Clinical and genetic spectrum of trichorhinophalangeal syndrome type I/III in 20 children of Korean origin

Abstract

Background

Trichorhinophalangeal syndrome type I/III (TRPS I/III) is a rare autosomal dominant skeletal dysplasia caused by pathogenic variants of TRPS1. Although several European cohorts have been reported, data from East Asian populations remain limited and longitudinal growth patterns and treatment responses have not been systematically evaluated.

Methods

We conducted a retrospective single-center study of 20 unrelated children of Korean origin with molecularly confirmed TRPS I/III, between 2012 and 2024. The clinical, radiological, and genetic data were reviewed. Growth parameters were analyzed using Korean reference standards and genotype–phenotype correlations were explored. Treatment responses to recombinant human growth hormone (rhGH) and minoxidil were assessed descriptively.

Results

All the patients exhibited characteristic craniofacial features and cone-shaped epiphyses with variable skeletal involvement. Short stature (standard deviation score [SDS] of height < −2) was observed in 21% of patients. Bone age was delayed before 12 years of age but showed rapid advancement thereafter, accompanied by a decline in height SDS during adolescence (p = 0.017). Truncating variants were identified in 65% of patients, missense variants in exon 6 in 15%, and exonic deletions in 20%. Missense variants in exon 6 were consistently associated with severe brachydactyly, whereas the overall stature showed no clear correlation with genotype. Responses to rhGH and minoxidil treatments were variable.

Conclusions

TRPS I/III demonstrated substantial phenotypic heterogeneity and age-dependent growth dynamics in this Korean cohort. Severe distal limb involvement was associated with exon 6 missense variants, whereas growth impairment remained variable. Long-term follow-up and multidisciplinary management are essential to optimize clinical outcomes.