phenylephrine-hydrochloride and Eye-Abnormalities

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

Congenital absence of the nose or arhinia is a rare defect of embryogenesis often associated with other anomalies. Arhinia is a life-threatening condition that requires a highly skilled neonatal resuscitation team in the delivery room. The associated anomalies often have a significant effect on the immediate as well as long-term outcome of the neonate. This report presents a case of congenital arhinia and reviews the management of such cases.

Topics: Abnormalities, Multiple; Congenital Abnormalities; Disease Management; Eye Abnormalities; Fatal Outcome; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Magnetic Resonance Imaging; Male; Nose; Rare Diseases; Respiration, Artificial; Sepsis; Tomography, X-Ray Computed; Tracheostomy; Ultrasonography, Prenatal

Alobar holoprosencephaly is a rare and severe brain malformation due to early arrest in brain cleavage and rotation.. We report a congenital anomalous fetus with alobar holoprosencephaly, prenatally diagnosed by two-dimensional (2D) sonography at the 40 weeks of gestation. The mother was affected by gestational diabetes mellitus and was obese (BMI > 30 kg/m(2)). 2D Ultrasound depicted the cerebral malformation, cyclopy, proboscis, cardiac defects (atrial septal defect, hypoplastic left heart, anomalous communication between right ventricle and aorta) and extremities defects. The newborn died just after delivery. External examination confirmed a mobile proboscis-like nose on the normal nose position. The fetus had both claw hands. The right and left feet showed to be equine. Autopsy confirmed the ultrasound diagnosis and chromosome analysis revealed trisomy 13 (47,XY,+13). Fetopathologic examination showed cyclopy, proboscis and alobar holoprosencephaly of the fetus, which was consistent with Patau syndrome.. The teratogenic effect of diabetes on fetus has been described, but no previous clinical case of a congenital anomalous fetus with trisomy 13 and maternal gestational diabetes has been reported. This case report is the first to describe 2D ultrasound diagnosis of alobar holoprosencephaly and trisomy 13 with maternal gestational diabetes mellitus.

Topics: Adult; Chromosomes, Human, Pair 13; Diabetes, Gestational; Eye Abnormalities; Female; Heart Defects, Congenital; Holoprosencephaly; Humans; Infant, Newborn; Limb Deformities, Congenital; Nose; Obesity; Pregnancy; Trisomy; Ultrasonography, Prenatal

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

Topics: Abnormalities, Multiple; Anophthalmos; Brain; DNA Mutational Analysis; Eye Abnormalities; Holoprosencephaly; Humans; Magnetic Resonance Imaging; Nose; Syndrome

Unilateral nostril agenesis together with ipsilateral alterations of the eye, ear, and face make up a spectrum of anomalies. The aim of this study is to report a case in a Japanese girl, 14 years, 5 months of age. Cephalometric analysis is provided, and orthodontic treatment is discussed.. Lateral and frontal cephalograms were compared to a Japanese control group. Outcome of the orthodontic treatment was evaluated by comparing cephalograms taken before and after orthodontic treatment.. The lateral cephalometric analysis showed a severely hypoplastic maxilla in both sagittal and vertical dimensions, coupled with a decreased posterior cranial base. The mandibular rami were asymmetric. The frontal cephalogram showed decreased cranial width and maxillary alveolar width, together with an increased interorbital distance.. Serial lateral cephalograms during the orthodontic treatment from the age of 14 to 20 years demonstrated no significant maxillary growth and some mandibular growth, coupled with labial tipping of the maxillary central incisors.

Topics: Abnormalities, Multiple; Adult; Cephalometry; Combined Modality Therapy; Ear, External; Eye Abnormalities; Facial Asymmetry; Female; Humans; Models, Dental; Nose; Orthodontics, Corrective

We report a child with right-sided heminasal aplasia in combination with anomalies of the right eye and maxilla. Unilateral aplasia of the nose is a rare congenital malformation. It is often associated with other malformations of the facial region, including abnormalities of the eye and lacrimal system, proboscis lateralis, and facial bone malformations. The eye anomalies in our patient consisted of microphthalmia with blepharophimosis and coloboma of the iris, retina and upper eyelid. Also hypoplasia of the lacrimal apparatus and right maxilla, and a rudimentary alveolar cleft on the same side were present. The embryological development of the midface can explain this association of anomalies.

Topics: Abnormalities, Multiple; Eye Abnormalities; Female; Humans; Infant, Newborn; Jaw Abnormalities; Nose

Fronto-facio-nasal dysplasia is a rare cause of facial clefts. The syndrome is characterized by paramedian facial clefts which involve the nose and palpebral fissures resulting in defects of the alae nasi and blepharophimosis, lagophthalmos, and S-shaped palpebral fissures. In addition affected children have ocular malformations such as epibulbar dermoids and colobomata of the iris or optic disk and may have a posterior encephalocele; these features distinguish this condition from fronto-nasal dysplasia and early amnion rupture sequence. We describe a child with unilateral features. Unilateral craniofacial clefts are usually assumed to have a low recurrence risk. However, fronto-facio-nasal dysplasia is an autosomal recessive condition and must be considered in any child with paramedian facial clefts.

Topics: Abnormalities, Multiple; Craniofacial Abnormalities; Encephalocele; Eye Abnormalities; Facial Asymmetry; Genes, Recessive; Humans; Infant, Newborn; Male; Nose; Syndrome

Asymmetric embryopathies--severe malformations and disruptions--that affect the craniofacial region are discussed, including anomalies of the eye, nose, mouth, and ear. Asymmetric Tessier clefts are also discussed.

Topics: Cleft Lip; Cleft Palate; Ear, External; Eye Abnormalities; Facial Asymmetry; Humans; Infant, Newborn; Mouth Abnormalities; Nose; Skull

A rare case of a newborn suffering from arhinia with complete airway obstruction is reported. The complexity of the life-threatening airway obstruction is described and adequate treatment is reported. The relevant literature is reviewed, and the different approaches to treatment are discussed.

Topics: Abnormalities, Multiple; Airway Obstruction; Eye Abnormalities; Eyelids; Female; Humans; Infant, Newborn; Nasal Cavity; Nose; Radiography

Several new "syndromes" have been described that have in common facial findings identical or similar to those seen in frontonasal malformation (FNM), previously termed frontonasal dysplasia. Some of those new syndromes are inherited, whereas FNM is an isolated finding. Thus there is a need for differentiation among those conditions. A review of the literature was undertaken to identify and classify the various reports that describe FNM as it occurs alone and in association with a syndrome.

Topics: Classification; Craniosynostoses; Eye Abnormalities; Frontal Bone; Humans; Hypertelorism; Nose; Orofaciodigital Syndromes; Skull; Syndactyly; 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

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

Oblique facial clefts are extremely rare and cause significant morbidity. Treatment of these clefts is complex and requires a fundamental understanding of cleft classification and techniques used for treatment of clefts.. We describe a novel single-staged technique to repair the Tessier no. 4 soft tissue cleft and reconstruct the buccal sulcus and bilaminar lower eyelid by preserving normally excised tissue combined with standard procedures. We also present a case report demonstrating the technique in an adolescent female. The procedure incorporates turnover flaps from soft tissue preservation within the cleft, a Mustarde cheek advancement flap, an anatomical subunit lip repair, a dorsal nasal Rieger flap for ala repositioning, and a lateral nasal flag flap.. The single-staged soft tissue repair eliminated the Tessier no. 4 cleft while simultaneously reconstructing the bilaminar lower eyelid and buccal lining. Our patient had no complications within the perioperative period.. This novel single-staged technique for the treatment of the soft tissue Tessier no. 4 cleft not only repairs the cleft but also reconstructs the buccal sulcus and bilaminar lower eyelid with turnover flaps preserved from the normally discarded excess soft tissue within the cleft. The novel repair allows for the creation of a deeper fornix to aid with placement of an orbital prosthesis and is ideal for use in underserved or remote locations.

