Expanding the Clinical Spectrum of Cousin Syndrome: A Novel Biallelic Missense Variant in TBX15 Causing a Milder Phenotype.

Abstract

Cousin syndrome is a rare skeletal dysplasia characterized by distinctive facial features, humeroradial synostosis, and hypoplasia of the ilia and scapula. Since the original description of the phenotype in two cases by Cousin in 1982, only three additional cases have been published. A molecular origin was found in homozygous truncating mutations in TBX15, a member of the T-box gene family that encodes transcription factors regulating the developing limb buds. Here we present a sixth patient with a biallelic novel missense variant in TBX15 that causes a milder form of Cousin syndrome. Our patient presented with mild iliac and scapula hypoplasia, bilateral humeroradial dislocation, and a milder version of the distinctive facial appearance. We speculate that the biallelic missense variant in our patient either allows for some residual activity or affects some functions of the protein more than others. This finding expands the clinical spectrum of TBX15-related conditions by adding a milder phenotype caused by a homozygous missense variant.