A newly recognized neuroectodermal syndrome of familial alopecia, anosmia, deafness, and hypogonadism

We describe a large, three generation kindred in which 16 individuals were affected with alopecia, hyposmia or anosmia, conductive deafness associated with protruding ears, microtia, and/or atresia of the external auditory canal, hypogonadotropic hypogonadism due to LH/FSH deficiency, and a greater than normal tendency to dental caries. Variable manifestations include mild facial asymmetry, mental retardation, congenital heart defect, and cleft palate. This seems to be a previously undescribed pleiotropic autosomal dominant trait with variable expressivity. The manifestations can be explained on the basis of involvement of the ectoderm and neuroectoderm of the first and second branchial arches, of Rathke's pouch, and of the diencephalon.     

Autosomal dominant inheritance of Barber-Say syndrome.

We report on a mother-to-son transmission of the Barber-Say syndrome, a finding that strongly supports dominant inheritance of this rare disorder. The characteristic facial changes, small ears, hirsutism, and redundant skin of our patients are consistent with the findings of five reported cases. The mother also had cleft palate and mild conductive hearing loss. Her son had a shawl scrotum, primary hypospadias, and mild hearing loss by report. The inheritance of this rare disorder has not been established. The parent-to-child transmission in this family suggests X-linked or autosomal dominant inheritance. The parents of the patient reported by Santana et al. [1993: Am. J. Med. Genet. 47:20-23] were consanguineous, suggesting autosomal recessive inheritance in other cases.     

Choanal stenosis,hypothelia, deafness,recurrent dacryocystitis,neck fistulas,short stature,and microcephaly: report of a case

We report on a 11-year-old girl with bilateral choanal stenosis, hypothelia, hearing loss, recurrent dacryocystitis, neck fistulas, short stature, and microcephaly. Only three individuals with choanal atresia from a consanguineous family have been reported. One of the patients also had hypoplastic nipples, hypotonia, and delay in speech development. Similar clinical features were seen in two children reported by Greenberg [1987: Am J Med Genet 28:931-934] and Wilson et al. [1998: Am J Med Genet 75:220-222]. They were prenatally exposed to methimazole because of maternal Graves disease. Neck fistulas and microcephaly noted in our patient were not previously reported as features of the syndrome or in the patients prenataly exposed to methimazole. Our patient and those reported by Qazi et al. [1982: Am J Med Genet 13:413-416] most probably have a rare syndrome characterized by this distinctive combination of symptoms. Prenatal exposure to methimazole can cause a phenocopy of the syndrome, which was probably the case in the patients reported by Greenberg and Wilson et al.     

Trichorrhexis Nodosa and lip pits in autosomal dominant ectodermal dysplasia—central nervous system malformation syndrome

A Dandy-Walker-like malformation was observed in a retarded girl who had signs of hidrotic ectodermal dysplasia. This is the third report of the rare triad ectodermal dysplasia-CNS malformation-mental retardation. We observed additional findings, such as submucous cleft palate with lip pits and trichorrhexis nodosa. The proposita's mother had similar hair and facial changes. Two maternal relatives had cleft palate. Autosomal dominant inheritance is suggested. Am. J. Med. Genet. 71:226–228, 1997. © 1997 Wiley-Liss, Inc.     

Rapp-Hodgkin syndrome with palmoplantar keratoderma,glossy tongue,congenital absence of lingual frenum and of sublingual caruncles: Newly recognized findings

We report on a boy with Rapp-Hodgkin syndrome (RHS) or Rapp-Hodgkin ectodermal dysplasia. He had sparse, wiry, slow growing and uncombable hair, but no pili torti or pili canaliculi characteristic of RHS. He also had sparse eyelashes and eyebrows, and obstructed lacrimal puncta and epiphora. Bilateral bony external auditory canal stenosis led to hearing loss. The mouth was small with repaired bilateral cleft lip and palate. Oral manifestations included hypodontia, microdontia, unerupted mandibular premolars with well formed roots, large dental pulp spaces, enamel hypoplasia, multiple caries, glossy tongue, and congenital absence of lingual frenum and of sublingual caruncles including submandibular and sublingual salivary duct openings. Palmoplantar keratoderma, unerupted premolars, congenital absence of lingual frenum, sublingual caruncles, glossy tongue, and pili canaliculi seen in the patient are newly recognized findings of this syndrome. Overlapping findings of RHS ectrodactyly–ectodermal dysplasia–clefting syndrome (EEC), and ankyloblepharon–ectodermal defects–cleft lip and palate syndrome (AEC) are discussed. Am. J. Med. Genet 79:343–346, 1998. © 1998 Wiley-Liss, Inc.     