Topics: Adolescent; Cleft Palate; Craniofacial Dysostosis; Eye Abnormalities; Eyelids; Female; Humans; Maxillofacial Abnormalities; Nose; Plastic Surgery Procedures; Surgical Flaps

Topics: Abnormalities, Multiple; Adult; Child; Cleft Lip; Cleft Palate; Ear, External; Eye Abnormalities; Genetic Association Studies; Heart Septal Defects, Atrial; Humans; Infant; Male; Maxilla; Micrognathism; Nose; Syndrome; Thumb

Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with numerous and variable clinical manifestations including conotruncal heart abnormalities, palatal anomalies, hypoparathyroidism, immune deficiency, and cognitive deficits. The clinical suspicion of this syndrome is often heightened by the presence of characteristic facial features. A previous report highlighted the under-diagnosis of this condition in African Americans, thought to be related to a paucity of typical facial features. We ascertained the largest cohort (n = 50) of African-American individuals with 22q11DS reported thus far, across five genetics centers in the United States and report on their facial and other phenotypic features. About 3/4 of our cohort has at least one dysmorphic facial feature. Auricular abnormalities, especially small ears, are the most common dysmorphic facial feature followed by nasal and ocular abnormalities. Skeletal findings are seen in about 2/3 of our cohort, higher than the typical frequency reported in 22q11DS. Cardiac anomalies, developmental delay, and palatal abnormalities are seen at a lower frequency in our cohort. Thus, it is evident that the features traditionally associated with 22q11DS are difficult to recognize in African-American individuals with this syndrome, due to both altered frequencies of major anomalies and a non-classic facial appearance. Therefore, a high index of suspicion is needed to recognize 22q11DS in African-American individuals.

Topics: Abnormalities, Multiple; Adolescent; Adult; Aged; Black or African American; Child; Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 22; Cognition Disorders; Cohort Studies; Ear; Eye Abnormalities; Facies; Female; Heart Defects, Congenital; Humans; Hypoparathyroidism; Immune System Diseases; Infant; Male; Middle Aged; Nose; Phenotype; Retrospective Studies

Amniotic band syndrome is an uncommon congenital pathological condition that may lead to malformations and foetal-infant death. We report an autoptic case. The patient was a male preterm infant. At 14 weeks of gestation, a routine ultrasonography showed severe craniofacial anomalies and a close contiguity of the foetal head with the amnios. The neonate survived three days, after which an autopsy was carried out. The infant had a frontoparietal meningoencephalocele; a fibrous band was attached to the skin, close to the meningoencephalocele base. Cleft lip and palate, nose deformation and agenesis of the right eye were also present. At the opening of the cranial cavity, occipital hyperostosis was observed. The herniated brain showed anatomical abnormalities that made identification of normal structures difficult. Microscopically, the nervous parenchyma had architectural disorganization and immaturity, and the fibrous band consisted of amniotic membranes. As evident from this case report, amniotic band syndrome may cause severe malformations and foetal-infant death.

Topics: Amniotic Band Syndrome; Autopsy; Cleft Palate; Encephalocele; Eye Abnormalities; Humans; Infant, Newborn; Male; Nose

Topics: Brain; Craniofacial Abnormalities; Eye Abnormalities; Fatal Outcome; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; India; Infant, Newborn; Magnetic Resonance Imaging; Male; Mouth Abnormalities; Nose; Tomography, Spiral Computed; Twins, Conjoined

Topics: Adult; Eye Abnormalities; Female; Fetal Death; Fetal Diseases; Humans; Infant, Newborn; Nose; Pregnancy; Pregnancy in Diabetics

Topics: Child, Preschool; Chromosomes, Human, Pair 9; Comparative Genomic Hybridization; Craniofacial Abnormalities; Eye Abnormalities; Frontal Bone; Humans; Male; Monosomy; Nose; Radiography

47 XYY syndrome is a sporadic condition in which the human male receives an extra Y chromosome. Few ocular associations have been documented. The authors report the first case of 47 XYY associated with morning glory syndrome, frontonasal meningoencephalocele, and midfacial defects.

Topics: Abnormalities, Multiple; Acrocallosal Syndrome; Child; Encephalocele; Eye Abnormalities; Frontal Lobe; Humans; Hypertelorism; Karyotyping; Magnetic Resonance Imaging; Male; Meningocele; Nose; Optic Disk; Syndrome; XYY Karyotype

Oculoauriculofrontonasal syndrome was the subset of patients with oculo-auriculo-vertebral spectrum and frontonasal malformation. Radiographic evidence of tracheal duplication was documented in a male infant with oculoauriculofrontonasal syndrome. Although previously unreported in oculoauriculofrontonasal syndrome, airway anomalies in our case can be attributed to the oculo-auriculo-vertebral component of the oculoauriculofrontonasal syndrome.

Topics: Abnormalities, Multiple; Eye Abnormalities; Female; Humans; Infant, Newborn; Male; Nose; Respiratory System Abnormalities; Spine; 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

Craniofrontonasal dysplasia is a rare, familial X-linked syndrome with coronal synostosis (brachycephaly or plagiocephaly), hypertelorbitism (frequently asymmetric), and extracranial anomalies. Details of the timing and technique of the craniofacial correction have not been well described. The largest series of patients with craniofrontonasal dysplasia treated at a single institution was used for review.. A review of patients at the University of California, Los Angeles Craniofacial Clinic with the diagnosis of craniofrontonasal dysplasia was performed (n = 21). Data included office, hospital, and operative records; photographs; lateral cephalograms; and three-dimensional computed tomographic scans. Based on surgical outcomes, a treatment algorithm was created.. Fourteen patients were female, seven were male, and five had a family history of craniofrontonasal dysplasia (24 percent). Eight patients had unilateral coronal synostosis (plagiocephaly) and 13 had bilateral coronal synostosis (brachycephaly). Eleven patients had asymmetric hypertelorbitism and 10 had symmetric hypertelorbitism. Patients also had cleft lip-cleft palate (10 percent), ear deformities (19 percent), strabismus or esotropia (81 percent), dry frizzy hair (100 percent), syndactyly (14 percent), and nail (100 percent) or other anomalies. After fronto-orbital advancement, no patients had increased intracranial pressure problems or difficulty related to resynostosis. After hypertelorbitism correction, three patients relapsed. Because of this, correction in later patients was delayed until after eruption of permanent maxillary incisors. The mean anterior interorbital distance was reduced in patients from 184 percent to 98 percent of sex-matched controls.. The phenotypic expression of craniofrontonasal dysplasia is described to recognize patients early. A treatment algorithm for craniofrontonasal dysplasia based on timing and technique is offered to decrease the need for revision and improve outcomes.

Topics: Abnormalities, Multiple; Algorithms; Cleft Lip; Cleft Palate; Craniosynostoses; Eye Abnormalities; Female; Genetic Diseases, X-Linked; Hair; Humans; Hypertelorism; Infant; Limb Deformities, Congenital; Male; Nails, Malformed; Nose; Plastic Surgery Procedures; Retrospective Studies; Treatment Outcome

A German Fleckvieh calf was diagnosed with cyclopia in shape of united eye sockets in one orbit. However, two fully developed eye balls were present while the nostril was not developed. The malformed calf was inbred on a bull used for artificial insemination (AI) with an inbreeding coefficient of 3.125%. Teratogenic plant alkaloids were unlikely to be responsible for the malformation of this calf. Neither in the five progeny of the dam nor in the descendants of the AI-bull with a total of 8083 calvings, calves with such anomalies were found.

