Endocrine Abstracts

JOINT224

Background/Objectives: Tricho-rhino-phalangeal syndrome, type I (TRPS I, OMIM#190350) is a rare autosomal dominant disorder characterized by distinctive craniofacial features, skeletal abnormality, and ectodermal dysplasia. Due to variable expressivity, TRPS I often remains undiagnosed, leading to unclear prevalence and a lack of large-scale cohort studies. This study aims to delineate the clinical features and genotypes of TRPS I patients in Korea.

Methods: We retrospectively reviewed the medical records of 20 genetically confirmed TRPS I patients (8 males, 12 females) from 20 families. Data collected included demographic information, clinical profiles (growth, craniofacial features, ectodermal dysplasia, skeletal abnormalities), radiologic findings, and treatment history. Genetic diagnoses were confirmed using Sanger sequencing, MLPA, qPCR, or gene panel sequencing.

Results: The median age at diagnosis is 9.0 years old (range: 20 months to 35.1 years). Short stature (35%) was the most common presenting symptom, followed by hypotrichosis (20%) and finger deformity (15%). Almost all patients (95%) had heights below the 50th percentile, with a median height of -1.25 SDS at diagnosis. Four patients (21%) had heights below -2.0 SDS. After 12 years of age, height SDS significantly decreased, accompanied by accelerated bone age, suggesting impaired pubertal growth spurt. Patients aged 12 years and older had significantly lower height SDS than those under 12 (P =0.016). Clinical features included sparse hair (100%), sparse eyebrows (83%), and a pear-shaped nose (100%). Skeletal surveys showed cone-shaped epiphyses in all patients. Four patients (20%) had skeletal abnormalities, including hip dysplasia, with two undergoing hip surgery and one requiring femur osteotomy. Fourteen patients (70%) have been treated with Minoxidil for hypotrichosis, with 50% showing improvement. Genetic analysis revealed diverse pathogenic variants in TRPS1, with 4 (20%) patients having exonic deletions. All 16 sequence variants were private. Variants were distributed across exons 3 to 7, with 9 (45%) being novel. Thirteen (65%) patients had frameshift or nonsense variant. For hand deformities, the exon 6 missense variant was associated with severe hand deformities, while other genotypes exhibited variable severity.

Conclusion: TRPS I can present with short stature, alopecia, and early-onset skeletal dysplasia in pediatric patients, with impaired pubertal growth spurt and accelerated bone age. There were no mutational hotspots, and hand deformities were most severe in patients with exon 6 missense variants. Copy number variation analysis is essential for identifying the genetic etiology in patients without sequence alterations.