Trichorhinophalangeal Syndrome Type I: A Patient with Two Novel and Different Mutations in the TRPS1 Gene

Abstract

Background. Trichorhinophalangeal syndrome (TRPS) is an autosomal dominant skeletal dysplasia caused by defects involving the TRPS1 gene. Three types (TRPSs I, II, and III) have been described, exhibiting the common triad of hair, craniofacial, and skeletal abnormalities. TRPS II includes the additional characteristics of mental retardation and multiple exostoses. Case Report. We describe a sporadic case of TRPS type I in a child with two novel nonsense pathogenic mutations in the TRPS1 gene, both in heterozygosity—c.1198C>T (p. Gln400X) and c.2086C>T (p.Arg696X). None of these mutations were found in her parents. Clinical presentation included typical hair and facial features, as well as slight skeletal abnormalities. Discussion. There is a wide variability in clinical expression of TRPS I. Manifestations of the disease can be subtle, yet skeletal anomalies imply that TRPS I is more than an esthetic problem. Clinical and genetic diagnosis allows adequate followup and timely therapeutic procedures. When a single mutation was sufficient for the onset of the disease, our patient presented two different ones.

Crooked fingers and sparse hair: an interesting case of trichorhinophalangeal syndrome type 1

“…TRPS is a rare skeletal dysplasia of autosomal-dominant inheritance 1 2. It is caused by defects in the TRPS1 gene located on chromosome 8, which encodes a transcriptional repressor involved in hair development and chondrocyte modulation 1.…”

“…It is caused by defects in the TRPS1 gene located on chromosome 8, which encodes a transcriptional repressor involved in hair development and chondrocyte modulation 1. Three types of TRPS have been described: TRPS type I, TRPS type II and TRPS type III.…”

“…Three types of TRPS have been described: TRPS type I, TRPS type II and TRPS type III. In contrast to TRPS type I, patients with TRPS type II suffer from mental retardation and develop multiple exostoses 1. TRPS type III is the rarest type, with patients having normal intelligence and severe shortening of all phalanges and metacarpals 1…”

“…Characteristic clinical features include trichological abnormalities such as sparse slow-growing hair 1 2. Sparseness is caused by thinning of individual hair follicles and can affect the eyebrows, eyelashes, beard, axillary and pubic hair 1. Facial abnormalities include bulbous pear-shaped nose, long and flat philtrum and high frontal hairline 1.…”

Trichorhinophalangeal Syndrome

“…It presents diffuse rarefaction of the hair, with a pattern of noncicatricial alopecia, fine and short hair, rarefaction of the distal third of the eyebrow, bulbous nose and enlargement of the nasolabial filter, fine upper lip, micrognathism, short stature, brachydactyly, curved feet and shortening of some metacarpals shaped nose, elongated filter, thin upper lip and bone alterations, particularly cone-shaped epiphyses in the fingers (distinctive feature of the syndrome) [1][2][3][4][5], TRPS type II, which is associated with microcephaly and mental retardation, cartilaginous exostoses and others more severe osteoarticular manifestations; and TRPS type III, a type I proximal variant, which is phenotypically differentiated by the accentuation of shortening of the phalanges, metacarpals and metatarsals, and of short stature [2]. Other phenotypic alterations may be associated and are described in Table 1.…”