Cousin Syndrome

A number sign (#) is used with this entry because of evidence that Cousin syndrome is caused by homozygous mutation in the TBX15 gene (604127) on chromosome 1p12.

Clinical Features

Among the 7 children of first-cousin Maghrebian parents, Cousin et al. (1982) described a brother and sister with a disorder consisting of congenital dwarfism, facial dysmorphism, and several skeletal anomalies, most strikingly bilateral agenesis of the alae (wings) of the scapula and hypoplasia of the alae of the ilium and acetabulum, resulting in hip dislocation. An auricular anomaly and cervical cutaneous diverticulum were illustrated. Moderate psychomotor retardation was also present. Cousin et al. (1982) suggested that this may represent a new autosomal recessive disorder.

The apparently recessive disorder reported by Elliott et al. (2000) as scapuloiliac dysostosis (see 169550) may be the same disorder as that reported by Cousin et al. (1982). Pelvis-shoulder dysplasia (169550) is a dominantly inherited condition with hypoplasia of the scapula and pelvis but with no craniocervical malformation.

Lausch et al. (2008) described 2 unrelated girls with Cousin syndrome, each born to consanguineous parents. Physical features included frontal bossing, narrow palpebral fissures with deep set globes and hypertelorism, strabismus, low set and posteriorly rotated ears, a short neck with redundant skin folds, and a low hairline. Skeletal features included fixed flexion at the elbow joints and leg shortening secondary to bilateral dislocation of the hips and hip flexion. Radiographic findings were hypoplastic scapulae and iliac bones, short femurs, humeroradial synostosis, and moderate brachydactyly. Both girls had normal intelligence. One patient had been given a diagnosis of campomelic dysplasia (114290); the other patient had been diagnosed with pelvis-shoulder dysplasia.

Molecular Genetics

By sequence analysis of the TBX15 gene in 2 unrelated girls with Cousin syndrome, Lausch et al. (2008) identified homozygosity for a different single-nucleotide deletion in each girl (604127.0001-604127.0002). Both deletions occurred at codon 344.

Animal Model

Lausch et al. (2008) identified the Tbx15-deficient mouse phenotype as a possible model of Cousin syndrome. Similar features included small overall size, hypoplastic scapula, and abnormalities of the cranial bones and cervical vertebrae.