Achondroplasia

Achondroplasia is the most common form of disproportionate short stature in humans. It results from a gain-of-function mutation in the FGFR3 gene, which encodes a receptor that regulates endochondral bone growth. Most cases occur as new (de novo) mutations, but the condition can be inherited in an autosomal dominant pattern. Homozygous achondroplasia, having two mutant alleles, is rare and typically lethal in infancy; heterozygous achondroplasia is the usual presentation.

Clinical features include short limbs with rhizomelic shortening, a relatively normal trunk length, and a large head with frontal bossing. Midface hypoplasia, lumbar lordosis, and a prominent forehead are common. Hands may show a characteristic trident configuration. Cognitive development is typically normal, though motor milestones may be delayed due to limb proportions.

Complications arise from skeletal abnormalities and neurological risk, including cervicomedullary compression, spinal stenosis, obstructive sleep apnea, recurrent ear infections, and foramen magnum stenosis. Growth is slower than in unaffected children, leading to final adult stature averaging around 120 to 130 cm.

Diagnosis is based on clinical features and radiographic findings, with confirmation by genetic testing identifying a FGFR3 mutation. The most common mutation is G380R. Prenatal diagnosis is possible if a risk is known, through ultrasound and targeted genetic testing.

Management requires a multidisciplinary approach, focusing on monitoring growth and development, treating orthopedic and neurological complications, ensuring adequate sleep and hearing, physical therapy, and regular follow-up. There is no cure; treatment is supportive and aimed at maximizing quality of life.