Autopsy,radiographic, and prenatal ultrasonographic examination of a stillborn fetus with femoral facial syndrome

Femoral facial syndrome (FFS) is comprised of cleft palate, micrognathia, short or absent femora, and vertebral and genitourinary malformations. We report on a stillborn fetus with FFS delivered to a mother with gestational diabetes. Prenatal ultrasound examination showed abnormalities at 21 weeks of gestation; prior ultrasound findings were interpreted as normal. Long bone histology showed disorganization of the growth plate with a relative decrease in cartilaginous matrix and vacuolization and binucleation of the chondrocytes. Am. J. Med. Genet. 71:76–79, 1997. © 1997 Wiley-Liss, Inc.     

Familial CHARGE syndrome: clinical report with autopsy findings

We report on a patient with CHARGE syndrome, as manifested by a coloboma of the optic nerve head, congenital heart defect (ASD, VSD, and parachute mitral valve), choanal atresia, severe growth retardation, genital hypoplasia, abnormal ears, cleft lip and palate, and pectus carinatum. His chromosomes were normal. He died at 19 months. His mother was short and had hearing impairment, choanal atresia, and a coloboma. We suggest that this represents evidence for dominant transmission of this disorder in this family. Other familial cases from the literature are reviewed.     

Prenatal diagnosis and confirmation of the acrofacial dysostosis syndrome type Rodriguez

The group of acrofacial dysostosis (AFD) syndromes is very heterogeneous and contains many different entities. In 1990, Rodriguez et al. [1990: Am J Med Genet 35:484-489] described a new type of AFD characterized by severe mandibular hypoplasia, phocomelia and oligodactyly of the upper limbs, absence of fibulae, microtia, cleft palate, internal organ anomalies including arrhinencephaly and abnormal lung lobulation, and early lethality. We describe another case of AFD type Rodriguez, identified by prenatal ultrasonography at 25 weeks of gestation.     

Severe Hajdu-Cheney syndrome with upper airway obstruction

Hajdu-Cheney syndrome is an autosomal dominant disorder of acroosteolysis, skull deformities, characteristic facial abnormalities, osteoporosis, joint laxity, early loss of teeth, hearing loss, and a hoarse voice. We report on an 8 ½-year-old boy with Hajdu-Cheney syndrome and cystic kidney disease, congenital heart disease, hydrocephalus, cleft lip and palate, hydrosyringomyelia, club feet, splenomegaly, hypospadias, vertebral anomalies, and upper airway obstruction. A review of 44 patients did not uncover any other patients with all of these manifestations, nor any patient with upper airway obstruction. Hajdu-Cheney syndrome appears to encompass a broader phenotype than previously recognized. The documentation of these additional anomalies is valuable because the findings of acroosteolysis and osteoporosis can present later in the course. Am. J. Med. Genet. 70: 261–266, 1997. © 1997 Wiley-Liss, Inc.     

Choanal atresia as a feature of ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome.

We report here a father and daughter with digital abnormalities, nasolacrimal duct obstruction, and variable alopecia. The father had a cleft lip and palate and the daughter had choanal atresia. We propose they both have the EEC syndrome and show the variable expressivity of this disorder. Choanal atresia has not been previously reported in this condition.     

Dominant coloboma-microphthalmos syndrome associated with sensorineural hearing loss,hematuria, and cleft lip/palate

Ocular colobomas and microphthalmos, isolated or as part of a syndrome, are usually sporadic and only rarely found in large families. A 4-generation family with autosomal dominant uveal coloboma and microphthalmos associated with cleft lip and palate was re-evaluated. Wide variability in expression is evident and more recently recognized manifestations include a complete spectrum of eye involvement, impairment of extraocular movement, mid-frequency sensorineural hearing loss, and hematuria. Learning difficulties requiring remedial teaching were present in one third of those affected and a neural tube defect has occurred in one presumed affected member. This family appears to present a unique phenotype, which provides an opportunity to identify a genetic locus involved in eye, ear, renal, primary palate, and brain development. Am. J. Med. Genet. 72:227–236, 1997. © 1997 Wiley-Liss, Inc.     

Tetra-amelia and splenogonadal fusion in Roberts syndrome

Roberts-SC phocomelia syndrome comprises limb deficiencies of variable severity, facial clefts, and other anomalies. Tetra-amelia may also be associated with facial clefts and similar anomalies. We report on a female infant with severe tetra-amelia, micrognathia, cleft palate, splenogonadal fusion, and premature centromere separation. We propose that this represents the severe expression of the Roberts-SC phocomelia syndrome. Am. J. Med. Genet. 68:185–189, 1997 © 1997 Wiley-Liss, Inc.     

