Exclusion of the Ellis-van Creveld region on chromosome 4p16 in some families with asphyxiating thoracic dystrophy and short-rib polydactyly syndromes

Ellis-van Creveld syndrome (EVC) is a relatively rare, usually non-lethal, autosomal recessive skeletal dysplasia characterized by short stature, poly dactyly, cardiac and renal anomalies. Linkage analysis has localized the di sease gene to chromosome 4p16, with the markers at loci D4S827 and D4S3135 defining the centromeric and telomeric limits of the linked interval, respe ctively. There has been long-term speculation that asphyxiating thoracic dy strophy (ATD) and the short-rib polydactyly syndromes (SRP) represent the s evere end of the EVC disease spectrum. We performed linkage analysis using markers from the EVC region in seven families manifesting either ATD or SRP type ill. In two of the families, one segregating ATD and one SRP kindred, linkage of the phenotype to the EVC region was excluded. In the other five families linkage of the phenotype to the EVC region could not be excluded, but the families were too small for linkage to the region to be establishe d. The exclusion of the EVC region in ATD and SRP III families suggests tha t locus heterogeneity exists within the short-rib dysplasia (with and witho ut polydactyly) group of disorders.