Topics: Animals; Animals, Newborn; Cattle; Craniofacial Abnormalities; Eye Abnormalities; Fatal Outcome; Female; Inbreeding; Nose; Orbit

Topics: Abnormalities, Multiple; Arachnoid Cysts; Eye Abnormalities; Humans; Infant; Nose; Tomography, X-Ray Computed

Topics: Abortion, Eugenic; Eye Abnormalities; Female; Holoprosencephaly; Humans; Imaging, Three-Dimensional; Nose; Pregnancy; Pregnancy Outcome; Ultrasonography, Prenatal

We report a patient with bilateral microphthalmia with cyst, limb anomalies, and multiple facial malformations. This patient has clinical features similar to Waardenburg ophthalmo-acromelic syndrome, cerebro-oculo-nasal syndrome, and craniotelencephalic dysplasia. Although all of these syndromes are characterized by microphthalmia, the presently reported patient does not have the complete pattern of any of these syndromes, It is possible that he has a previously undescribed syndrome, most closely related to the cerebro-oculo-nasal syndrome with malformations outside the craniofacial region. More case reports are needed to further delineate this possibly new syndrome.

Topics: Abnormalities, Multiple; Brain; Child, Preschool; Craniofacial Dysostosis; Cysts; Eye Abnormalities; Humans; Limb Deformities, Congenital; Male; Microphthalmos; Nose; Syndrome; Telencephalon; Waardenburg Syndrome

We present a male infant 2.5-months old with asymmetric skull, anophthalmia, apparent hypertelorism, abnormal nares, unilateral cleft lip and palate, and structural abnormalities of the central nervous system. These findings are similar to cerebro-oculo-nasal syndrome except for the appearance of nose. This case is either a clinical variability in cerebro-oculo-nasal syndrome or a new entity.

Topics: Abnormalities, Multiple; Anophthalmos; Brain; Cleft Lip; Cleft Palate; Eye Abnormalities; Humans; Hypertelorism; Infant; Male; Nose; Syndrome; Tomography, X-Ray Computed

Because many patients with velocardiofacial syndrome (VCFS) are first examined by otolaryngologists for ear or speech problems before being diagnosed with VCFS, we describe a series of patients with this genetic disorder, which is associated with multiple anomalies, including velopharyngeal insufficiency, cardiac defects, characteristic facial features, and learning disabilities.. We retrospectively analyzed the medical charts and available nasoendoscopic observations for 35 patients who were diagnosed with VCFS and who had a microscopic deletion in chromosome 22q11 as shown by DNA probe and fluorescence in situ hybridization.. For most patients, the medical chart documented cardiac anomalies, velopharyngeal insufficiency with hypernasal speech, and characteristic facial features including nasal, auricular, craniofacial, and ocular abnormalities. Incidence of middle ear infection with associated conductive hearing loss was also high and necessitated early placement of pressure equalization tubes. Some patients were treated with adenoidectomy for chronic otitis media; consequently, velopharyngeal insufficiency and hypernasal speech worsened. Nasoendoscopic examination as documented in the medical chart showed occult cleft palate, a small adenoid pad, and pulsation in the muscular wall.. Otolaryngologists have an important role in diagnosis and treatment of persons with VCFS and therefore should familiarize themselves with the typical history and most frequent head and neck manifestations of this syndrome.

Topics: Adolescent; Adult; Child; Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 22; Cleft Palate; Craniofacial Abnormalities; DNA Probes; Ear, External; Endoscopy; Eye Abnormalities; Female; Hearing Loss, Conductive; Heart Defects, Congenital; Humans; In Situ Hybridization, Fluorescence; Infant; Learning Disabilities; Male; Nose; Otitis Media; Otorhinolaryngologic Diseases; Retrospective Studies; Speech Disorders; Syndrome; Velopharyngeal Insufficiency

Cerebro-oculo-nasal syndrome is a rare multiple congenital anomaly syndrome with structural anomalies of the central nervous system, anophthalmia, and abnormal nares. In this report two additional cases are presented, one of them without central nervous system and/or ocular anomalies.

Topics: Abnormalities, Multiple; Brain; Eye Abnormalities; Female; Humans; Infant, Newborn; Male; Nose; Syndrome; Tomography, X-Ray Computed

Oculodentodigital dysplasia (ODDD) is an autosomal dominant condition with high penetrance and variable expressivity. The anomalies of the craniofacial region, eyes, teeth, and limbs indicate abnormal morphogenesis during early fetal development. Neurologic abnormalities occur later in life and appear to be secondary to white matter degeneration and basal ganglia changes. In familial cases, the dysmorphic and/or neurodegenerative components of the phenotype can be more severe and/or present at a younger age in subsequent generations, suggesting genetic anticipation. These clinical features suggest that the ODDD gene is pleiotropic with important functions throughout pre- and postnatal development. We have performed two-point linkage analysis with seven ODDD families and 19 microsatellite markers on chromosome 6q spanning a genetic distance of approximately 11 cM in males and 20 cM in females. We have refined the location of the ODDD gene between DNA markers D6S266/D6S261 (centromeric) and D6S1639 (telomeric), an interval of 1.01 (male) to 2.87 (female) cM. The strongest linkage was to DNA marker D6S433 (Zmax = 8.96, thetamax = 0.001). Families show significant linkage to chromosome 6q22-q23 and no evidence for genetic heterogeneity.

Topics: Abnormalities, Multiple; Chromosome Mapping; Chromosomes, Human, Pair 6; DNA; Eye Abnormalities; Family Health; Female; Genetic Linkage; Genetic Markers; Haplotypes; Humans; Lod Score; Male; Nose; Odontodysplasia; Pedigree; Syndactyly; Tongue

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

We report on two families with the oculodentodigital (ODD) dysplasia syndrome, also called Meyer-Schwickerath syndrome. It represents a rare disorder characterized by eye and facial abnormalities causing a unique facial appearance. The phenotype of the young patients resembles those of identical twins. We found syndactyly mostly at the hands and, additionally, characteristic phalangeal aberrations, defects in teeth enamel, and trichosis. In the one family, the ODD dysplasia syndrome seemingly originated in a new mutation. The affected child was treated surgically in our clinic (syndactyly separation). In the other family, three patients (grandmother, mother, and granddaughter) were subjects of syndactyly separation. The aim of our surgeries was to separate the webbed fingers so there would be a normal spread and to improve the function and appearance of fingers. The ODD dysplasia syndrome correlates with the Hallermann-Streiff syndrome, or oculomandibulodyscephaly, which is characterized by a typical skull shape (brachicephaly with frontal brossing), a bird-like face, and eye abnormalities (congenital cataracts and microphthalmia).

Topics: Abnormalities, Multiple; Adult; Child, Preschool; Eye Abnormalities; Female; Humans; Nose; Syndactyly; Tooth Abnormalities

Mice with homozygous mutations of the Pax-6 gene exhibit a constellation of developmental problems including the absence of eyes and nasal cavities and problems in the movement of neuroblasts out of the germinal epithelium. In this paper, we demonstrate further disturbances in neuronal migration. Normally, cells produced along the lateral ventricles move laterally across the pallium, ultimately coming to reside in the lateral neocortex and primary olfactory cortex. In mutant animals, these cells continue to migrate to the pial surface of the brain.