Hardikar syndrome: new features

Hardikar syndrome (HS) is a disorder of multiple anomalies predominantly characterized by cleft lip/palate, liver and biliary tract disease, intestinal malrotation, obstructive uropathy, and retinopathy. To date, three patients have been reported with the unusual constellation of chronic liver/biliary tract disease and obvious defects in organogenesis [Hardikar et al. (1992): Am J Med Genet 44: 13-17; Cools and Jaeken (1997): Am J Med Genet 71: 472-474]. With this report, we add another patient with this syndrome. New features, hitherto not reported, were vaginal atresia, a type 1 choledochal cyst and, owing to the progressive nature of the liver disease, the need for liver transplantation. It is intriguing to speculate, that HS could be genetically related to Alagille syndrome (AS), since both conditions share an unusual number of phenotypic abnormalities.     

Unexpected life‐threatening complications in Kabuki syndrome

Kabuki syndrome is a rare multiple congenital anomalies/mental retardation syndrome comprising a distinct facial appearance and fetal fingertip pads. We observed two patients with Kabuki syndrome and describe unusual life‐threatening complications, including stenosis of the central airways (not previously reported), extrahepatic biliary atresia, and congenital diaphragmatic hernia. Am. J. Med. Genet. 94:170–173, 2000. © 2000 Wiley‐Liss, Inc.     

Hemifacial microsomia and abnormal chromosome 22

We report on partial dup(22q), growth deficiency, and the facioauriculovertebral sequence including hemifacial microsomia, cleft lip and palate, preauricular tags, and hearing loss in one patient. No endocrine or systemic cause for growth deficiency was identified. The case illustrates applicability of chromosome analysis in syndrome-associated growth failure, and a previously unreported associated chromosome abnormality. Am. J. Med. Genet. 76:71–73, 1998. © 1998 Wiley-Liss, Inc.     

Oral-facial-digital syndrome with Y-shaped fourth metacarpals and endocardial cushion defect

We report on a boy with pseudo-cleft of the upper lip, cleft palate, bifid uvula, lobulated tongue, hypoplasia of the epiglottis, both preaxial and central polydactyly of the hands (Y-shaped fourth metacarpals), bilateral preaxial polydactyly of the feet, postaxial polydactyly of the left foot, hearing impairment, and congenital heart disease with endocardial cushion defect. These clinical manifestations resembled oral-facial-digital syndrome type II (OFDS II, Mohr syndrome) or type VI (Váradi syndrome), associated with an atrioventricular canal. Clinical variability of OFDS II has been observed repeatedly. To the best of our knowledge, this is the first reported case of OFDS II with Y-shaped fourth metacarpals. In addition to Y-shaped fourth metacarpals, Mohr syndrome plus atrioventricular canal and hypoplasia of the epiglottis may represent an additional subgroup of OFDS. Am. J. Med. Genet. 86: 278–281, 1999. © 1999 Wiley-Liss, Inc.     

Anophthalmia-microphthalmia-oblique clefting syndrome: Confirmation of the Fryns anophthalmia syndrome

We describe a patient with bilateral extreme microphthalmia with bilateral congenital glaucoma, bilateral medial oblique facial cleft ending in lid colobomas, bilateral stenosis of the choanae, bifid uvula, frontal encephalocele, and premature craniosynostosis. The cause is unknown, but the phenotype resembles the Fryns anophthalmia-plus syndrome, which may be a recessive trait, although intrauterine environmental factors cannot be excluded. Am. J. Med. Genet. 73:36–40, 1997. © 1997 Wiley-Liss, Inc.     

Acrocallosal syndrome in Algerian boy born to consanguineous parents: Review of the literature and further delineation of the syndrome

We present a 17-month-old boy with the acrocallosal syndrome. He was born to consanguineous parents. Abnormal findings included agenesis of the corpus callosum, a ventricular septal defect (VSD), postaxial polydactyly of fingers, cleft soft palate, intestinal malrotation, large anterior fontanelle, prominent forehead, hypertelorism, epicanthic folds, short nose and mandible and preauricular skin tags, mixed hearing loss, laryngomalacia, and growth and severe motor and mental retardation. A review of previous reports on the acrocallosal syndrome shows considerable clinical variability; minimal diagnostic criteria are proposed. A developmental field defect with disturbance of midline development is suggested. Am. J. Med. Genet. 69:17–22, 1997. © 1997 Wiley-Liss, Inc.     

Smith-Fineman-Myers syndrome in apparently monozygotic twins

We report on two boys, monozygotic twins born to normal and nonconsanguineous parents, presenting with an unusual facial appearance, cortical atrophy, dolichocephaly, short stature, cleft palate, micrognathia, prominent upper central incisors, bilateral Sidney line, minor foot deformities, unstableness in walking, early hypotonia, hyperreflexia, hyperactivity, psychomotor retardation, and severe delay in language development. These manifestations resemble those previously described in the Smith-Fineman-Myers syndrome. Am. J. Med. Genet. 79:205–208, 1998. © 1998 Wiley-Liss, Inc.