The Epidemiology, Genetics and Future Management of Syndactyly

Syndactyly is a condition well documented in current literature due to it being the most common congenital hand defect, with a large aesthetic and functional significance

A Clinically Variant Fibrosis Syndrome In A Turkish Family Maps To The Cfeom1 Locus On Chromosome 12

Objectives: To describe the phenotype of a Turkish family with variably expressed congenital fibrosis of the extraocular muscles (CFEOM), and to determine the genetic location of their disorder. Methods: Participants were examined and had blood extracted for genetic analysis. The clinical features of the family's disorder were studied, and the disorder was tested for linkage to the 3 known CFEOM loci (CFEOM1, CFEOM2; and CFEOM3). Results: Twenty-nine affected and 31 unaffected family members participated in the study. Eighteen affected individuals had congenital bilateral ptosis and restrictive infraductive (downward) ophthalmoplegia, consistent with the published descriptions of classic CFEOM families linked to the CFEOM1 locus. Eleven affected individuals, however, had eye(s) in a neutral primary position, residual upgaze, and/or absence of ptosis, thus deviating from previous descriptions of CFEOM1-linked families. Analysis of the autosomal dominant variably expressed disorder in this family revealed linkage to the CFEOM1 locus on chromosome 12 with a maximum lod score of 10.8 at D12S85. Conclusions: This Turkish Family segregates a variably expressed form of CFEOM that most closely resembles CFEOM3-linked CFEOM, but maps to the CFEOM1 locus. Clinical Relevance: These data establish that there is much greater phenotypic heterogeneity at the CFEOM1 locus than previously reported, and this may blur our ability to distinguish the different CFEOM loci based solely on clinical presentation.WoSScopu

Dach: Genomic Characterization, Evaluation As A Candidate For Postaxial Polydactyly Type A2, And Developmental Expression Pattern Of The Mouse Homologue

The gene DACH is a human homologue of Drosophila melanogaster dachshund (dac), which encodes a nuclear factor essential for determining cell fates in the eye, leg, and nervous system of the fly. To investigate possible connections between DACH and inherited developmental disorders, we have characterized the human DACH genomic structure and investigated the tissue and cellular distribution of the mouse DACH1 protein during development. DACH spans 400 kb and is encoded by 12 exons. The predominant DACH transcript is 5.2 kb and encodes a 706-amino-acid protein with an observed molecular weight of 97 kDa. DACH mRNA was defected in multiple adult human tissues including kidney and heart. The mouse DACH1 protein was immunolocalized to specific cell types within the developing kidneys, eyes, cochleae, and limb buds. Data suggest genetic linkage of the limb bud patterning defect postaxial polydactyly type A (designated PAP-A2, MIM 602085) to a 28-cM interval on chromosome 13 that includes DACH. However, mutation analysis of DACH in this PAP-A2 pedigree revealed no sequence differences in the coding region, splice sites, or proximal promoter region. The data presented will allow for the analysis of DACH as a candidate for other developmental disorders affecting the limbs, kidneys, eyes, ears, and other sites of DACH expression.Wo

Type II familial synpolydactyly: report on two families with an emphasis on variations of expression

Type II familial synpolydactyly is rare and is known to have variable expression. However, no previous papers have attempted to review these variations. The aim of this paper was to review these variations and show several of these variable expressions in two families. The classic features of type II familial synpolydactyly are bilateral synpolydactyly of the third web spaces of the hands and bilateral synpolydactyly of the fourth web spaces of the feet. Several members of the two families reported in this paper showed the following variations: the third web spaces of the hands showing syndactyly without the polydactyly, normal feet, concurrent polydactyly of the little finger, concurrent clinodactyly of the little finger and the ‘homozygous' phenotype. It was concluded that variable expressions of type II familial synpolydactyly are common and awareness of such variations is important to clinicians

Hereditary motor and sensory neuropathy with congenital glaucoma: report on a family Neuropatia hereditária sensitivo-motora com glaucoma congênito: descrição de uma família

We report three siblings of a family with hereditary motor and sensory polyneuropathy (HMSN) and buphthalmos. Electrophysiological studies showed a demyelinating neuropathy and pathological findings showed severe loss of myelinated fibers (MF), thin myelin sheaths and myelin infoldings in a few remaining MF. The presumed mode of inheritance is autosomal recessive. This family probably represents an unique form of CMT4 that may be related to one of the congenital glaucoma genic locus, particularly GLC3A and GLC3B, described in Turkish families.<br>Descrevemos três membros afetados de uma família com neuropatia hereditária sensitivo-motora tipo I (desmielinizante) e glaucoma congênito (buftalmia). O estudo eletrofisiológico dos membros afetados demonstrou polineuropatia sensitivo-motora desmielinizante, com ausência ou redução acentuada das velocidades de neurocondução sensitiva e motora. A biópsia do nervo sural revelou redução moderada a grave das fibras mielinizadas, bainhas de mielina de espessura diminuída (remielinização) com dobramentos delas nas poucas fibras mielinizadas remanescentes. Não foram observadas formações em casca de cebola, nem tampouco alterações hipertróficas. O padrão de herança desta família parece ser autossômico recessivo. Sugerimos tratar-se de uma forma singular de doença de Charcot-Marie-Tooth autossômica recessiva (CMT4), que eventualmente pode possuir locus gênico próximo a um dos locus do glaucoma congênito (GLC3A e GLC3B), localizados nos cromossomos 2p21 e 1p36

A new locus for postaxial polydactyly type A/B on chromosome 7q21-q34.

Item does not contain fulltextPostaxial polydactyly (PAP) is the occurrence of one or more extra ulnar or fibular digits or parts of it. In PAP-A, the extra digit is fully developed and articulates with the fifth or an additional metacarpal/metatarsal, while it is rudimentary in PAP-B. Isolated PAP usually segregates as an autosomal dominant trait, with variable expression. Three loci are known for PAP in humans. PAPA1 (including PAP-A/B in one patient) on 7p13 caused by mutations in the GLI3 gene, PAPA2 on 13q21-q32 in a Turkish kindred with PAP-A only, and a third one (PAPA3) in a Chinese family with PAP-A/B on 19p13.1-13.2. We identified a fourth locus in a large Dutch six-generation family with 31 individuals including 11 affecteds. Their phenotype varied from either PAP-A, or PAP-B to PAP-A/B with or without the co-occurence of partial cutaneous syndactyly. We performed a whole-genome search and found linkage between PAP and markers on chromosome 7q. The highest LOD score was 3.34 obtained at D7S1799 and D7S500 with multipoint analysis