title: Autosomal dominant spondylocarpotarsal synostosis syndrome: phenotypic homogeneity and genetic heterogeneity.
abstract: Spondylocarpotarsal synostosis syndrome (SCT) (OMIM 272460), originally thought to be a failure of normal spine segmentation, is characterized by progressive fusion of vertebras and associates unsegmented bars, scoliosis, short stature, carpal and tarsal synostosis. Cleft palate, sensorineural or mixed hearing loss, joint limitation, clinodactyly, and dental enamel hypoplasia are variable manifestations. Twenty-five patients have been reported. Thirteen affected individuals were siblings from six families and four of these families were consanguineous. In four of those families, Krakow et al. [Krakow et al. (2004) Nat Genet 36:405-410] found homozygosity or compound heterozygosity for mutations in the gene encoding FLNB. This confirmed autosomal recessive inheritance of the disorder. We report on two new patients (a mother and her son) representing the first case of autosomal dominant inheritance. These patients met the clinical and radiological criteria for SCT and did not present any features which could exclude this diagnosis. Molecular analysis failed to identify mutations in NOG and FLNB. SCT is therefore, genetically heterogeneous. Both dominant and autosomal recessive forms of inheritance should be considered during genetic counseling.
authors.affiliation: Service de Génétique Médicale, Nantes University Hospital, Nantes, France. bertrand.isidor@chu-nantes.fr
authors.forename: B
authors.initials: B
authors.lastname: Isidor
authors.forename: V
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: M
authors.initials: M
authors.lastname: Le Merrer
authors.forename: T
authors.initials: T
authors.lastname: Lefrancois
authors.forename: A
authors.initials: A
authors.lastname: Hamel
authors.forename: C
authors.initials: C
authors.lastname: Le Caignec
authors.forename: A
authors.initials: A
authors.lastname: David
authors.forename: S
authors.initials: S
authors.lastname: Jacquemont
mesh_terms: D000328:Adult; D002648:Child; D003285:Contractile Proteins / Q000235:genetics; D005260:Female; D064448:Filamins; D005799:Genes, Dominant; D006226:Hand Deformities / Q000000981:diagnostic imaging* / Q000235:genetics*; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011859:Radiography; D013131:Spine / Q000002:abnormalities* / Q000000981:diagnostic imaging*; D013580:Synostosis / Q000000981:diagnostic imaging* / Q000235:genetics*; D013639:Tarsal Bones / Q000002:abnormalities* / Q000000981:diagnostic imaging*
chemical_list: D003285:Contractile Proteins; C578662:FLNB protein, human; D064448:Filamins; D008840:Microfilament Proteins