phenylephrine-hydrochloride and Developmental-Disabilities

Topics: Abnormalities, Multiple; Child; Developmental Disabilities; Diagnosis, Differential; Female; Genetic Diseases, X-Linked; Humans; Hypothyroidism; Mutation; Nose; Prognosis; Scalp; Syndrome; Tooth Loss; Ubiquitin-Protein Ligases

Interstitial deletions of the proximal long arm of chromosome 3 are rare. Only eight previously reported patients have deletions involving the proximal segment of 3q. Of these patients, three had agenesis of the corpus callosum and one had holoprosencephaly. We report here a patient with a small unique interstitial deletion of the long arm of chromosome 3 spanning 3q13.1q13.3. This patient has agenesis of the corpus callosum, global developmental delay, and distinctive facial features of a small nose, anteverted nares, and broad nasal root. Our patient provides further evidence that a gene involved in corpus callosum development or neuronal migration may reside in this region.

Topics: Agenesis of Corpus Callosum; Child, Preschool; Chromosome Banding; Chromosome Deletion; Chromosomes, Human, Pair 3; Developmental Disabilities; Diseases in Twins; Female; Humans; Infant; Infant, Newborn; Nose; Phenotype; Twins, Dizygotic

We report a patient with partial tetrasomy 9q resulting from a de novo triplication of 9q13q22.1. The clinical features, including microcephaly, beaked nose, short palpebral fissures, camptodactyly, joint contractures, and moderate developmental delay were similar to trisomy 9q, although our patient also had unique features including cleft palate and several unexplained fractures. The latter could be secondary to abnormal tone and contractures. Although tetrasomy 9p is a well-known entity, our patient, to our knowledge, is the first and only individual reported to have tetrasomy 9q.

Topics: Abnormalities, Multiple; Aneuploidy; Chromosome Banding; Chromosomes, Human, Pair 9; Cleft Palate; Developmental Disabilities; Hand Deformities, Congenital; Humans; Infant; Karyotyping; Male; Microcephaly; Nose

With improved cytogenetic techniques, small deletions and duplications are being identified with increased frequency. We report four cases with terminal deletions involving the 6p24- and 6p25-pter chromosomal segment who exhibit a distinct, recognizable pattern of malformations including hypertelorism, downslanting palpebral fissures, flat nasal bridge, Dandy-Walker malformation/variant, congenital heart defects, anterior eye-chamber abnormalities, hearing loss, and developmental delay. We also compare the clinical aspects of these patients to those of previously reported cases in the literature with similar terminal deletions of chromosome 6p. Routine chromosome analysis can miss this deletion, therefore, high-resolution chromosome analysis is indicated for individuals who exhibit these distinct features. Furthermore, individuals with this deletion should have an ophthalmologic exam, cardiac evaluation, head imaging, renal ultrasound, and formal hearing evaluation.

Topics: Abnormalities, Multiple; Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 6; Dandy-Walker Syndrome; Developmental Disabilities; Eye Abnormalities; Female; Heart Defects, Congenital; Humans; Hypertelorism; Infant; Nose; Phenotype

We report here a rare case of Möbius-like syndrome associated with a 1;2 chromosome reciprocal translocation (46,XY,t(1;2)(p22.3;q21.1). The patient had facial diplegia, ptosis, anteverted nostrils, malformed and lowset ears, and slight developmental delay. Since a microdeletion could be present at the breakpoint in a reciprocal translocation, it is possible that the gene responsible for Möbius syndrome is located in this region of chromosome 1.

Topics: Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 2; Developmental Disabilities; Ear; Facial Paralysis; Female; Humans; Infant; Male; Nose; Pregnancy; Syndrome; Translocation, Genetic

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

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

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

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

Cerebro-oculo-nasal syndrome (CONS) is characterized by structural anomalies of the central nervous system (encephalocele, ventricular dilatation, defects of corpus callosum, and even holoprosencephaly in one instance), by ocular alterations ranging from anophthalmia/microphthalmia to normal eyes, and by proboscis-like nares. Here, we report on 13 new cases with CONS, review 7 previously published cases, and evaluate the findings in all 20 patients. Despite marked variability among cases, the nasal configuration appears to be unique and diagnostic. Although one patient had a mutation in the PTCH gene, the cause of all other cases remains unknown to date.

