A novel acropectoral syndrome maps to chromosome 7q36

F syndrome (acropectorovertebral syndrome) is a dominantly inherited skelet al dysplasia affecting the hands, feet, sternum, and lumbosacral spine, whi ch has previously been described in only two families. Here we report a six generation Turkish family with a related but distinct dominantly inherited acropectoral syndrome. All 22 affected subjects have soft tissue syndactyl y of all fingers and all toes and 14 also have preaxial polydactyly of the hands and/or feet. In addition, 14 have a prominent upper sternum and/or a blind ending, inverted U shaped sinus in the anterior chest wall. Linkage s tudies and haplotype analysis carried out in 16 affected and nine unaffecte d members of this family showed that the underlying locus maps to a 6.4 cM interval on chromosome 7q36, between EN2 and D7S2423, a region to which a l ocus for preaxial polydactyly and triphalangeal thumb-polysyndactyly has pr eviously been mapped. Our findings expand the range of phenotypes associate d with this locus to include total soft tissue syndactyly and sternal defor mity, and suggest that F syndrome may be another manifestation of the same genetic entity. In mice, ectopic expression of the gene Sonic hedgehog (Shh ) in limb buds and lateral plate mesoderm during development causes preaxia l polydactyly and sternal defects respectively, suggesting that misregulati on of SHH may underlie the unusual combination of abnormalities in this fam ily. A recently proposed candidate gene for 7q36 linked preaxial polydactyl y is LMBR1, encoding a novel transmembrane receptor which may be an upstrea m regulator of SHH.