Achondroplasia

What is it?

Cause

• Caused by a mutation in the FGFR3 gene (Fibroblast Growth Factor Receptor 3)
• Over 99% of cases are caused by a single change at position c.1138 in the gene (p.Gly380Arg substitution)
• This mutation is a gain-of-function change - it keeps FGFR3 permanently "switched on," which abnormally inhibits cartilage cell (chondrocyte) growth in the long bones
• About 80% of cases are new (de novo) mutations - meaning neither parent has the condition
• The remaining 20% inherit it from an affected parent (autosomal dominant inheritance)
• Incidence: 1 in 15,000 to 1 in 40,000 live births

What happens to the head and body?

• At birth, body length, weight, and head size may look nearly normal
• Within the first few months, the body length falls below normal growth curves...
• ...while head circumference shoots up above the 95th percentile
• The arms and legs (especially the upper portions - rhizomelic shortening) remain disproportionately short
• The trunk is relatively long compared to the limbs
• Intelligence is completely normal in most cases

Key features

Complications to watch for

• Foramen magnum stenosis - the opening at the base of the skull is too narrow, which can compress the brainstem and cause breathing problems or even sudden death in up to 5% in the first year of life
• Sleep apnea (both obstructive and central types)
• Recurrent ear infections and hearing loss
• Spinal stenosis in adulthood
• Bowed legs (genu varum)
• Obesity

Treatment

• MRI scans to check for brainstem compression in infancy
• Surgical decompression if needed
• Monitoring for hearing, sleep apnea, and spine problems
• Vosoritide (a newer FDA-approved medication) can increase growth in children with achondroplasia
• Growth hormone therapy and surgical limb lengthening are options but remain debated
• Avoiding high-risk activities (contact sports, trampolines, diving) that could injure the neck