Hypochondroplasia is a clinical entity characterized by a short stature and a range of skeletal malformations, occurring due to mutations in the fibroblast growth factor 3 gene, one of the key negative regulators of bone growth and development. A clinical suspicion must exist when typical signs and symptoms are observed, and radiologic, as well as genetic studies, are used to confirm the diagnosis.
The clinical presentation of patients with hypochondroplasia (HCH), unlike other disorders involving the fibroblast growth factor 3 (FGF3) gene, such as achondroplasia, may be insidious, and rarely start during infancy and childhood  . The cardinal manifestation of HCH is a short stature, ranging from severe dwarfism to only mild reductions  . Shortening of the lower limbs, genu varum (bowing of the legs), an increased sitting height to standing height ratio, and a reduced growth rate is most frequently detected at the end of puberty when boys and girls fail to reach adequate height based on their previous growth rates . Numerous features can accompany short stature - macrocephaly, a prominent forehead, brachydactyly involving both the hands and the feet, lumbar lordosis, and a limited range of joint motion (elbows are commonly affected) are frequent manifestations, with marked variations in terms of severity from patient to patient  . Many individuals, however, remain undiagnosed for a significant period of time or are misdiagnosed as idiopathic short stature  . Moreover, insulin resistance and the appearance of acanthosis nigricans, a papillomatous pigmented hyperkeratosis of the skin appearing on the flexures of the neck in most cases, which is strongly associated with FGF3-related disorders due to its role in pancreatic proliferation, is infrequently present in HCH patients  . In some individuals, intellectual impairment may be noted.
Physicians can make a presumptive diagnosis of HCH only with a meticulously performed physical examination, as very subtle or mild skeletal changes are observed in the majority of patients. Assessment of growth rate, examination of the extremities, establishing body proportions and determination of joint mobility are mandatory parts of the physical examination. Having in mind that HCH is transferred through an autosomal dominant pattern of inheritance, patient history could potentially reveal similar findings in one of the parents, but many mutations arise de novo (sporadically) , and for this reason, the diagnosis should not be excluded in the absence of a positive family history. If reduced growth or a short stature is revealed, radiological studies should be employed . Plain radiography of the spine, arms, and legs may reveal several key features - flared metaphyses, short femoral neck, square ilia and narrow interpedicular spaces . A more concrete diagnosis can be made based on clinical and radiologic findings, but to confirm HCH as the underlying cause, genetic studies are the final step in the workup. Molecular analysis of FGF3 and detection of mutations involving this gene is detrimental .