The camptodactyly‐arthropathy‐coxa vara‐pericarditis syndrome: Clinical features and genetic mapping to human chromosome 1

Objective To delineate the clinical features in patients with the autosomal recessive camptodactyly‐arthropathy‐coxa vara‐pericarditis syndrome (CACP) and to determine the location of the involved gene. Methods Eight affected individuals (ages 2‐15 years) with CACP from 4 consanguineous kindreds were clinically evaluated. Four patients are newly described and 4 have been reported previously. Findings were compared with those in 21 other previously reported cases. DNA obtained from the 8 affected patients and their available siblings and parents was used in a genome‐wide search for linkage. Results Congenital camptodactyly and childhood‐onset noninflammatory arthropathy were present in all affected patients. Seven patients developed bilateral coxa vara deformity, and 1 developed coxa magna with cystic erosions. Two of the patients also had symptoms or signs of pericarditis. A genomewide search for linkage identified homozygosity for a series of genetic markers on human chromosome 1q in all affected patients. The marker D1S191 yielded a maximum logarithm of the odds ratio (LOD score) of 3.3 at θ = 0. The CACP gene lies within a 1.9‐cM candidate interval defined by the markers D1S2107 and D1S222. Conclusion The principal features of the CACP syndrome are congenital or early‐onset camptodactyly and childhood‐onset noninflammatory arthropathy. Coxa vara deformity or other dysplasia associated with progressive hip disease may develop over time. Clinical pericarditis may also occur. A locus responsible for causing CACP syndrome is assigned to a 1.9‐cM interval on human chromosome 1q25‐31 by homozygosity mapping. This now facilitates the identification of the responsible gene and permits testing for locus homogeneity in other CACP kindreds.