Novel Frameshift Mutation in TRPS1 in a Ukrainian Patient with Trichorhinophalangeal Syndrome Type I.

Trichorhinophalangeal syndrome (TRPS) type I is a rare autosomal dominant disorder, caused by mutations in the TRPS1 gene. It is characterized by slowly growing hair, craniofacial manifestations and orthopedic abnormalities. We present a 17-year-old female of Ukrainian origin who presented to the hair clinic with the complaint of hair loss. Further examination revealed the presence of craniofacial features characteristic for TRPS type I. Sequence analysis of the TRPS1 gene revealed a novel c. 2396_2397 insG frameshift mutation in exon 5, leading to a premature stop at codon 800. This case underlines the importance of the hair phenotype to the diagnosis of this syndrome and emphasizes the fact that when encountered with a severe alopecia in young age, the possibility of a congenital hair disease should always be borne in mind.

INTRODUCTION

Trichorhinophalangeal syndrome (TRPS) type I (TRPSI, Online Mendelian Inheritance in Man [OMIM# 190350]) is a rare autosomal dominant disorder, which was first described in 1956 by Klingmuller.[1] It is characterized by slowly growing hair, craniofacial manifestations and orthopedic abnormalities.[2] The culprit gene is TRPS1, localized on chromosome 8q24, which encodes a zinc finger transcriptional repressor involved in hair development and chondrocyte modulation.[3] Based on the severity of the clinical manifestations, two additional subtypes have been described: TRPS type II (OMIM# 150230) and TRPS type III (OMIM 190351).[4] TRPS type III is also caused by mutations in TRPS1, but the allelic correlation between TRPS type III and TRPS type I is still unknown.[5] We present a TRPS type I patient of Ukrainian origin with a novel TRPS1 mutation.

CASE REPORT

The present case report is about a 17-year-old female patient, born to a non-consanguineous family of a Ukrainian origin, who presented with short and sparse scalp hair, most pronounced in the temporal area [Figure 1a] and in a unique triangular shape in the mid occipital scalp [Figure 1b]. Additional findings included beaked nose with a long philtrum and an allergic crease [Figure 1c], widened proximal interphalangeal joints [Figure 1d], short toes [Figure 1e] and onycholysis of finger- and toenails. Sequence analysis of the TRPS1 gene revealed a novel c. 2396_2397 insG frameshift mutation in exon 5, leading to a premature stop at codon 800 [Figure 1f].

Figure 1

(a-e) Clinical manifestations of the patient, demonstrating hair loss, finger and toe malformation and facial deformities (f) Sequence analysis of TRPS1 showing the heterozygous mutation 2396_2397 insG

DISCUSSION

Here we describe a case of TRPS type I, who presented to our hair clinic with the complaint of hair loss. Nevertheless, detailed examination of facial features and joints uncovered the diagnosis of TRPS type I, emphasizing the importance of the hair specialist in diagnosing this syndrome. This case underlines the fact that whenever the dermatologist is encountered with a severe alopecia in young age, the possibility of a congenital hair disease should always be borne in mind. This is especially true in TRPS, where androgenetic alopecia type of hair loss has been described.[6]

Interestingly, the patient showed a unique pattern of scalp hair loss, manifesting as triangular loss of hair in the mid occipital scalp, which was previously described in this syndrome[7] and might have been overlooked in additional patients. Our patient was diagnosed in a relatively advanced age, suggesting that the prevalence of TRPS type I is probably still underestimated and should be considered by dermatologists when examining new patients.

To the best of our knowledge, the c. 2396_2397 insG frameshift mutation was not previously reported. Therefore, this report adds one more mutation to the growing list of mutations reported in this syndrome. Considering the fact that the correlation between genotype and phenotype of TRPSI is still obscure,[2] the report of additional mutations can enhance our knowledge on this complicated and severe genetic disease.