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

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 manifesta-tions and outcomes of Korean patients with hypochondroplasia harboring the FGFR3 N540K variant.Methods Medical records of 20 unrelated patients with ge- netically 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 pa- tients who underwent neuroimaging, five (41.7 %) showed abnormal findings (one required operation for obstructive hy- drocephalus). 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 fre-quently observed in patients with N540K-related hypochon-droplasia. Close monitoring of skeletal manifestations and neurodevelopmental status is necessary for hypochondropla-sia.

Automated summary

This study analyzed the clinical manifestations and outcomes of Korean patients with hypochondroplasia harboring the FGFR3 N540K variant. The results showed that these patients often presented with short stature, short limbs, genu varum, hydrocephalus, and developmental delay. After growth hormone therapy, there was a significant increase in height. These findings highlight the importance of monitoring skeletal manifestations and neurodevelopmental status in patients with hypochondroplasia.