Hypochondroplasia is an autosomal dominant skeletal dysplasia sharing many phenotypic features, such as apparent rhizomelia, limitation of elbow extension, tibial bowing, exaggerated lumbar lordosis, metaphyseal flaring, shortening of the pedicles, narrowing of the lumbar interpediculate distance, squared ilia, shortened femoral necks, brachydactyly, macrocephaly, and distinctive facial features, with achondroplasia. However, in hypochondroplasia these features tend to be milder, and some are often subtle or absent. For these reasons, the diagnosis is frequently not made until later in childhood, when growth delay is first noted.
Hypochondroplasia is caused by mutation in the gene for fibroblast growth factor receptor-3 mapped to chromosome 4p16.3. FGFR3 is a member of the tyrosine kinase receptor family. The four known members (FGFR1-4) of this family play important roles in the regulation of proliferation, differentiation, and angiogenesis, as well as other processes involved in growth and development. Structurally, they comprise three extracellular immunoglobulin-like domains (Ig-like domains I-III), one transmembrane domain, and a split intracellular tyrosine kinase domain. FGFR3 is expressed during skeletal growth and endochondral ossification. FGFR3 seems to have a specific role as negative regulator of bone growth, and the known FGFR3 mutations result in a ligand independent activation of the receptor.