syndrome; Trisomy

Topics: Adult; Eye Abnormalities; Face; Female; Hand Deformities, Congenital; Humans; Hypertelorism; Infant, Newborn; Intellectual Disability; Nose; Skull; Syndrome

We describe a 12-year-old girl with Langer-Giedion syndrome (tricho-rhino-phalangeal syndrome type II) who also had vertebral malformations. Chromosome analysis identified an interstitial del(8q): 46,XX,del(8)(pter leads to q22::q234 leads to qter) as a cause of this syndrome.

Topics: Abnormalities, Multiple; Bone and Bones; Child; Chromosome Aberrations; Chromosome Banding; Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, 6-12 and X; Female; Fingers; Humans; Intellectual Disability; Karyotyping; Nose; Spine; Syndrome

Topics: Child; Epilepsy; Female; Genes, Recessive; Humans; Intellectual Disability; Male; Nose; Pedigree; Syndrome

A child with terminal deletion of the long arm of the Y chromosome (Yq--) presented with marked livedo reticularis, snub nose, microcephaly, short stature, and other dysmorphic features. He was profoundly mentally retarded. Most of the patients with Yq- have been reported as having varying dysmorphic features, mental retardation, and short stature. This child, in addition to the above, has livedo reticularis and microcephaly. He was of normal birthweight and, therefore, does not come into the syndrome of microcephaly, snub nose, livedo reticularis, and low birthweight dwarfism. Further information on Yq- should be obtained to ascertain if consistent patterns of abnormalities exist.

Topics: Body Height; Child; Chromosome Deletion; Humans; Intellectual Disability; Karyotyping; Male; Microcephaly; Nose; Sex Chromosome Aberrations; Vascular Diseases; Y Chromosome

This article reports on 14 cases of a trichorhinophalangeal syndrome in five successive generations. Besides the well-known characteristics of the TRPS the following symptoms observed in this family are new: Teething was considerably delayed, intelligence was reduced, and there were skin manifestations resembling eczema. Besides, struma colli and colitis ulcerosa were also observed. Subsequent observations have to clarify whether these symptoms are a facultative part of the TRPS pattern. The constant appearance of carriers of these characteristics during five generations points to dominant heredity.

Topics: Abnormalities, Multiple; Adolescent; Adult; Aged; Child; Colitis, Ulcerative; Eczema; Female; Fingers; Goiter; Hair; Heterozygote; Humans; Intellectual Disability; Male; Middle Aged; Nose; Pedigree; Radiography; Syndrome

Two cases, a father and daughter, with all the principal signs of tricho-rhino-phalangeal syndrome Type II are described, although nine previously reported cases were all sporadic. It is suggested that these patients have a genetic disorder with an autosomal dominant mode of inheritance. It may be reasonable to assume that a patient with relatively mild mental retardation, such as the father in the present report, could marry and have off-spring. Generalized aminoaciduria was found in the affected daughter.

Topics: Abnormalities, Multiple; Adult; Child; Exostoses, Multiple Hereditary; Female; Fingers; Hair; Humans; Intellectual Disability; Male; Nose; Pedigree; Radiography; Syndrome

Five unrelated patients with a previously unrecognized mental retardation malformation syndrome are presented. Clinical features common to them include moderate mental retardation, postnatal dwarfism, susceptibility to infection in infancy, and peculiar craniofacial dysmorphia characterized by long palpebral fissures, high-arched and abnormal eyebrows, heavy and long eyelashes, large ears, short nasal septum and/or depressed nasal tip, and cleft palate. Other anomalies are stubby fingers, deformed vertebra and other bone and joint anomalies, and abnormal dermatoglyphics. The absence of familial occurrence and of consanguinity suggests some environmental causation, but the possibility of an autosomal dominant or X-linked mode of inheritance remains. Based upon our five patients and other five of Niikawa et al, we propose this syndrome as a new disease entity.

Topics: Abnormalities, Multiple; Adolescent; Bone and Bones; Child; Child, Preschool; Dwarfism; Ear, External; Eyelids; Face; Female; Humans; Infant; Intellectual Disability; Male; Nose; Syndrome

Topics: Brain; Child, Preschool; Facial Bones; Female; Frontal Bone; Humans; Intellectual Disability; Nose

We have evaluated a sister and brother with a similar pattern of malformations and death in early childhood associated with partial duplication chromosome 5p and possibly deletion of 9p. The father and the brother and several paternal relatives are carriers of the balanced translocation t(5;9) (p13;p22). The malformations which the two have in common are: prominent forehead, flat nasal bridge, long thin fingers, bilateral equinovarus deformity of the feet, diaphragmatic hernia and kidney malformations. The children died at ages 4 months and 27 months, the latter showing marked psychomotor retardation. The chromosome abnormalities, clinical history, and phenotypic features of our patients are similar to the case reported by Monteleone et al (1976). The findings in our patients and Monteleone et al. (1976) are not similar to those in other reported cases of partial and complete 5q duplications, perhaps because the others do not have partial deletion of 9p.