Topics: Animals; Cell Movement; Cerebral Cortex; Cerebral Ventricles; DNA-Binding Proteins; Eye Abnormalities; Eye Proteins; Homeodomain Proteins; Homozygote; Mice; Mice, Neurologic Mutants; Mutation; Neurons; Nose; Paired Box Transcription Factors; PAX6 Transcription Factor; Prosencephalon; Repressor Proteins

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

Oculodentodigital syndrome (O.D.) is an autosomal dominant disorder comprising facial anomalies, syndactyly, microcorneae, dental enamel hypoplasia, and leukodystrophy. We describe a four generation family with O.D. in which anomalies such as syndactyly appear congenitally, whereas neurological (i.e., leukodystrophic) signs and symptoms tend to be expressed in a more severe form and/or at an earlier age of onset in successive generations of the kindred. This pattern of phenotypic expression is consistent with the phenomenon of genetic anticipation, and we suggest that O.D. may be a trinucleotide repeat disorder.

Topics: Abnormalities, Multiple; Adult; Age of Onset; Eye Abnormalities; Face; Female; Humans; Male; Nervous System Diseases; Nose; Pedigree; Syndactyly; Syndrome; Tooth Abnormalities; Trinucleotide Repeats

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

Holoprosencephaly is a congenital defect of the median structures of the brain and face. The epidemiology is poorly known due to the paucity of population-based studies. This study describes the epidemiology of holoprosencephaly in a large population, using cases identified through the New York State Congenital Malformations Registry, and born in 1984-1989. We describe the craniofacial abnormalities present, their frequency, and their cooccurrence, and we examine the correspondence between the severity of craniofacial abnormalities, chromosomal abnormalities, and severity of the brain defect. Liveborn cases totaled 78, yielding a prevalence of 4.8 per 100,000 live births. Prevalence among girls was nearly double that in boys, and was 4.2 times higher among infants of mothers under age 18 compared to infants of older mothers. Only 9.8% of all cases had no craniofacial abnormalities other than the brain defect. Eye malformations were present in 76.8%, nose malformations in 69.5%, ear malformations in 50%, and oral clefts in 41.5%. These malformations arise at different times during gestation. The variability in patterns of cooccurrence suggests variability in the developmental pathways and/or timing of developmental derangements which result in holoprosencephaly. This, in turn, is consistent with a model of multiple causes. Children with alobar holoprosencephaly tended to have the most severe craniofacial anomalies, but the correspondence was not 100%. Craniofacial phenotype does not consistently discriminate between cytogenetically normal and abnormal cases.

Topics: Chromosome Aberrations; Chromosome Disorders; Craniofacial Abnormalities; Eye Abnormalities; Female; Genetic Variation; Holoprosencephaly; Humans; Infant; Infant, Newborn; Male; New York; Nose; Phenotype; Prevalence

The anterior part of the vertebrate head expresses a group of homeo box genes in segmentally restricted patterns during embryogenesis. Among these, Otx2 expression covers the entire fore- and midbrains and takes place earliest. To examine its role in development of the rostral head, a mutation was introduced into this locus. The homozygous mutants did not develop structures anterior to rhombomere 3, indicating an essential role of Otx2 in the formation of the rostral head. In contrast, heterozygous mutants displayed craniofacial malformations designated as otocephaly; affected structures appeared to correspond to the most posterior and most anterior domains of Otx expression where Otx1 is not expressed. The homo- and heterozygous mutant phenotypes suggest Otx2 functions as a gap-like gene in the rostral head where Hox code is not present. The evolutionary significance of Otx2 mutant phenotypes was discussed for the innovation of the neurocranium and the jaw.

Topics: Abnormalities, Multiple; Animals; Base Sequence; Ear; Embryo, Mammalian; Epithelium; Eye Abnormalities; Gene Expression Regulation, Developmental; Gestational Age; Haploidy; Head; Heterozygote; Homeodomain Proteins; Homozygote; Jaw Abnormalities; Mice; Mice, Transgenic; Molecular Sequence Data; Mutation; Nerve Tissue Proteins; Nervous System Malformations; Nose; Otx Transcription Factors; Phenotype; Trans-Activators

Fraser syndrome is a rare autosomal recessive disorder whose major manifestations are cryptophthalmos, syndactyly and genital abnormalities. These patients also frequently have malformations of the ears, nose and/or larynx. The diagnosis is usually made at birth from the obvious malformations, although occasionally made on prenatal ultrasound. Treatment is dependent on which malformations are present and genetic counseling is indicated. Prognosis is dependent on the severity of renal and laryngeal malformations.

Topics: Coloboma; Ear; Eye Abnormalities; Female; Genitalia; Humans; Infant, Newborn; Larynx; Nose; Prognosis; Severity of Illness Index; Syndactyly; Syndrome

Nasal gliomas are rare, benign, congenital masses more accurately referred to a sequestered glial tissue. Seven patients with nasal glioma treated by Hugh G. Thomson over the last 28 years are presented with special reference to tumor recurrence after excision and associated naso-ocular cleft. Three of our patients had an associated ipsilateral naso-ocular cleft, and three similar cases have been reported. This association is probably more frequent because a naso-ocular cleft can exist as a forme fruste and be easily overlooked. The first two tumors resected in our series recurred within 10 months; however, no recurrences were seen after a new treatment protocol was initiated in 1972. This consisted of total excision of the skin overlying the tumor if the skin adhered to the mass or if glial elements were seen within the dermis on frozen section. Deep resection margin was also assessed by frozen section of the nasal mucosa or fibrous stalk of the tumor. Accordingly, unnecessary intracranial procedures were avoided without increasing the risk of recurrence.

Topics: Abnormalities, Multiple; Child; Choristoma; Dermatologic Surgical Procedures; Eye Abnormalities; Female; Humans; Infant; Male; Neoplasm Recurrence, Local; Nose; Nose Diseases

We describe a father and his child with bilateral syndactyly of fingers IV and V and with pinched nose, hypoplastic alae nasi and thin anteverted nares. The patients also showed a small nodule on the tongue tip. Both had no ocular or dental anomalies. The clinical features of our patients resemble those of the patients described by Brueton et al. The hypothesis that the oculodentodigital dysplasia may belong to a contiguous gene spectrum could be confirmed.

Topics: Abnormalities, Multiple; Adult; Eye Abnormalities; Humans; Infant; Male; Nose; Odontodysplasia; Syndactyly; Tongue

The ophthalmologic findings associated with frontonasal dysplasia have not been defined previously in a large series of untreated children. We reviewed the ophthalmic manifestations of a series of patients with frontonasal dysplasia who were seen as part of their craniofacial evaluation. All had undergone a complete ophthalmologic examination before any manipulation of either the orbits or the soft tissues of the orbital contents. From 1986 to 1991, 23 patients with frontonasal dysplasia were seen; ophthalmologic abnormalities were found in 20 (87 percent). Abnormalities included significant refractive errors, strabismus, nystagmus, and eyelid ptosis. Three patients had amblyopia, a treatable cause of visual loss, from strabismus or anisometropia. Ten eyes in seven patients (30 percent) had severe structural anomalies, such as optic nerve hypoplasia, optic nerve colobomas, microphthalmia, cataract, corneal dermoid, or inflammatory retinopathy, that resulted in an acuity of 20/100 or worse. The high incidence of ocular abnormalities indicates that early assessment by an ophthalmologist should be part of the initial evaluation of patients with frontonasal dysplasia to detect treatable visual or ocular problems.

