{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:46:24Z","timestamp":1791996384340,"version":"4.4.0"},"reference-count":24,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Res Paediatr"],"abstract":"<jats:p>Introduction: Hypochondroplasia (HCH) is a mild and often under-recognized skeletal dysplasia caused by heterozygous variants in FGFR3. It is characterized by disproportionate short stature and subtle radiographic findings, which may delay diagnosis. This study aimed to evaluate the clinical, radiological, and molecular characteristics of patients with HCH and related FGFR3 variant carriers. Methods: In this retrospective, single-center study, we reviewed 23 individuals from 14 families with heterozygous FGFR3 variants confirmed by clinical exome sequencing and\/or Sanger sequencing. Clinical, anthropometric, radiological, endocrine, and molecular data were analyzed. Variants were classified according to ACMG\/AMP criteria and interpreted with respect to their established relevance to the skeletal phenotype. Results: The cohort comprised 13 females and 10 males, with ages ranging from 1.95 to 50.4 years. Eighteen patients carried pathogenic or likely pathogenic variants with established skeletal relevance, whereas five carried variants of uncertain significance or variants with uncertain skeletal relevance. Disproportionate short stature was present in 59.1% and macrocephaly or relative macrocephaly in 40.9% of patients with available data. The most frequent radiological findings were increased lumbar lordosis and absent caudal widening of the lumbar interpedicular distance, followed by midfacial retrusion and scoliosis. Eight distinct FGFR3 variants were identified, most commonly p.(Asn540Ser) and p.(Asn540Lys). Patients with p.(Asn540Ser) showed a nonsignificant trend toward a milder phenotype than those with p.(Asn540Lys). Marked phenotypic variability was observed, including variable skeletal severity and craniosynostosis in 1 patient with p.(Asn540Lys). Although acanthosis nigricans has been associated with both p.(Lys650Thr) and p.(Glu768*) variants, its occurrence with p.(Glu768*) has not previously been described in the context of HCH; therefore, it was regarded as a variant-associated finding rather than a defining feature of HCH. Conclusion: This study expands the clinical and molecular spectrum of FGFR3-related HCH and underscores its genetic and phenotypic heterogeneity. Molecular characterization, together with careful distinction between variants with established skeletal relevance and those of uncertain significance, is essential for accurate diagnosis, clinical follow-up, and refinement of genotype-phenotype correlations.<\/jats:p>","DOI":"10.1159\/hrp\/adaag025","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:49:28Z","timestamp":1788954568000},"page":"1-1","source":"Crossref","is-referenced-by-count":0,"title":["Refining the Hypochondroplasia Phenotypic Continuum: Genetic, Endocrine, and Radiological Findings in 23 Patients"],"prefix":"10.1159","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9316-9910","authenticated-orcid":false,"given":"Abdulkerim","family":"Kolkiran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melike 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