Topics: Abnormalities, Multiple; Chromosome Aberrations; Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, 4-5; Chromosomes, Human, 6-12 and X; Female; Fingers; Humans; Infant; Intellectual Disability; Male; Nose; Pedigree; Psychomotor Disorders

Topics: Abnormalities, Multiple; Adult; Cerebral Aqueduct; Fingers; Hair; Humans; Intellectual Disability; Male; Nose; Syndrome

A 14-month-old female with the Coffin-Siris syndrome is described. Typical features included underweight at birth, growth retardation, microcephaly, profound mental retardation, severe hypotonia with lax joints, feeding difficulties and frequent respiratory tract infections; sparce scalp hair, small nose, epicanthic folds, a prominent philtrum and full lips; a congenital heart defect; hypoplasia or aplasia of the distal phalanges of digits 2--5 and the corresponding nails, especially of the fifth fingers and toes, and aplasia of the middle phalanges of the little fingers and the second and fifth toes; severe delay in bone maturation. The proposita also showed hypoplasia of the lateral portions of both clavicles. Inheritance of the Coffin-Siris syndrome is possibly autosomal recessive.

Topics: Abnormalities, Multiple; Cardiomegaly; Face; Female; Fingers; Genes, Recessive; Growth Disorders; Hair; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Intellectual Disability; Lip; Microcephaly; Nails, Malformed; Nose; Radiography; Respiratory Tract Infections; Syndrome; Toes

Topics: Abnormalities, Multiple; Child; Exostoses, Multiple Hereditary; Hand Deformities, Congenital; Humans; Hypotrichosis; Intellectual Disability; Male; Nose; Syndrome

Topics: Bone Diseases, Developmental; Eye Color; Genes, Dominant; Humans; Intellectual Disability; Nose; Syndrome

We report the case of a boy with the Johanson-Blizzard syndrome who died at the age of 8 years with complications of pancreatic exocrine insufficiency, and at autopsy was found to have a small thyroid filled with colloid, virtually complete replacement of the pancreas with adipose tissue, and a brain of normal size but with evidence of a cortical developmental defect consisting of abnormalities of gyral formation and of cortical neuronal organization. In addition the boy had postnatal growth failure, apparent severe mental retardation, congenital scalp defects and scalp hair patterning abnormalities, aplasia of the nasal alae, nasolacrimo-cutaneous fistulae, hypotonia, severe congenital sensorineural deafness, and small conical and widely spaced teeth. Evidence is accumulating that this syndrome is likely to be inherited as an autosomal recessive disorder. Our case represents the first report of autopsy findings in the syndrome.

Topics: Abnormalities, Multiple; Adipose Tissue; Child; Genes, Recessive; Humans; Hypothyroidism; Intellectual Disability; Malabsorption Syndromes; Male; Nose; Pancreas; Pancreatic Diseases; Syndrome

Acrodysostosis--a rare congenital malformation syndrome--is described in a 4 1/2 year old boy with peripheral dysostosis, nasal hypoplasia, mental retardation (PNM syndrome) and impaired hearing. The differential diagnosis includes pseudo (PH)--and pseudo-pseudohypoparathyroidism (PPH). The patient described here had severe peripheral dysostosis, typical of PNM as opposed to the above-mentioned conditions with only moderate peripheral dysostosis. Furthermore, there were no soft tissue calcifications and no intracranial calcification as can be seen in PH and PPH. Laboratory findings were normal.

Topics: Bone Diseases, Developmental; Child, Preschool; Hearing Disorders; Humans; Intellectual Disability; Male; Nose; Radiography; Syndrome

Two Japanese siblings, a 2-year-old girl and a 7-month-old boy, had a syndrome of mental retardation, severe nasal hyp9plasia, peripheral dysostosis, and blue eyes. The mother showed nasal hyp9plasia of lesser degree and a mild form of peripheral dysostosis. This disorder bears a striking similarity to acrodysostosis, but in view of certain novel features its relationship to the disease is uncertain. The mode of inheritance could be either dominant with variable expressivity or autosomal recessive.

