Acrocallosal syndrome

Acrocallosal syndrome is an autosomal recessive disorder of brain malformation and complex polydactyly. We report on an additional patient with this disorder. It is suggested that increased birth weight and cerebellar hypoplasia occur in acrocallosal syndrome. The finding of an extra bone within the anterior fontanel in our patient suggests similarity to the Xt mouse mutant, which is homologous to Greig syndrome in man. This provides additional support for the hypothesis of allelism of the Greig and acrocallosal syndromes.     

Acrocallosal syndrome: report of a Brazilian girl.

We report on a Brazilian girl born to nonconsanguineous parents and presenting with frontonasal dysostosis, callosal agenesis, abnormal upper lids, cleft lip/palate, redundant skin in the neck, grooved chin, and bifid thumbs. Major diagnostic criteria present in this patient are related to the acrocallosal syndrome. The clinical and major nosologic aspects of this condition are discussed.     

Greig cephalopolysyndactyly syndrome with dysgenesis of the corpus callosum in a Bedouin family

We report on the first known Bedouin family with Greig cephalopolysyndactyly syndrome (MIM 175700). The index patient and his father shared pre- and postaxial polysyndactyly, mild mental retardation, and corpus callosum dysgenesis. Their phenotypic findings were compared with reported cases of both Greig cephalopolysyndactyly (GCPS) and acrocallosal syndromes. This family represents the second report of the rare occurrence of dysgenesis of the corpus callosum in GCPS. © 1996 Wiley-Liss, Inc.     

Marden-Walker-like syndrome without psychomotor retardation: Report of a Brazilian girl born to consanguineous parents

We report on a Brazilian girl, born to consanguineous parents and presenting a multiple congenital anomaly (MCA) syndrome, mainly characterized by blepharophimosis, cleft palate, and arachnodactyly. The clinical aspects involving this patient suggest an apparently undescribed “new” autosomal recessive syndrome.     

Urinary tract involvement in EEC syndrome: A clinical study in 25 Brazilian patients

We have evaluated 25 patients (14 isolated and 11 familial cases) with the EEC syndrome for genitourinary (GU) tract anomalies through intravenous pyelogram (IVP), voiding urethrocystography, and sonographic examination. Fifty-two percent of the patients (7 isolated and 6 familial cases) had involvement of the urinary tract, with no significant difference between isolated and familial cases. The present data seem to reflect the best estimate of the prevalence of genitourinary anomalies in patients with the EEC syndrome. © 1992 Wiley-Liss, Inc.     

Syndromal frontonasal dysostosis in a child with a complex translocation involving chromosomes 3, 7, and 11

We report on a 4-year-old boy with typical frontonasal dysostosis and an apparently balanced de novo translocation involving chromosomes 3, 7, and 11, and four breakpoints. The karyotype was 46,XY,t(7;3)(3;11) (7pter→7q21.3::3q27→3qter;3pter→3q23::11q21→11qter;11pter→11q21::3q23→3q27::7q21.3→7qter). In situ hybridization with a chromosome 3 painting probe confirmed the interpretation from GTG banding. The child had a widow's peak, marked hypertelorism, absence of the nasal tip, and widely separated nares. He also had an atrial septal defect, micropenis, small testes, clubfeet, scoliosis, block C2–4, and structural brain abnormalities on MRI. In review we found two other cases of frontonasal dysostosis with chromosome abnormalities, neither of which was similar to our case. The presence of a denovo (apparently) balanced translocation in our patient may help to locate the gene(s) for frontonasal dysplasia and perhaps other midline craniofacial malformations. © 1995 Wiley-Liss, Inc.     

Ohdo syndrome: report on a Brazilian girl with additional findings

We describe a Brazilian girl presenting Ohdo syndrome with cleft palate and diverticula of the bladder. Gestational history revealed the occurrence of fever for 12 days in the second month of gestation. To our knowledge, cleft palate and urinary abnormalites are hitherto undescribed features of this syndrome. Additional case reports could elucidate the fortuitous or causal association of these signs, the full phenotypic spectrum, as well as the pattern of transmission of the Ohdo syndrome.     

