Gracile bone dysplasia
Overview
Gracile bone dysplasia: An inherited disorder characterized by brittle bones and thin, slender long bones and ribs as well as other abnormalities.
Symptoms
Features of GCLEB include premature closure of basal sutures, cloverleaf skull deformity due to underossified bone with resultant soft tissue protrusion, deficient calvarial mineralization, flared metaphyses and fractures. Patients with KCS2 are small at birth, have delayed closure of the anterior fontanelle and hyperopia. Episodic hypocalcemic tetany and convulsions are common. The psychomotor development of KCS2 patients is usually normal unlike the autosomal recessive form of KCS (KCS1; MIM 244460), which is caused by mutations in the TBCE gene.
Causes
In 5 patients with gracile bone dysplasia and 5 patients with autosomal dominant Kenny-Caffey syndrome (KCS2; 127000), Unger et al. (2013) identified heterozygosity for 6 mutations in the FAM111A gene. In the 7 families in which DNA was available from both parents, the mutations were confirmed to have arisen de novo. None of the mutations was found in the 1000 Genomes Project or NHLBI Exome Variant Server databases. The authors concluded that KCS2 and gracile bone dysplasia represent allelic disorders of differing severity.