Topics: Bone Diseases, Developmental; Child, Preschool; Eye Color; Female; Humans; Infant; Intellectual Disability; Male; Nose; Pedigree; Phenotype; Syndrome

An infant with aplastic alae nasi, imperforate anus, focal aplasia cutis over the fontanels, microcephaly, and mental retardation is presented as an example of the Johanson-Blizzard syndrome. The infant failed to thrive and had evidence of malabsorption. He died at 4 months of age. The occurrence of extensive consanguinity in his family and the occurrence of two other members of the kindred with a similar syndrome indicate that this disorder is transmitted by an autosomal recessive gene.

Topics: Abnormalities, Multiple; Anus, Imperforate; Chromosome Aberrations; Chromosome Disorders; Consanguinity; Genes, Recessive; Humans; Infant; Intellectual Disability; Male; Nose; Pedigree; Skin Abnormalities; Syndrome

Topics: Abnormalities, Multiple; Child; Electroencephalography; Female; Humans; Hyperventilation; Intellectual Disability; Macrostomia; Male; Nose; Osteoarthropathy, Secondary Hypertrophic; Syndrome

Topics: Adult; Child; Cleft Lip; Coloboma; Female; Genes, Dominant; Humans; Infant; Intellectual Disability; Male; Microcephaly; Nose; Pedigree; Syndrome

Topics: Deafness; Dwarfism; Hair; Humans; Infant; Infant, Newborn; Intellectual Disability; Malabsorption Syndromes; Male; Nose; Phenotype; Skin Abnormalities; Syndrome; Tooth Abnormalities

A child with nasal hypoplasia, growth and developmental delay, and 18p--due to 14q/18q apparent dicentric fusion is reported. Review of ten previously reported patients with 18p--due to fusion translocations involving the long arm of chromosome 18 reveals clinical features ranging from arrhinencephaly to minimal dysmorphic changes and mild retardation. This spectrum of clinical expression is similar to that seen in patients with partial 18p deletions. Since the same range of clinical features is observed whether there is partial or apparent total deletion of 18p, it is suggested that only a distal segment of the short arm of chromosome 18 may be etiologically related to the clinical phenotype in the 18p--syndrome.

Topics: Child, Preschool; Chromosomes, Human, 13-15; Chromosomes, Human, 16-18; Dermatoglyphics; Humans; Intellectual Disability; Karyotyping; Male; Nose; Phenotype; Translocation, Genetic

Topics: Abnormalities, Multiple; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, 16-18; Craniofacial Dysostosis; Ear, External; Humans; Infant; Infant, Newborn; Intellectual Disability; Karyotyping; Male; Nose; Palate; Thumb; Trisomy

Topics: Abnormalities, Multiple; Adolescent; Bone Diseases, Developmental; Child; Diagnosis, Differential; Ear, External; Face; Facial Expression; Female; Fingers; Hair; Humans; Intellectual Disability; Male; Nose; Syndrome; Toes

Topics: Abnormalities, Multiple; Adult; Chromosome Aberrations; Chromosome Disorders; Chromosome Mapping; Chromosomes, Human, 21-22 and Y; Craniofacial Dysostosis; Dermatoglyphics; Female; Fibroblasts; Humans; Hypertension; Infant, Newborn; Intellectual Disability; Karyotyping; Lymphocytes; Male; Micrognathism; Microphthalmos; Microscopy, Fluorescence; Nose; Palate; Pregnancy; Quinacrine; Skin; Skull; Syndrome

Topics: Abnormalities, Multiple; Adolescent; Clitoris; Congenital Hypothyroidism; Deafness; Disorders of Sex Development; Dwarfism; Ectodermal Dysplasia; Female; Humans; Intellectual Disability; Male; Nose; Pancreatic Diseases; Urethra; Uterus; Vagina

Topics: Abnormalities, Multiple; Adult; Cataract Extraction; Child; Disorders of Sex Development; Female; Growth Disorders; Humans; Intellectual Disability; Male; Microcephaly; Nose; Pyloric Stenosis; Syndactyly; Toes

Topics: Abnormalities, Multiple; Adolescent; Ear; Face; Humans; Intellectual Disability; Mouth Abnormalities; Nose

Topics: Abnormalities, Multiple; Birth Weight; Child; Child, Preschool; Congenital Hypothyroidism; Deafness; Dwarfism; Ectodermal Dysplasia; Female; Humans; Intellectual Disability; Malabsorption Syndromes; Nose; Nose Deformities, Acquired; Tooth Abnormalities