Mandibulofacial dysostosis: Report on two Brazilian families suggesting autosomal recessive inheritance

We report on mandibulofacial dysostosis in 2 brothers born to normal nonconsanguineous parents, and a girl (F = 1/16) born to normal consanguineous parents. Normal clinical, skeletal, audiologic, and cephalometric studies in the parents, as well as the absense of limp anomalies in these children, exclude the autosomal recessive (Nager and Genée-Widemann) mandibulofacial dysostoses. The data of the present patients associated with the few additional reports on mandibulofacial dysostosis recurring in sibs, suggest the possibility of an autosomal recessive Treacher Collins-like mandibulofacial dysotosis. © 1993 Wiley-Liss, Inc.     

Visceral anomalies in the Apert syndrome

We report on visceral anomalies found in 136 patients with Apert syndrome. Autopsies were only performed on 12 of these cases. Thus, the percentage of anomalies found in our patients should be considered a minimum estimate because of the possibility of clinically silent visceral anomalies, minor internal anomalies, and anatomic variations. Cardiovascular and genitourinary anomalies were found most commonly, occurring in 10% and 9.6%, respectively. As expected, complex and multiple cardiac anomalies were frequently associated with early death. Among genitourinary anomalies, hydronephrosis (3%) and cryptorchidism (4.5%, n =; 66 males) occurred most commonly. In contrast, anomalies of the respiratory system (1.5%) and gastrointestinal anomalies (1.5%) occurred with lower frequency. The finding of a solid cartilaginous trachea is particularly important because no case was diagnosed during life but rather, only at autopsy. Because cardiovascular and genitourinary anomalies occur with significant frequency, they should be considered in the workup of all Apert newborn infants. We also recommend MRI study of the trachea in any infant with signs and symptoms of lower respiratory compromise. © 1993 Wiley-Liss, Inc.     

Fronto-nasal dysostosis,callosal agenesis,crossed-fused ectopia,tibial hemimelia,and preaxial polydactyly of feet: Severe expression of the acrocallosal syndrome?

We report on a girl with frontonasal “dysostosis,” callosal agenesis, crossed-fused ectopia, tibial hemimelia, and preaxial polydactyly of feet. This pattern of the developmental defects suggests a severe form of the acrocallosal syndrome. Implications for genetic counselling are discussed. © 1993 Wiley-Liss, Inc.     

Michels syndrome in a Brazilian girl born to consanguineous parents

We report on a Brazilian girl born to consanguineous parents and presenting with craniosynostosis, telecanthus, blepharophi-mosis, blepharoptosis, epicanthus inversus, cleft lip and palate, skeletal defects, and hearing loss. This combination of anomalies appears to constitute the Michels syndrome. © 1995 Wiley-Liss, Inc.     

Metopic and sagittal synostosis in Greig cephalopolysyndactyly syndrome: five cases with intragenic mutations or complete deletions of GLI3

Greig cephalopolysyndactyly syndrome (GCPS) is a multiple congenital malformation characterised by limb and craniofacial anomalies, caused by heterozygous mutation or deletion of GLI3. We report four boys and a girl who were presented with trigonocephaly due to metopic synostosis, in association with pre- and post-axial polydactyly and cutaneous syndactyly of hands and feet. Two cases had additional sagittal synostosis. None had a family history of similar features. In all five children, the diagnosis of GCPS was confirmed by molecular analysis of GLI3 (two had intragenic mutations and three had complete gene deletions detected on array comparative genomic hybridisation), thus highlighting the importance of trigonocephaly or overt metopic or sagittal synostosis as a distinct presenting feature of GCPS. These observations confirm and extend a recently proposed association of intragenic GLI3 mutations with metopic synostosis; moreover, the three individuals with complete deletion of GLI3 were previously considered to have Carpenter syndrome, highlighting an important source of diagnostic confusion.     