Topics: Abnormalities, Multiple; Child; Child, Preschool; Eye Abnormalities; Eye Diseases; Facial Bones; Female; Humans; Infant; Infant, Newborn; Male; Nose; Retrospective Studies; Skull

The rat small eye strain (rSey) lacks eyes and nose in the homozygote, and is similar to the mouse Sey strain with mutations in the Pax-6 gene. We isolated Pax-6 cDNA clones from an rSey homozygote library, and found an internal deletion of about 600 basepairs in the serine/threonine-rich domain. At the genomic level, a single base (G) insertion in an exon generates an abnormal 5' donor splice site, thereby producing the truncated mRNA. Anterior midbrain crest cells in the homozygous rSey embryos reached the eye rudiments but did not migrate any further to the nasal rudiments, suggesting that the Pax-6 gene is involved in conducting migration of neural crest cells from the anterior midbrain.

Topics: Alternative Splicing; Amino Acid Sequence; Animals; Base Sequence; DNA Primers; DNA-Binding Proteins; Embryo, Mammalian; Exons; Eye Abnormalities; Eye Proteins; Homeodomain Proteins; Homozygote; Microscopy, Electron, Scanning; Molecular Sequence Data; Nose; Paired Box Transcription Factors; PAX6 Transcription Factor; Polymerase Chain Reaction; Rats; Rats, Mutant Strains; Rats, Sprague-Dawley; Repressor Proteins; Restriction Mapping; Sequence Deletion; Transcription Factors

The chronologic changes in eyeball position in relation to bony landmarks were studied by CT scans. The results were applied to the preoperative evaluation in 16 craniofacial synostosis patients. Ten subjects from each age group were selected from more than 2000 subjects who underwent CT scanning of the skull without any brain and skull diseases. These age groups ranged from birth to 20 years of age. The following four distances were measured on the CT section incorporating lenses: (1) the distance from the dorsum sellae to the lenses, (2) the distance between the lateral orbital rim and the lenses, (3) the distance from the nasal root to the lenses, and (4) the width between the lenses. These distances also were measured in 16 craniofacial synostosis patients preoperatively, and the results were compared with those of the healthy individuals in the same age group. The distances of the lenses from the nasal root and from the lateral orbital rim were larger than in the healthy individuals in almost all craniofacial synostosis patients. However, the distance from the dorsum sellae to lenses was the same as that in healthy individuals on the whole.

Topics: Adolescent; Adult; Aging; Cephalometry; Child; Child, Preschool; Exophthalmos; Eye; Eye Abnormalities; Facial Bones; Humans; Infant; Lens, Crystalline; Nose; Orbit; Reference Values

Phenotypic parallels and genetic evidence from comparative mapping suggest that the murine Small eye (Sey) and human aniridia (AN) disorders are homologous. This report describes the isolation of a murine embryonic cDNA that is structurally homologous to the AN cDNA were recently cloned. The murine cDNA detects a 2.7-kb transcript in the adult mouse eye and cerebellum and in human glioblastomas, suggesting a neuroectodermal involvement in the etiology of Sey/AN. Sequence comparison between the murine and the human cDNAs revealed extensive homology in nucleotide sequence (greater than 92%) and virtual identity at the amino acid level. None of the differing amino acids was located within the paired box and homeobox DNA-binding domains. These results provide evidence for a common molecular basis underlying the two genetic disorders and suggest that the Sey system would be an authentic model for human AN.

Topics: Amino Acid Sequence; Animals; Aniridia; Base Sequence; Brain; Central Nervous System Neoplasms; Cloning, Molecular; DNA; Eye; Eye Abnormalities; Gene Expression; Gene Expression Regulation, Neoplastic; Genes, Lethal; Humans; Mice; Molecular Sequence Data; Neural Crest; Nose; Organ Specificity; Regulatory Sequences, Nucleic Acid; RNA, Messenger; RNA, Neoplasm; Sequence Homology, Nucleic Acid; Tumor Cells, Cultured

The clinical and radiographic changes in a case of oculodentodigital syndrome are presented. The characteristic features of this rare developmental disorder, microphthalmus with microcornea and iris anomalies, hypertelorism, thin nose with hypoplastic alae and anteverted nostrils, syndactyly with camptodactyly and clinodactyly of the fourth and fifth fingers associated with bony anomalies of the middle phalanges of the fifth fingers and toes, were all present. In addition, histological examination of a lateral incisor showed the enamel dysplasia to be due to enamel hypoplasia; the dentine also showed marked hypocalcification. There were widespread pulp denticles and hypercementosis throughout the dentition. Both the patient and his mother had coronoid hypoplasia.

Topics: Adult; Dental Enamel Hypoplasia; Eye Abnormalities; Fingers; Humans; Hypercementosis; Jaw Abnormalities; Male; Nose; Syndrome; Toes; Tooth Calcification

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

We describe a case of complete nasal agenesis and absence of the nasal fossae, without alterations in the central nervous system. The physical and intellectual development of the infant to date has been absolutely normal. Opening of the nasal respiratory passage was not required in our patient as he did not show respiratory problems during deglutition. - Microphthalmia in the right eye with iridoretinal coloboma and right cryptorchidism were also noted. When the child was 9 months old a right orbital asymmetry became evident due to a growth deficit of the microphthalmic eye. This improved after placement of an expandable prosthesis in the orbit to stimulate its growth. - When the child is 4 years old, he will start to use a nasal prosthesis supported by implantology. Final reconstruction of the nasal pyramid will take place after he is 15 years of age.

Topics: Child, Preschool; Eye Abnormalities; Humans; Infant; Infant, Newborn; Male; Nasal Bone; Nasal Cavity; Nasal Septum; Nose; Orbit; Tomography, X-Ray Computed

Cebocephaly (hypotelorism, single-nostril nose) and ethmocephaly (hypotelorism, interorbital proboscis) lie in the middle of the spectrum of craniofacial changes associated with holoprosencephaly. Because these defects and thorough anatomic studies of them are rare, knowledge concerning morphologic as well as pathogenetic relationships is lacking. We report the autopsy findings and anatomic features of the dried skull of a 31 week fetus with cebocephaly and the craniofacial dissection of a 36 week fetus with ethmocephaly. Both manifested dysplastic changes of the ethmoid bone and anterior portion of the sphenoid bone, with concomitant hypotelorism and defects of the medial orbital walls. Through these latter defects, the eyes were joined in the ethmocephalic fetus (synophthalmia). Other changes of bone (single optic foramen, approximated maxillae, choanal atresia, thickened palate) and soft tissue (eccentric or fused extraocular muscles, single optic nerve) in both fetuses resembled those reported in other cases of cebocephaly and ethmocephaly, as well as cyclopia. In the 19th century, both cebocephaly and ethmocephaly were classified as two-orbit variants of cyclopia, a view supported by the present study.

Topics: Ethmoid Bone; Eye Abnormalities; Facial Bones; Female; Holoprosencephaly; Humans; Infant, Newborn; Nose; Skull; Sphenoid Bone

Findings of 55 ultrasound examinations have been evaluated in 35 fetuses with various facial malformations detected by ultrasound and confirmed at birth. Ultrasonographic presentations and diagnostic criteria are given for major facial, palate and lip clefts, abnormal nasal shape, hypo and hypertelorism, microphthalmia, exophthalmia, micro and macrogenia, macroglossia. Ultrasonography proves to be a highly revealing diagnostic study with the provision of a good structural visualization and physicians' skill.

Topics: Cleft Palate; Eye Abnormalities; Female; Humans; Hypertelorism; Nose; Pregnancy; Ultrasonography, Prenatal

We report on a newborn male with deletion of part of 11q, the 27th reported case. Our patient had some of the clinical characteristics of the 11q- syndrome, but his male gender, liveborn status, q21 breakpoint, and mosaicism were unusual. In addition, he demonstrated holoprosencephaly, with cyclopia and arhinencephaly, manifestations previously unreported in the 11q- syndrome. We discuss the above points and review the literature on 11q-.

