Spondyloperipheral Dysplasia

A number sign (#) is used with this entry because spondyloperipheral dysplasia is caused by heterozygous mutation in the alpha-1 type II collagen gene (COL2A1; 120140) on chromosome 12q13.

Clinical Features

Kelly et al. (1977) described a father and 2 children (son and daughter) with an identical skeletal dysplasia of unusual type. It fell generally in the category of spondyloepiphyseal dysplasias. Platyspondyly and severe hip changes were present. The hands and feet were very short as in peripheral dysostosis. The ulna was very short distally, so that it showed deficiency at the wrist. Some of the metatarsals were particularly short. The father was 144 cm tall; the 31-year-old daughter was 142 cm tall; and the 30-year-old son was 154 cm tall. The pedigree was equally consistent with autosomal dominant or autosomal recessive inheritance because the affected father was married to his first cousin and came himself from a consanguineous mating. The families reported by Sybert et al. (1979) and by Vanek (1983) have some similarities; in these families, inheritance seems to have been autosomal dominant. The single case reported by Goldblatt and Behari (1987) also has some similarities. The patient was 108 cm tall at the age of 20, with an arm span of 125.5 cm; the forearms showed mild bilateral bowing. The shortening of the bones of the hands and feet was possibly more striking in the patients reported by Kelly et al. (1977).

Sorge et al. (1995) described the disorder in a mother and 3 of her children, 2 daughters and a son. In addition to platyspondyly with endplate indentations and brachydactyly, the proband had a characteristic, 'pugilistic' face, sensorineural deafness, and mental retardation.

Zankl et al. (2004) reported 2 patients with findings similar to those described by Zabel et al. (1996): clubfeet, midface hypoplasia, early-onset high grade myopia, platyspondyly, epiphyseal dysplasia, and brachydactyly E-like changes developing in childhood.

Molecular Genetics

Zabel et al. (1996) described a 5-bp duplication in exon 51 of the COL2A1 gene (120140.0030) resulting in a frameshift in a patient with what they concluded was the same disorder as that reported by Kelly et al. (1977), Vanek (1983), Sybert et al. (1979), and Sorge et al. (1995).

In 2 patients with findings similar to those described by Zabel et al. (1996), Zankl et al. (2004) identified heterozygous truncating mutations in the COL2A1 gene (120140.0041 and 120140.0042).