A novel acropectoral syndrome maps to chromosome 7q36

Abstract

F syndrome (acropectorovertebral syndrome) is a dominantly inherited skeletal dysplasia aVecting the hands, feet, sternum, and lumbosacral spine, which 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 aVected subjects have soft tissue syndactyly 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 studies and haplotype analysis carried out in 16 aVected and nine unaVected 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 locus for preaxial polydactyly and triphalangeal thumb-polysyndactyly has previously been mapped. Our findings expand the range of phenotypes associated with this locus to include total soft tissue syndactyly and sternal deformity, 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 preaxial polydactyly and sternal defects respectively, suggesting that misregulation of SHH may underlie the unusual combination of abnormalities in this family. A recently proposed candidate gene for 7q36 linked preaxial polydactyly is LMBR1, encoding a novel transmembrane receptor which may be an upstream regulator of SHH. (J Med Genet 2001;38:304-309)

Acropectoral syndrome

“…Pectus carinatum deformity of the upper sternum alone or an associated pectus excavatum deformity of the lower sternum, sometimes leading to formation of an inverted U-shaped blind sinus in the anterior chest wall constitutes the pectoral component of the syndrome. Linkage studies carried out in affected and unaffected members of this particular family mapped a locus on chromosome 7q36 (Dundar et al, 2001). A similar phenotype associated with acral defects (involving preaxial polydactyly and triphalangeal thumb-polysyndactyly) seen in individuals Photograph showing bifid thumb.…”

“…The only report of this syndrome in the English literature has been in a Turkish family of six generations, reported by Dundar et al (2001). It is described as a dominantly inherited skeletal dysplasia distinct from a related acropectoro-vertebral syndrome reported by Grosse et al (1969) (skeletal dysplasia affecting the limbs, sternum, and lumbosacral spine, also called F-syndrome, OMIM 102510).…”

“…Linkage studies and haplotype analysis carried out in this reported family mapped this disorder to a locus on chromosome 7q36 in common with many other cases of preaxial polydactyly in a region where there is an upstream regulator of SHH (sonic hedgehog) (Dundar et al, 2001;Lettice et al, 2002). In this report, we describe an Indian family showing physical features suggestive of an extended acropectoral syndrome phenotype with variable penetrance.…”

“…Acropectoral syndrome [Online Mendelian Inheritance in Man (OMIM) 605967] is an autosomal dominant skeletal dysplasia syndrome affecting the development of hands or feet and sternum, which is so far described in one family (Dundar et al, 2001). Linkage studies and haplotype analysis carried out in this reported family mapped this disorder to a locus on chromosome 7q36 in common with many other cases of preaxial polydactyly in a region where there is an upstream regulator of SHH (sonic hedgehog) (Dundar et al, 2001;Lettice et al, 2002).…”

Single nucleotide polymorphisms in the chicken Lmbr1 gene are associated with chicken polydactyly

“…The chromosomal region for human PPD was further narrowed down to a 450 kb segment that contains Hlxb9, C7orf2, C7orf3 and C7orf4, but no specific mutations responsible for the PPD expression were detected (Heus et al, 1999). Several other forms of human limb malformation, including complex polysyndactyly (CPS), acheiropodia (ACHP), and acropectoral syndrome, have also been mapped to human Chr 7q36 (Tsukurov et al, 1994;Escamilla et al, 2000;Dundar et al, 2001).…”