Topics: Abnormalities, Multiple; Brain; Chromosome Deletion; Chromosomes, Human, Pair 11; Ear, External; Eye Abnormalities; Humans; Hydrocephalus; Hypospadias; Infant, Newborn; Male; Mosaicism; Nose; Syndrome

The classification by Tessier of rare craniofacial clefts brought, for the surgeon, order to a previously confusing array of anatomic and developmental descriptions. An ordered two-dimensional categorization of severe clefting malformations evolved from his clinical, radiologic, and surgical observations. The purpose of this paper is to report a complete series of facial clefts studied with computed tomography (CT) and three-dimensional reconstruction. The CT analysis supports some, but contradicts other, hypotheses and speculations presented by Tessier. The CT data reveal the scale of the reconstructive challenge and allow the assessment of our therapeutic interventions.

Topics: Adolescent; Adult; Child; Child, Preschool; Cleft Lip; Cleft Palate; Eye Abnormalities; Facial Bones; Female; Humans; Infant; Male; Mandibulofacial Dysostosis; Maxilla; Nose; Orbit; Tomography, X-Ray Computed; Zygoma

A lateral proboscis usually occurs in the region of the inner canthus. We present a case of holoprosencephaly accompanied by an oblique facial cleft and an anterior encephalocele in which a proboscis lateralis occurred in a very lateral location.

Topics: Abnormalities, Multiple; Brain; Cerebellar Diseases; Child, Preschool; Cleft Lip; Cleft Palate; Encephalocele; Eye Abnormalities; Facial Bones; Female; Humans; Hypertelorism; Nose

In a study of swine congenital anomalies, nine newborn piglets with varying degrees of optic hypotelorism including cyclopia were collected. Nasal and maxillary development were abnormal in all animals regardless of the degree of eye fusion. All animals except one had intact upper lips and hard palates that carried two or three small extopic teeth. The "snout" was only a medial wedge-shaped rudiment projecting from the upper lip. It was distally covered by a typical snout-like glabrous epithelium and carried small vibrissae. Six animals also had a tubular proboscis dorsal to the eye. The distal tip of the proboscis was covered by glabrous epithelium. External nares and nasal passageways, albeit blind-ended, were prominent in the proboscis. The nasofrontal bones projected into the base of the proboscis. Seven piglets were hairless except for fine vibrissae and some eyebrow hairs. All animals had some degree of ear abnormalities, e.g., malposition and absence of external auditory meatus. In all animals the brain was malformed. This abnormality varied from complete absence of the forebrain to an alobar structure with gyri. The remainder of the body of each animal was normal. Developmental anomalies of the nose and eye generally reflect malformations of the forebrain, although the etiology of these defects is unclear. The cyclopia associated with the medial proboscis suggests that both the telencephalon and diencephalon are dysplastic. The presence of glabrous epithelium in two regions on the face suggests that studies of the development of the midline face in the swine will help to elucidate the etiology of the holoprosencephalic series. In this way the pig may prove to be an excellent modeling system for human holoprosencephaly.

Topics: Abnormalities, Multiple; Animals; Brain; Disease Models, Animal; Eye Abnormalities; Face; Female; Male; Maxilla; Medial Forebrain Bundle; Nose; Radiography; Swine

Topics: Adult; Eye Abnormalities; Face; Female; Fetal Diseases; Humans; Microcephaly; Nose; Pregnancy; Prenatal Diagnosis; Ultrasonography

A macroscopic study on the missing elements in cyclopia (a single eye or closely approximated eyes with all intergrades in a single orbit) with or without proboscis and hypotelorism was performed on 12 human fetuses and 2 human fetal skulls. In addition, microscopic investigations were carried out on the orbital contents of the cyclops with a single eye without proboscis, crown-heel length (C-HL) 37 cm, and on the 6.5-mm-crown-rump length (C-RL) human embryo with a single nasal placode localized in front of two eye cups. In the embryo and in all 14 fetal cases the midfacial region was more-or-less deficient. In the two cyclopia cases without proboscis the nasal placode(s) had not developed at all during the embryonic period. In cases with proboscis, consisting of a single tube localized above both eyes, and in the hypotelorismic specimens, there could only have been a single nasal placode during development: a situation evident in the 6.5-mm-C-RL human embryo. In this holoprosencephalic embryo the single nasal placode was undulated, as if formed from two fused nasal placodes, and flanked by the prospective areas for the lateral nasal processes. Caudally, it was bordered by the maxillary processes. In view of the position of the single placode in this embryonic face, as described above, it is most likely that this is a preliminary stage of hypotelorism. Moreover, both medial nasal processes with the internasal groove in between, i.e., the interplacodal area, were missing.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abnormalities, Multiple; Eye Abnormalities; Facial Bones; Humans; Nose; Orbit; Skull

The typical ultrasound findings in cases of fetal holoprosencephaly with hypotelorism and cyclopia are explained with reference to a case history. Hypotelorism was confirmed by measurement of the distance between the orbits of the fetus.

Topics: Abnormalities, Multiple; Adult; Brain; Eye Abnormalities; Facial Bones; Female; Fetal Growth Retardation; Humans; Infant, Newborn; Male; Nose; Pregnancy; Prenatal Diagnosis; Ultrasonography

Topics: Abnormalities, Multiple; Adult; Diseases in Twins; Ear; Eye Abnormalities; Female; Genes, Recessive; Humans; Infant, Newborn; Kidney; Nose; Pregnancy; Syndrome; Terminology as Topic; Twins, Monozygotic

We report on a newborn infant with mosaic trisomy 9. The patient shared only a few anomalies with the previously reported cases of this chromosome abnormality but had a severe craniofacial malformation not yet reported in this syndrome.

Topics: Abnormalities, Multiple; Chromosomes, Human, 6-12 and X; Eye Abnormalities; Facial Bones; Female; Humans; Infant, Newborn; Mosaicism; Nose; Phenotype; Skull; Trisomy

Three new cases of oculodentodigital (ODD) syndrome are reported. The clinical features are discussed and the development of the characteristic facial appearance is illustrated. Conductive deafness is reported in one of our cases and has been reported in six previous cases. It is suggested that it is a feature of the syndrome which is amenable to treatment.

Topics: Abnormalities, Multiple; Dental Enamel Hypoplasia; Eye Abnormalities; Female; Fingers; Humans; Male; Nose; Syndrome

We report on a 2-month-old girl whose parents are first cousins. The patient has severe craniofacial anomalies characterized by: encephalocele, hypertelorism, midface hypoplasia, hypoplasia of frontal bone on the left side, malformed left eye, absent inner eyelashes, irregular S-shaped palpebral fissures, deformed nostrils, hypoplastic right nasal wing and cleft lip, and clefts of premaxilla, palate and uvula. No other malformations were observed. This association of anomalies suggests the diagnosis of frontofacionasal dysplasia. Parental consanguinity suggests autosomal recessive inheritance.

Topics: Abnormalities, Multiple; Consanguinity; Craniofacial Dysostosis; Encephalocele; Eye Abnormalities; Female; Genes, Recessive; Humans; Infant; Nose

The importance of skeletal reduction of the interorbital distance in the treatment of patients with teleorbitism is now well recognized. In spite of this, results of surgery are not always as good as one would hope. For this there are two reasons: (1) reduction of the interorbital distance may be followed by deformities such as canthal drift, enophthalmus, pseudoptosis, and so forth; and (2) hypertelorism is frequently associated with a variety of other malformations that become more conspicuous after reduction of the interorbital distance. In this paper attention is focused on the mechanisms responsible for the appearance of new stigmata, on their prevention, and also on the treatment of the associated malformations.