Topics: Abnormalities, Multiple; Brain; Brazil; Child; Corpus Callosum; Developmental Disabilities; Eye Abnormalities; Fatal Outcome; Female; Humans; Hypertelorism; Infant; Male; Mutation; Nose

We report a boy with a nasal deformity, choanal atresia, bifid uvula, severe bilateral microphthalmia and a facial cleft who showed regression of development at the age of 2 years with subsequent improvement. We suggest he represents a further case of the rare Fryns "Anophthalmia-Plus" syndrome.

Topics: Abnormalities, Multiple; Anophthalmos; Child, Preschool; Cleft Lip; Cleft Palate; Developmental Disabilities; Humans; Male; Nose

We describe an apparently unique disorder, Fronto-Ocular syndrome, present in a mother and her two daughters, and comprising trigonocephaly due to coronal and metopic craniosynostosis, ocular hypotelorism, ocular proptosis and ptosis, epicanthal folds, hypoplastic supraorbital ridges, elevated nasal bridge, thin philtrum, high-arched palate and a narrow bifrontal region. Both daughters have glabellar capillary hemangiomas, a congenital heart defect and mild developmental disabilities. Review of the literature failed to disclose any syndrome with similar findings. It is likely that this disorder represents an autosomal dominant condition, that arose as a new mutation in the mother. Mutational analysis of fibroblast growth factor receptor (FGFR) 1 and FGFR2 failed to identify the molecular basis of the disorder.

Topics: Adult; Child; Child, Preschool; Craniofacial Abnormalities; Craniosynostoses; Developmental Disabilities; Female; Follow-Up Studies; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Male; Nose; Pedigree; Syndrome

A new case of Hernandez syndrome is described in a 16-year-old Brazilian girl. The syndrome consists mainly of psychomotor retardation, epilepsy, a bulbous nose and obesity.

Topics: Adolescent; Developmental Disabilities; Epilepsy; Female; Humans; Nose; Obesity; Psychomotor Performance; Syndrome

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

We report on two patients with rare 6q duplications. The karyotype of patient 1 is 46,XY,dup(6)(q21q23.3). The karyotype of patient 2 is 46,XX,dup(6)(q21.15q23.3). These two patients have some nonspecific physical findings in common including a depressed nasal bridge, epicanthal folds, mild heart defects, and developmental delay, but each had other congenital anomalies.

Topics: Abnormalities, Multiple; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, Pair 6; Developmental Disabilities; Eyelids; Female; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Karyotyping; Nose

We describe 5 children with midline facial anomalies and iris colobomata reminiscent of frontonasal "dysplasia." Two patients have, in addition, abnormalities of the eyelids and one of them probably has the rare autosomal recessive condition frontofacionasal "dysplasia." The patients may have a new syndrome of midline facial defects, iris colobomata, and mental retardation.

Topics: Abnormalities, Multiple; Adult; Child, Preschool; Coloboma; Developmental Disabilities; Face; Female; Genes, Recessive; Humans; Hypertelorism; Infant; Iris; Male; Nose; Syndrome

We report 21 patients with choanal atresia or ocular coloboma or both who have certain other associated anomalies, including congenital heart disease, postnatal growth deficiency, mental retardation and/or CNS anomalies, microphallus and cryptorchidism, and ear anomalies and/or deafness. Facial palsy, micrognathia, cleft palate, and swallowing difficulties were also common. It has not been possible to define a single etiology or a syndrome in these patients. We propose the mnemonic CHARGE (C-coloboma, H-heart disease, A-atresia choanae, R-retarded growth and retarded development and/or CNS anomalies, G-genital hypoplasia, and E-ear anomalies and/or deafness) to describe the features of this association.

Topics: Abnormalities, Multiple; Adult; Central Nervous System; Coloboma; Deafness; Developmental Disabilities; Ear; Eye Abnormalities; Female; Growth Disorders; Heart Defects, Congenital; Humans; Male; Nasopharynx; Nose; Sexual Dysfunction, Physiological

Topics: Age Factors; Child; Child, Preschool; Deafness; Developmental Disabilities; Hearing Aids; Humans; Infant; Language Development; Motor Skills; Nose; Speech Disorders; Stuttering