GLI3‐related polydactyly: a review

GLI3 mutations are known to be associated with nine syndromes/conditions in which polydactyly is a feature. In this review, the embryology, pathogenesis, and animal models of GLI3‐related polydactyly are discussed first. This is followed by a detailed review of the genotype–phenotype correlations. Based on our review of the literature and our clinical experiences, we recommend viewing GLI3‐related syndromes/conditions as four separate entities; each characterized by a specific pattern of polydactyly. These four entities are: the preaxial polydactyly type IV‐Greig‐acrocallosal spectrum, postaxial polydactyly types A/B, Pallister–Hall syndrome (PHS), and oral‐facial‐digital overlap syndrome. We also provide illustrative clinical examples from our practice including a family with a novel GLI3 mutation causing PHS. The review also introduces the term ‘Forme Fruste’ preaxial polydactyly and gives several conclusions/recommendations including the recommendation to revise the current criteria for the clinical diagnosis of PHS.     

EEC syndrome and genitourinary anomalies: An update

We report on a large family with the ectrodactyly, ectodermal dysplasia, clefting (EEC) syndrome. The clinical manifestations in this family show great variability. Specific genitourinary anomalies were found. The propositus with micturition problems is discussed in detail. A dysplastic bladder epithelium might be the cause of these problems. A remarkable improvement of the complaints was achieved upon treatment with synthetic sulfonated glycosaminoglycans. © 1996 Wiley-Liss, Inc.     

CHARGE syndrome: Report of 47 cases and review

The acronym CHARGE refers to a syndrome of unknown cause. Here we report on 47 CHARGE patients evaluated for the frequency of major anomalies, namely coloboma (79%), heart malformation (85%), choanal atresia (57%), growth and/or mental retardation (100%), genital anomalies (34%), ear anomalies (91%), and/or deafness (62%). In addition, we comment on anomalies observed very frequently in neonates and infants with the CHARGE syndrome, including, minor facial anomalies, neonatal brain stem dysfunction with cranial nerve palsy, and, mostly, internal ear anomalies such as semicircular canal hypoplasia that were found in each patient that could be tested. We propose several criteria for poor survival including male gender, central nervous system and/or oesophageal malformations, and bilateral choanal atresia. No predictive factor regarding developmental prognosis could be identified in our series. A significantly higher mean paternal age at conception together with concordance in monozygotic twins and the existence of rare familial cases support the role of genetic factors such as de novo mutation of a dominant gene or subtle sub-microscopic chromosome rearrangement. Finally, the combination of malformations in CHARGE syndrome strongly supports the view that this multiple congenital anomalies/mental retardation syndrome is a polytopic developmental field defect involving the neural tube and the neural crests cells. Am. J. Med. Genet. 76:402–409, 1998. © 1998 Wiley-Liss, Inc.     

Jarcho-Levin syndrome: Unusual survival in a classical case

Spondylothoracic dysostosis, or Jarcho-Levin syndrome, together with spondylocostal dysostosis, constitute a heterogeneous group of rare disorders characterized by short-neck, short-trunk dwarfism and multiple vertebral anomalies at all levels of the vertebral column. The latter include hemivertebrae, fused, hypoplastic, and “butterfly” vertebrae. In most cases of Jarcho-Levin syndrome, the small size of the thorax causes respiratory death in infancy. This report of a Puerto Rican child with spondylothoracic dysostosis and unusually long survival to 11 years exemplifies the nosologic and prognostic difficulties associated with this syndrome. © 1994 Wiley-Liss, Inc.     

Short stature,Robin sequence,cleft mandible,pre/postaxial hand anomalies,and clubfoot: A new autosomal recessive syndrome

We report on 5 unrelated Brazilian children with short stature, Robin sequence, cleft mandible, pre/postaxial hand anomalies, and clubfoot. Genetic aspects and phenotypic manifestations are compared with those of previous reports of acrofacial dysostoses and with other Robin sequence syndromes. We suspect that these patients present a previously undescribed autosomal recessive syndrome.