Topics: Abnormalities, Multiple; Adult; Blepharoptosis; Child; Child, Preschool; Craniofacial Dysostosis; Eye Abnormalities; Facial Asymmetry; Female; Humans; Hypertelorism; Lacrimal Apparatus; Male; Nose; Oculomotor Muscles; Orbit; Rhinoplasty; Surgery, Plastic

Temporal bone findings in a fetus with trisomy 13 syndrome and cyclopia may be histopathologically characterized by the dysplasia of bony and membranous labyrinth and of the nervous system. In the left ear, there was a shortened cochlea housing a malformed Corti's organ appearing as a ribbonlike structure, an unexpected canal running obliquely through the scala tympani, a peculiar shape of the utricular macula and posterior canal crista, and a delayed ossifying process in the otic capsule. The poor development of the structures in the seventh and eighth nerves and their ganglions was observed in both ears. The type of anomaly can be classified as Mondini or Mondini-Alexander. The several anomalies might involve the organs that begin to develop during the period from five to eight gestational weeks.

Topics: Abnormalities, Severe Teratoid; Adult; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, 13-15; Ear; Eye Abnormalities; Face; Female; Humans; Nose; Pregnancy; Temporal Bone; Trisomy

Congenital ocular and related anomalies were studied in two unrelated young raccoons. One animal was anophthalmic and had severe anomalies of the central nervous system, consisting of meningoencephalocele, pachygyria, hydranencephaly, cerebellar cavitation, syringomyelia, and other defects. A second animal was microphthalmic with congenital defects of the nose, maxilla and teeth. Ocular lesions were severe and included chorioretinal coloboma, retinal folds, disorganized neuroectodermal cell layers, spherophakia, cataract and other defects. The nose had unilateral abnormal epithelium, hair follicles, sweat glands and sebaceous glands, and a lack of parietal cartilage on the affected side.

Topics: Abnormalities, Multiple; Animals; Central Nervous System; Eye; Eye Abnormalities; Female; Male; Maxilla; Nose; Raccoons; Spinal Cord

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

The craniofacial anatomy of an infant with facial duplication is described. There were four eyes, two noses, two maxillae, and one mandible. Anterior to the single pituitary the brain was duplicated and there was bilateral arhinencephaly. Portions of the brain were extruded into a large frontal encephalocele. Cases of symmetrical facial duplication reported in the literature range from two complete faces on a single head (diprosopus) to simple nasal duplication. The variety of patterns of duplication suggests that the doubling of facial components arises in several different ways: Forking of the notochord, duplication of the prosencephalon, duplication of the olfactory placodes, and duplication of maxillary and/or mandibular growth centers around the margins of the stomatodeal plate. Among reported cases, the female:male ratio is 2:1.

Topics: Eye Abnormalities; Face; Female; Humans; Infant, Newborn; Mandible; Maxilla; Nose

The craniofacial complex of two neonatal, human, cyclopic specimens was studied in detail. Both specimens exhibited a single ocular opening and one had a prominent probosics positioned in the midline directly superior to the ocular aperture. No external nasal development was noted in the other specimen. The most remarkable finding was the lack of development of all skeletal derivatives of the ethmoidal cartilage(cribriform plate, perpendicular plate, superior and middle nasal conchae, medial orbital walls, and nasal septal cartilage) in both specimens. Since these bones normally form the medial, lateral, and superior walls of the nasal passage, this cavity was also absent. The two posterior halves of the maxillae were directed superiorly, medially, and with the vomer merged in the midline as a thick mass of bone. As a result the right and left alveolar portions of the maxillae were joined superiorly in the midline. With the absence of the nasal cavity, the right and left medial pterygoid plates merged medially with the palatal and pyramidal processes of the palatine bone to obstruct the junction between the oropharynx and nasopharynx(choanal atresia). The role of the skeletal parts of the ethmoid during maxillofacial growth and development is discussed.

Topics: Abnormalities, Multiple; Abnormalities, Severe Teratoid; Bone and Bones; Bone Development; Brain; Eye; Eye Abnormalities; Female; Humans; Infant, Newborn; Male; Nose

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: Congenital Abnormalities; Craniosynostoses; Diagnosis, Differential; Ear; Eye Abnormalities; Eye Color; Female; Hair; Hair Color; Humans; Hypertelorism; Infant, Newborn; Male; Mouth Abnormalities; Nose

Topics: Abnormalities, Multiple; Brain; Eye Abnormalities; Face; Head; Humans; Infant, Newborn; Nose

Two males, 9-11 and 29-31 years of age, with severe hypoplasia of the nose, hypoplasia of the eyes, sensory abnormalities of taste and smell, and hypogonadism were studied. The nasal septum, cribriform plates and foramina of the vomeronasal (vn) nerves were demonstrated in both; the capsule of the vn organ was shown in one. Their nasal skeleton, demonstrated by tomoradiography, had grown in early embryological form. The nose was not patent in either patient. In both, the cranial vaults, orbits, epipharynges, and oral cavities were indented toward the hypoplastic nasal composite and the peripheral dimensions of their faces were normal for their respective ages. Each patient had impaired visual function with cataracts and colobomata. Each was unable to recognize the smell of any vapor (Type I hyposmia), and had severe impairment of recognition of any tastant (recognition hypogeusia); detection of vapors and of tastants were in appropriate anatomical areas. Each was unable orally to recognize standard plastic forms (astereognosis) though each could recognize the forms manually. Each patient had bilateral inguinal hernias, one or two undescended testes, and hypogonadotrophic hypogonadism. These patients do not fall within the spectrum of arrhinencephaly because of the presence of medial structure of attachment of the falx cerebri and because of their normal intelligence. Distinction of patients with this pattern of abnormalities from arrhinencephaly is important by reason of their potentiality of normal mental development. We hypothesize that their abnormalities resulted from an embryological disruption that occurred in the first trimester of pregnancy. The embryogenesis of the nasal composite is presumed to have been adequate for reciprocal induction of the anlagen of the forebrain. Development of their faces to normal peripheral dimensions indicates that the nasal composite is not essential for gross facial enlargement.

Topics: Adult; Child; Eye Abnormalities; Facial Bones; Gonadotropins; Humans; Hypogonadism; Male; Nose; Olfaction Disorders; Skull; Stereognosis; Taste Disorders; Tomography, X-Ray; Vision Disorders

Topics: Abnormalities, Multiple; Animals; Eye Abnormalities; Facial Bones; Female; Nose; Sheep; Sheep Diseases

A patient with hypotelorism, nasomaxillary hypoplasia and cleft lip and palate is presented. The absence of an associated intracranial abnormality, mental retardation or seizures places this patient in a separate category from those described by deMyer. Her intelligence is above normal but at four years of age, she is having psychological problems and difficulties interacting with her peers.

Topics: Child, Preschool; Cleft Lip; Cleft Palate; Eye Abnormalities; Follow-Up Studies; Humans; Infant; Infant, Newborn; Intelligence; Male; Maxilla; Nose; Skull

Nine patients with aberrations in development and placement of the eyes and periocular structures who also had serious defects in central nervous system development were evaluated in order to better understand normal ocular development. Included were an incompletely developed twin stillborn infant who lacked both eyes and the nose, a stillborn infant with cyclopia hypognathia, 6 spontaneous abortuses with varying degrees of holoprosencephaly, and a 17-year-old male with a serious defect in central nervous system development whose right eye was positioned laterally above the right ear. In all cases, evidence indicates that orbital and periocular structures are determined by the underlying optic vesicle rather than independently derived as has been suggested by previous studies.

