Pathogenesis and potential therapeutic targets of trichorhinophalangeal syndrome; lessons obtained from animal studies

Trichorhinophalangeal syndrome (TRPS) is a rare genetic disease inherited in an autosomal dominant manner. It occurs in 1 in 100,000 people globally and is caused by several types of mutations of the TRPS1 gene. Since the first human patient was reported in 1966, typical and atypical pathologies, disease courses, and treatment case presentations have been reported. TRPS is characterized by sparse slow-growing fine hair, a bulbous nose with tented nares, and brachydactyly with cone-shaped epiphyses on the hands and feet. Growth retardation and hip dysplasia are also frequently observed, suggesting that hair and skeletal phenotypes are the major pathologies of TRPS. Several animal models have been established and studied intensively to address this rare disease. However, comprehensive treatment strategies for TRPS have not been established. In this review, we summarize TRPS pathologies and the characteristics of TRPS1 as an atypical GATA-type transcription factor. We review rodent strains that have contributed to our understanding of the in vivo roles of Trps1 and discuss their validity as animal models of TRPS. We also summarize diseases that demonstrate pathologies similar to TRPS and findings in their animal models.