Endocrine Abstracts

JOINT1839

Introduction: Hypochondroplasia (HCH), caused by pathogenic variants in FGFR3, presents significant diagnostic challenges due to its phenotypic variability and subtle radiological findings. MRI findings, particularly hippocampal malrotation and abnormalities of the transverse temporal sulcus, have been identified as being more prevalent in conditions secondary to pathogenic variations in FGFR3, such as HCH. Hippocampal malrotation has a reported prevalence of 15-20% in the general population, and is more frequently observed in the left hemisphere (20%) than in the right (9%). We hypothesized that hippocampal malrotation and transverse temporal sulcus abnormalities are more common in HCH compared to the general population, and therefore could be helpful in the diagnostic workup of children with short stature.

Methods: A cohort of 29 children with genetically confirmed HCH was included in this study, involving Great Ormond Street Hospital and Evelina London Children’s Hospital. Their high-resolution brain MRIs were anonymised and randomized with a cohort of 29 age-matched controls with short stature and suspected growth hormone deficiency. Two neuroradiologists (of 15 and 5 years’ experience) were asked to separately assess the MRIs for hippocampal malrotation and transverse temporal sulcus abnormalities for each hemisphere. Significant differences from the age-matched cohort were calculated, and sensitivity and specificity in identifying HCH were evaluated. Inter-rater reliability was assessed using Cohen’s kappa.

Results: The findings for each hemisphere in the HCH and age-matched control cohort are presented in the table. Overall, transverse temporal sulcus abnormalities showed the highest sensitivity and specificity in identifying children with HCH. Chi-squared test showed a significant association between hippocampal malrotation, transverse temporal sulcus abnormalities and HCH. Excellent inter-rater reliability was observed in evaluating hippocampal malrotation (Cohen’s kappa: 0.83 right, 0.76 left) and transverse temporal sulcus abnormalities (Cohen’s kappa: 0.93 right, 0.96 left).

Conclusions: Our novel findings suggest that transverse temporal sulcus abnormalities and hippocampal malrotation are highly sensitive and specific biomarkers and may be important in the diagnosis HCH, especially in cases where skeletal findings are ambiguous. Future studies should explore whether these findings could also be useful for prenatal diagnosis through foetal imaging.