Topics: Abnormalities, Severe Teratoid; Adolescent; Anophthalmos; Central Nervous System; Diseases in Twins; Eye; Eye Abnormalities; Female; Fetal Death; Head; Humans; Infant, Newborn; Male; Nose; Orbit; Pregnancy

Topics: Abnormalities, Drug-Induced; Adolescent; Dwarfism; Epilepsy; Eye Abnormalities; Female; Fingers; Humans; Hydantoins; Nose; Pregnancy; Pregnancy Complications; Skull

Anomalies of the nose, larynx and oral cavity are described in two patients with cryptophthalmos. A teratogen acting at the time of lid fold formation is probably responsible for the ocular and systemic involvement which are primarily ectodermal defects with some mesodermal involvement.

Topics: Abnormalities, Multiple; Child, Preschool; Eye Abnormalities; Female; Humans; Infant; Larynx; Mouth Abnormalities; Nose; Syndrome; Tongue

Topics: Abnormalities, Multiple; Adult; Child, Preschool; Eye Abnormalities; Humans; Infant; Male; Nose; Syndactyly; Tooth Abnormalities

A translocation 2/6 inherited for 3 generations is described. The propositus, carrier of a partial trisomy 2p, showed multiple morphological anomalies of which microphtalmus and persistance of primary vitreous body were of particular interest. Based on a comparison of this with seven other patients in the literature, the most characteristic clinical symptoms of partial trisomy 2p are concluded to be the following: abundant lanugo at birth, glabella prominence, anteverted nares, dermatoglyphic anomalies, and malformations of the eyes.

Topics: Abnormalities, Multiple; Chromosomes, Human, 1-3; Chromosomes, Human, 6-12 and X; Cytogenetics; Dermatoglyphics; Eye Abnormalities; Hair; Humans; Infant; Male; Microphthalmos; Nose; Psychomotor Disorders; Translocation, Genetic; Trisomy

Topics: Abnormalities, Multiple; Adolescent; Coloboma; Eye Abnormalities; Eyelids; Female; Humans; Infant; Male; Nose; Surgery, Plastic

Topics: Animals; Dog Diseases; Dogs; Eye Abnormalities; Male; Nose; Orbit

Topics: Abnormalities, Multiple; Albinism; Child; Child, Preschool; Deafness; Diagnosis, Differential; Eye Abnormalities; Eye Color; Eyebrows; Female; Hair Color; Humans; Infant; Infant, Newborn; Nose; Waardenburg Syndrome

Since 1872 more than 50 cases of the cryptophthalmos syndrome have been reported. In addition to other deformities, the typical anomalies of this syndrome are the missing palpebral fissure, eyebrow and the rudimentary eyeball. This paper deals with the possibilities of operative correction in a 13-year-old female. We are of the opinion that by means of plastic surgery, social integration into the community of the patient is possible.

Topics: Abnormalities, Multiple; Adolescent; Ear; Eye Abnormalities; Female; Humans; Maxilla; Nose; Ophthalmologic Surgical Procedures; Syndactyly; Syndrome

An 8-month-old infant boy with median facial cleft syndrome had eyelid coloboma, symblepharon, and a cytic mass in the left upper eyelid. The mass proved to be an ectatic cornea containing a large cystic lens. Maldevelopment of the entire anterior segment of the eye was also present, although the posterior globe was well formed. We postulate that an area of localized abnormal mesodermal differentiation and fusion at the 17- to 20-mm stage of development served as a common mechanism for all the defects noted.

Topics: Abnormalities, Multiple; Cleft Lip; Cleft Palate; Coloboma; Cornea; Craniofacial Dysostosis; Eye; Eye Abnormalities; Eyelids; Face; Hair; Humans; Hypertelorism; Infant; Male; Nose; Nose Deformities, Acquired; Orbit; Skull; Syndrome; Tissue Adhesions

An infant who died in the perinatal period with the unusual association of trisomy 18 and cebocephaly is described. It is suggested that this association may be more common than is generally recognised because the majority of such infants are stillborn or live only briefly and often do not have chromosome studies performed.

Topics: Brain; Chromosomes, Human; Chromosomes, Human, 16-18; Cytological Techniques; Eye Abnormalities; Genetic Techniques; Humans; Infant, Newborn; Karyotyping; Male; Nose; Quinacrine; Trisomy

Topics: Abnormalities, Multiple; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, 13-15; Coloboma; Eye Abnormalities; Humans; Infant; Karyotyping; Male; Mouth Abnormalities; Nose; Translocation, Genetic; Trisomy

Topics: Abnormalities, Severe Teratoid; Eye; Eye Abnormalities; Facial Bones; Ganglia; Humans; Infant, Newborn; Mesoderm; Nasal Septum; Nervous System; Nose; Nose Deformities, Acquired; Olfactory Nerve; Telencephalon

Topics: Abnormalities, Multiple; Animals; Eye Abnormalities; Maxilla; Nose; Swine; Swine Diseases

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Abnormalities, Severe Teratoid; Brain; Cortisone; Eye Abnormalities; Facial Bones; Female; Humans; Infant, Newborn; Male; Nose; Pregnancy; Pregnancy Complications, Infectious; Salicylates; Virus Diseases

Topics: Achondroplasia; Bone and Bones; Cartilage Diseases; Cleft Palate; Diagnosis, Differential; Dwarfism; Eye Abnormalities; Female; Humans; Infant, Newborn; Karyotyping; Limb Deformities, Congenital; Nose; Ossification, Heterotopic; Radiography

Topics: Abnormalities, Multiple; Brain; Chromosomes, Human, 13-15; Eye Abnormalities; Face; Humans; Infant, Newborn; Karyotyping; Male; Nose; Orbit; Trisomy

Topics: Abnormalities, Severe Teratoid; Adult; Cerebral Cortex; Cleft Palate; Eye Abnormalities; Face; Facial Bones; Female; Head; Humans; Infant, Newborn; Limbic System; Male; Microphthalmos; Nose; Pedigree; Pregnancy; Telencephalon

Topics: Cephalometry; Dental Occlusion; Eye Abnormalities; Female; Head; Humans; Male; Malocclusion; Mandibulofacial Dysostosis; Maxillofacial Development; Mouth Abnormalities; Nose; Radiography; Somatotypes

Topics: Abnormalities, Multiple; Child, Preschool; Clitoris; Diabetes Mellitus; Dwarfism; Endocrine System Diseases; Eye Abnormalities; Female; Germany, West; Heart Defects, Congenital; Humans; Hyperinsulinism; Hypertrichosis; Kidney; Lip; Nose; Ovary; Progeria

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

Topics: Child; Consanguinity; Ear; Eye Abnormalities; Female; Humans; Malocclusion; Mandibulofacial Dysostosis; Nose; Retrognathia

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: Brain; Eye Abnormalities; Gonads; Humans; Kallmann Syndrome; Nervous System Malformations; Nose; Turner Syndrome

Topics: Abnormalities, Multiple; Child; Consanguinity; Cryptorchidism; Eye Abnormalities; Eye Enucleation; Eyelids; Hernia, Umbilical; Humans; Hydrophthalmos; Male; Microphthalmos; Nose; Penis

Topics: Deafness; Eye Abnormalities; Hearing Loss; Humans; Medical Records; Nose; Waardenburg Syndrome

Topics: Cleft Palate; Eye Abnormalities; Eyebrows; Humans; Lacrimal Apparatus; Nose; Waardenburg Syndrome