Two cases of Legg–Perthes and intellectual disability in Tricho–Rhino–Phalangeal syndrome type 1 associated with novel TRPS1 TRPS1 mutations

摘要

Tricho–Rhino–Phalangeal syndrome is a rare autosomal dominant genetic disorder caused by mutations in the TRPS1 gene. This malformation syndrome is characterized by distinctive craniofacial features including sparse scalp hair, bulbous tip of the nose, long flat philtrum, thin upper vermilion border, and protruding ears. Skeletal abnormalities include cone‐shaped epiphyses at the phalanges, hip malformations, and short stature. In this report, we describe two patients with the physical manifestations and genotype of TRPS type I but with learning/intellectual disability not typically described as part of the syndrome. The first patient has a novel heterozygous two‐base‐pair deletion of nucleotides at 3198‐3199 (c.3198‐3199delAT) in the TRPS1 gene causing a translational frameshift and subsequent alternate stop codon. The second patient has a 3.08 million base‐pair interstitial deletion at 8q23.3 (113,735,487–116,818,578), which includes the TRPS1 gene and CSMD3 . Our patients have characteristic craniofacial features, Legg–Perthes syndrome, various skeletal abnormalities including cone shaped epiphyses, anxiety (first patient), and intellectual disability, presenting unusual phenotypes that add to the clinical spectrum of the disease.