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Updated: Dec 6, 2025
Assessment of Child Anthropometry in a Large Epidemiologic Study
Published on: February 2, 2017
Earlier detection of hypochondroplasia: A large single-center UK case series and systematic review
Ataf H Sabir1,2,3, Jameela Sheikh3, Ananya Singh3
1Department of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Insights
Hypochondroplasia (HCH), a rare skeletal dysplasia, is increasingly detected antenatally due to improved awareness and imaging. Early detection is crucial as targeted therapies for FGFR3 conditions are emerging.
Area of Science:
- Genetics and Developmental Biology
- Skeletal Dysplasias
- Medical Imaging
Background:
- Hypochondroplasia (HCH) is a rare autosomal dominant skeletal dysplasia caused by FGFR3 mutations, typically presenting with disproportionate short stature.
- Classical HCH presentation often occurs in toddlers or school-aged children, with milder forms frequently missed in infancy.
Purpose of the Study:
- To investigate the rate of antenatal detection of HCH in a UK cohort.
- To describe antenatal findings and patient data for HCH cases detected prenatally.
- To review the literature on antenatally suspected HCH.
Main Methods:
- Analysis of a single-center UK cohort of 31 HCH patients with confirmed molecular diagnosis by age 3.
- Inclusion of 13 patients with antenatal ultrasound findings (short long bones or large head size).
- Systematic literature review of PUBMED and MEDLINE for antenatally suspected HCH cases (2004-2019).
Main Results:
- 41.9% (13/31) of the UK cohort had antenatal HCH detection.
- Consistent antenatal markers included reduced femur length, reduced humeral length, increased biparietal diameter, and increased head circumference.
- 15 literature cases of antenatally suspected HCH with molecular confirmation were identified.
Conclusions:
- HCH detection is increasing in infancy and antenatally, contrary to previous understanding.
- Increased HCH awareness, advanced imaging, and accessible molecular testing contribute to earlier diagnosis.
- Consideration of HCH outside its classical presentation period is warranted, especially with emerging FGFR3-targeted therapies.
Abstract:
Hypochondroplasia (HCH) is a rare autosomal dominant skeletal dysplasia condition caused by FGFR3 mutations leading to disproportionate short stature. Classically HCH presents in toddlers or school-age children, as limb-to-trunk disproportion and is often mild and easily overlooked during infancy. We report experiences from a single-center UK HCH-cohort of 31 patients, the rate of antenatal HCH detection in our cohort (13/31, 41.9%) and describe relevant case-data for this subset of 13 patients. Inclusion criteria were patients with confirmed molecular HCH diagnosis (by age 3 years) and presenting with short long-bones or large head size on antenatal ultrasound scan. We then conducted a systematic literature review using PUBMED and MEDLINE, analyzing patients with HCH and related antenatal findings. Antenatally suspected (with subsequent molecular confirmation) HCH has been reported 15 times in the literature (2004-2019). Key markers (consistent in both groups) included reduced; femur length, humeral length and increased; biparietal diameter and head circumference. HCH is increasingly detected both antenatally and in infancy, contrary to previous descriptions. This is likely due to greater HCH awareness, improved imaging, and easier molecular testing. Thus, one should consider HCH outside the classical presenting period. Studying the natural history of younger patients with HCH is important with the advent of several targeted FGFR3 therapies currently in trials for Achondroplasia, that may soon be trialed in HCH.
