title: Split hand/split foot malformation with hearing loss: first report of families linked to the SHFM1 locus in 7q21.
abstract: Developmental anomalies of the appendicular skeleton are among the most common and easily ascertained birth defects. Split hand/split foot malformations, distinctive in having deficiency of the central rays, occur as isolated anomalies and as one component of multisystem syndromes. The clinical and molecular characterization of a new syndrome, found in two unrelated families, consisting of split foot with hearing loss, is presented here. As in other split hand/split foot conditions, variable expression and reduced penetrance is notable. In the larger family, variably expressed split foot malformations were found in 6 of 11 gene carriers. and mild-to-moderate sensorineural hearing loss in 4. Split hand and cleft lip/palate in one individual and tibial deficiency in another suggest that these malformations are uncommon components of the syndrome. Ectodermal abnormalities did not occur. In the second family, variable split foot was observed in 3 of 4 gene carriers, and sensorineural deafness was present in 3. Split hand was only seen in a gene carrier who also had split foot and deafness. One gene carrier only had deafness. The gene for split hand split foot with sensorineural hearing loss was linked to markers in 7q21 in both families, with a combined (maximum LOD score of 4.37 at theta = 0.0 for locus D7S527) at 80% penetrance. Efforts to identify the responsible gene have not yet been successful.
authors.affiliation: JC Self Research Institute, Greenwood Genetic Center, SC 29646, USA.
authors.forename: D
authors.initials: D
authors.lastname: Tackels-Horne
authors.forename: A
authors.initials: A
authors.lastname: Toburen
authors.forename: E
authors.initials: E
authors.lastname: Sangiorgi
authors.forename: F
authors.initials: F
authors.lastname: Gurrieri
authors.forename: X
authors.initials: X
authors.lastname: de Mollerat
authors.forename: R
authors.initials: R
authors.lastname: Fischetto
authors.forename: F
authors.initials: F
authors.lastname: Causio
authors.forename: K
authors.initials: K
authors.lastname: Clarkson
authors.forename: R E
authors.initials: RE
authors.lastname: Stevenson
authors.forename: C E
authors.initials: CE
authors.lastname: Schwartz
mesh_terms: D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging / Q000235:genetics*; D000328:Adult; D002648:Child; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D003638:Deafness / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005532:Foot Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006228:Hand Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011859:Radiography
chemical_list: D005819:Genetic Markers