Achondroplasia

Excerpt

Achondroplasia is a rare genetic disorder recognized as the most common primary skeletal dysplasia in humans. This form of dysplasia accounts for greater than 90% of cases of disproportionate short stature, also known as dwarfism. The term “achondroplasia” was first used in 1878 to distinguish it from rickets, one of many other abnormal conditions of bone growth.

Achondroplasia means “without cartilage formation,” and it is categorized as a physeal (growth plate) dysplasia. The condition’s causative mutation of the transmembrane portion of fibroblast growth factor receptor 3 (FGFR3) was discovered in 1995. It follows an autosomal dominant pattern of inheritance with 100% penetrance. Over 80% of cases arise from a spontaneous mutation, and advanced paternal age is a known risk factor. The phenotype is distinct from other skeletal dysplasias and can be identified on prenatal ultrasonography and by newborn examination.

Affected individuals usually present average intelligence and have an estimated mean lifespan of 61 years, about ten years less than the general population. Physical phenotypic features include large head size (macrocephaly) with frontal bossing, midface hypoplasia, rhizomelic shortening of the extremities, short fingers (brachydactyly) with trident configuration of the hand, and bowed legs (genu varum).

Achondroplasia is associated with increased mortality in early childhood, otolaryngology problems later in childhood, and increased risk of obesity into adulthood. Affected individuals can also develop joint laxity, thoracolumbar kyphosis (TLK), and spinal stenosis that may progress and contribute to morbidity as an adult.