The Clinical and Molecular Spectrum of Trichorhinophalangeal Syndrome Types I and II in a Turkish Cohort Involving 22 Patients

Güneş N., Usluer E., Ülker A. Y., ULUDAĞ ALKAYA D., Sunamak E. Ç., Eyüpoğlu F. C., ...More

Turkish Archives of Pediatrics, vol.58, no.1, pp.98-104, 2023 (Scopus) identifier identifier

  • Publication Type: Article / Article
  • Volume: 58 Issue: 1
  • Publication Date: 2023
  • Doi Number: 10.5152/turkarchpediatr.2022.22223
  • Journal Name: Turkish Archives of Pediatrics
  • Journal Indexes: Scopus, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.98-104
  • Keywords: brachydactyly, cone-shaped epiphyses, exostosis, Trichorhinophalangeal syndrome, TRPS1
  • Istanbul University Affiliated: Yes


© 2023, AVES. All rights reserved.Objective: Trichorhinophalangeal syndrome is a rare autosomal dominant disorder character-ized by distinctive craniofacial and skeletal abnormalities. This study aimed to delineate the trichorhinophalangeal syndrome phenotype and to compare the clinical and molecular findings between trichorhinophalangeal syndrome types I and II. Materials and Methods: A total of 22 trichorhinophalangeal syndrome patients aged 0.9-45 years from 17 families were enrolled. Nineteen patients were diagnosed with trichorhin ophalangeal syndrome I and 3 with trichorhinophalangeal syndrome II. Genetic analyses were made by TRPS1 sequencing and/or chromosomal microarray analyses. Results: A novel frameshift variant (c.531_532del), a known missense variant, and whole-gene deletions were the pathogenic TRPS1 variants detected in trichorhinophalangeal syndrome I. Three trichorhinophalangeal syndrome II patients had large deletions with variable breakpoints involving the TRPS1-EXT1 interval. All patients had the typical craniofacial findings of trichorhinophalangeal syndrome such as a pear-shaped nose, long philtrum, and thin upper lip, as well as cone-shaped epiphyses. Sparse hair and eyebrows (20/22), short metacarpals and metatarsals (20/22), and small hands (19/22) were common. While craniofacial and limb abnormalities were similar in trichorhinophalangeal syndrome I and II, 3 of 19 trichorhinophal angeal syndrome I patients had mild, and 2 of 3 trichorhinophalangeal syndrome II patients had severe intellectual disability. Three trichorhinophalangeal syndrome II patients including the patient with the EXT1 deletion beginning from exon 2 had exostoses. In trichorhinophal angeal syndrome II, although microdeletion sizes and facial or skeletal features were not cor-related, patients with larger deletions had severe intellectual disability. Conclusion: This study has expanded the existing knowledge on the phenotype–genotype spectrum in trichorhinophalangeal syndrome. We suggest including the EXT1 gene partially in the minimal critical region for trichorhinophalangeal syndrome II.