Topics: Body Weight; Child; Child, Preschool; Dwarfism; Female; Fingers; Humans; Intellectual Disability; Male; Mouth; Nails, Malformed; Nose; Toes

Topics: Abnormalities, Multiple; Adolescent; Child, Preschool; Cleft Lip; Cleft Palate; Craniofacial Dysostosis; Craniosynostoses; Dermoid Cyst; Encephalocele; Eye Neoplasms; Eyelids; Face; Female; Humans; Infant; Infant, Newborn; Intellectual Disability; Limb Deformities, Congenital; Micrognathism; Microphthalmos; Nose; Strabismus

Topics: Abnormalities, Multiple; Autoradiography; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, 4-5; Cleft Palate; Growth; Growth Disorders; Humans; Infant; Intellectual Disability; Iris; Karyotyping; Male; Nose

Topics: Aged; Calculi; Female; Foreign Bodies; Humans; Intellectual Disability; Nose; Palate; Ulcer

Topics: Abnormalities, Multiple; Adolescent; Blood Cells; Child; Deafness; Diseases in Twins; Eye Diseases; Eyebrows; Face; Female; Foot Deformities, Congenital; Genes, Dominant; Hand Deformities, Congenital; Humans; Intellectual Disability; Iris; Karyotyping; Keratosis; Male; Middle Aged; Nose; Pedigree; Pigmentation Disorders; Waardenburg Syndrome

Topics: Child; Child, Preschool; Congenital Abnormalities; Dental Enamel Hypoplasia; Eye Abnormalities; Female; Humans; Infant; Intellectual Disability; Male; Nose; Orofaciodigital Syndromes

Topics: Congenital Abnormalities; Disorder of Sex Development, 46,XY; Disorders of Sex Development; Eye Manifestations; Face; Facial Expression; Female; Foot Diseases; Genetics, Medical; Hand Deformities; Humans; Hypospadias; Infant; Infant, Newborn; Intellectual Disability; Jaw; Male; Microcephaly; Movement Disorders; Nose; Nose Deformities, Acquired; Pyloric Stenosis; Retrognathia; Skin Manifestations; Strabismus

Topics: Anodontia; Child; Ear Deformities, Acquired; Ear, External; Ectodermal Dysplasia; Genetics, Medical; Hair; Humans; Intellectual Disability; Nose; Nose Deformities, Acquired; Respiratory Tract Infections; Sweating; Xerophthalmia

Topics: Cerebral Ventriculography; Child; Dental Enamel Hypoplasia; Electroencephalography; Epilepsy; Eye Abnormalities; Female; Fingers; Glaucoma; Hair; Humans; Intellectual Disability; Iris; Microphthalmos; Nose; Radiography; Toes; Tooth Discoloration

Topics: Adolescent; Amelogenesis Imperfecta; Cleft Palate; Congenital Abnormalities; Craniofacial Dysostosis; Dental Occlusion; Dentures; Face; Female; Fingers; Hair; Humans; Intellectual Disability; Maxillofacial Development; Models, Dental; Nails; Nose; Orofaciodigital Syndromes; Orthodontics, Corrective; Toes

Topics: Child; Clioquinol; Down Syndrome; Drug Resistance; Drug Resistance, Microbial; Drug Therapy; Enterobacter aerogenes; Escherichia coli; Fungi; Humans; Intellectual Disability; Intestines; Nose; Pharynx; Pseudomonas aeruginosa; Rectum; Streptococcus; Streptococcus pyogenes

Three cases of de Lange's syndrome are described. This condition is characterized by generally severe mental retardation, reduced stature, mild microcephaly, hypertrichosis, various anomalies of hands and feet, and a peculiar facies. The most outstanding features of the latter are the low forehead, profuse, generally confluent eyebrows, abundant long eyelashes, eyes that frequently slant downwards and outwards in antimongoloid fashion, pug nose with prominent anteverted nostrils, increased distance between nose and vermilion border of upper lip, slight reduction in size of chin, and often abnormally low-placed ears. The etiology of de Lange's syndrome is at present unknown.

Topics: Adolescent; Body Height; Child; Congenital Abnormalities; De Lange Syndrome; Ear Deformities, Acquired; Ear, External; Eye; Eyebrows; Facial Expression; Hand Deformities; Hirsutism; Humans; Hypertrichosis; Intellectual Disability; Lip; Mandible; Microcephaly; Nose; Nose Deformities, Acquired

Topics: Facial Dermatoses; Humans; Hyperhidrosis; Intellectual Disability; Nose; Nose Diseases; Skin Diseases, Papulosquamous