Autosomal dominant spondylocarpotarsal synostosis syndrome: Phenotypic homogeneity and genetic heterogeneity

• Published in: American journal of medical genetics. Part A 2008-06, Vol.146A (12), p.1593-1597
• Main Authors: Isidor, B., Cormier‐Daire, V., Le Merrer, M., Lefrancois, T., Hamel, A., Le Caignec, C., David, A., Jacquemont, S.
• Format: Article
• Language: English
• Subjects: Adult; autosomal dominant; Biological and medical sciences; block vertebrae; carpal fusion; Child; Contractile Proteins - genetics; Female; Filamins; Genes, Dominant; Hand Deformities - diagnostic imaging; Hand Deformities - genetics; Humans; Male; Medical genetics; Medical sciences; Microfilament Proteins - genetics; Mutation; Pedigree; Phenotype; Radiography; short stature; Spine - abnormalities; Spine - diagnostic imaging; spondylocarpotarsal synostosis syndrome; Synostosis - diagnostic imaging; Synostosis - genetics; Tarsal Bones - abnormalities; Tarsal Bones - diagnostic imaging; vertebral unsegmented bar
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.32217

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. © 2008 Wiley‐Liss, Inc.