Diagnostic guide to hypochondroplasia.

Abstract

Hypochondroplasia is a skeletal dysplasia characterized by disproportional short stature with rhizomelic limb shortening, caused by pathogenic variants of FGFR3, most frequently the p.Asn540Lys variant. However, affected individuals harbor a wide variety of pathogenic variants, accounting for the broad phenotypic spectrum of the disorder. Despite being closely related to achondroplasia, hypochondroplasia is a milder condition that was previously believed to be recognizable only in childhood, but not in infancy. However, the widespread use of prenatal ultrasonography and frequent diagnosis of fetal limb shortening have increased the number of hypochondroplastic neonates identified, thereby clarifying the early radiographic findings of the disorder. Radiological diagnosis of hypochondroplasia in children carrying the p.Asn540Lys variant is currently feasible in the neonatal period or even prenatally, using three-dimensional CT. Conversely, some individuals have a mild phenotype with minimal skeletal abnormalities, which hampers the differential diagnosis of hypochondroplasia and constitutional short stature. For a definitive diagnosis, genetic testing for FGFR3 is recommended. This diagnostic guide aims to assist in the early recognition of hypochondroplasia and to facilitate the management of affected children.