Clinical Manifestations and Outcomes of 20 Korean Hypochondroplasia Patients with the FGFR3 N540K variant

Exp Clin Endocrinol Diabetes. 2023 Mar;131(3):123-131. doi: 10.1055/a-1988-9734. Epub 2022 Nov 28.


Background: Hypochondroplasia is a skeletal dysplasia caused by activating pathologic variants of FGFR3. The N540K variant accounts for 60-70% of reported cases and is associated with severe manifestations. Here, we analyze the clinical manifestations and outcomes of Korean patients with hypochondroplasia harboring the FGFR3 N540K variant.

Methods: Medical records of 20 unrelated patients with genetically confirmed N540K-related hypochondroplasia were retrospectively reviewed. All individuals were diagnosed with hypochondroplasia by Sanger sequencing for FGFR3, or target-panel sequencing for skeletal dysplasia. The effectiveness of growth hormone therapy was analyzed in 16 patients treated with growth hormones.

Results: Among 20 patients (7 men, 13 women), the mean age at first visit was 3.5±1.0 years, and the mean follow-up duration was 6.8±0.6 years. The patients presented with a short stature and/or short limbs. Genu varum, macrocephaly, and developmental delay were observed in 11 (55.0%), 9 (45.0%), and 5 (25.0%) patients, respectively. Of the 12 patients who underwent neuroimaging, five (41.7%) showed abnormal findings (one required operation for obstructive hydrocephalus). Among 16 growth-hormone-treated patients (two were growth-hormone deficient), the increase in height standard deviation scores was significant after a mean 5.4±0.7 years of treatment (+0.6 and+1.8 using growth references for healthy controls and achondroplasia children, respectively). Four patients underwent surgical limb lengthening at a mean age of 8.8±3.3 years.

Conclusions: Neurodevelopmental abnormalities are frequently observed in patients with N540K-related hypochondroplasia. Close monitoring of skeletal manifestations and neurodevelopmental status is necessary for hypochondroplasia.

MeSH terms

  • Achondroplasia* / diagnosis
  • Achondroplasia* / drug therapy
  • Achondroplasia* / genetics
  • Child
  • Child, Preschool
  • Female
  • Human Growth Hormone*
  • Humans
  • Male
  • Mutation
  • Osteochondrodysplasias* / genetics
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics
  • Republic of Korea
  • Retrospective Studies


  • Human Growth Hormone
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3

Supplementary concepts

  • Hypochondroplasia