Achondroplasia

Most common skeletal dysplasia (genetic dwarfism) caused by an FGFR3 gene mutation (gain-of-function) that inhibits endochondral bone growth, leading to disproportionate short stature (short limbs, near-normal torso).

• Prototypical dwarfism: relatively common (~1 in 20–30k births) and frequently tested. Early recognition is crucial to manage life-threatening complications (e.g., brainstem compression in infancy) and to counsel families on genetics.

• Prenatal: ultrasound in mid-pregnancy often shows shortened long bones (especially femur). Newborns have obvious disproportionate short stature (rhizomelic limb shortening with normal trunk length), macrocephaly with frontal bossing, midface hypoplasia, and sometimes a trident hand (gap between third and fourth fingers).
• Infancy/Childhood: Hypotonia in infancy leads to delayed motor milestones, but cognitive development is normal. As children grow, they develop exaggerated lumbar lordosis and genu varum (bowed legs). Recurrent otitis media is common (eustachian tube dysfunction from skull base abnormalities). Head growth must be monitored (risk of hydrocephalus).
• Adulthood: Short stature (~4 feet average) with near-normal life span. Spinal stenosis (narrow spinal canal) is a frequent source of chronic back & leg pain and neurologic symptoms in adulthood. Obesity is prevalent. Intelligence is normal.

1. If prenatal ultrasound suggests a skeletal dysplasia (short limbs), consider FGFR3 genetic testing (via amniocentesis or CVS) to confirm achondroplasia and distinguish from lethal forms (e.g., thanatophoric dysplasia).
2. At birth, perform a thorough neonatal exam. Look for the hallmark features of achondroplasia and obtain baseline neuroimaging (CT/MRI) of the brain and craniocervical junction to check for foramen magnum stenosis or hydrocephalus.
3. Anticipate and address complications: foramen magnum decompression surgery if there are signs of brainstem compression; ventriculoperitoneal shunt if hydrocephalus develops; prompt treatment of ear infections with tympanostomy tubes to prevent hearing loss; adenotonsillectomy or CPAP for obstructive sleep apnea.
4. Provide genetic counseling and support: Explain that achondroplasia is autosomal dominant with ~80% due to a new mutation (often associated with advanced paternal age). If one parent is affected, each child has a 50% chance; if both parents have achondroplasia, there is a 25% chance of a lethal homozygous form. Emphasize early intervention and monitoring rather than expecting normal growth (standard growth hormone therapy is ineffective).

1. No cure for short stature in achondroplasia. (Standard growth hormone therapy has minimal effect.) A new drug, vosoritide (C-type natriuretic peptide analog), can modestly increase growth velocity in children with open growth plates.
2. Focus on supportive care and complication management: weight control and physical therapy to improve mobility; neurosurgical interventions (foramen magnum decompression, spinal stenosis surgery, shunt placement) when needed; ENT interventions (ear tubes for chronic otitis media, adenotonsillectomy for sleep apnea) to improve quality of life.
3. Provide psychosocial support and accommodations: ensure appropriate developmental support, use adaptive devices and home modifications for short stature, and offer family counseling (emphasize normal intelligence and a full life expectancy with proper care).

• High-yield association: Advanced paternal age — older fathers have higher odds of new FGFR3 mutations causing achondroplasia.
• Remember the mechanism: FGFR3 mutation is a gain-of-function that keeps the growth-limiting signal stuck in the 'on' position (FGFR3 acts like a constantly active brake on bone growth).

• Episodes of apnea, significant hypotonia, or neck pain in an achondroplastic infant → red flag for craniocervical junction compression (foramen magnum stenosis) requiring urgent neurosurgical evaluation.
• Rapidly enlarging head circumference or bulging fontanelle in infancy → concerning for developing hydrocephalus (brain imaging and neurosurgical consult for possible shunt).
• Sudden onset of leg weakness, gait change, or bladder/bowel dysfunction in an older child or adult → evaluate immediately for spinal cord compression due to severe spinal stenosis.

1. Short femur length on prenatal ultrasound → suspect skeletal dysplasia; offer FGFR3 genetic testing (prenatal or postnatal) to confirm achondroplasia vs other forms.
2. Newborn with disproportionate short stature → perform diagnostic evaluation (clinical exam ± genetic test) to confirm achondroplasia; begin monitoring head size and neurologic status.
3. Infancy: baseline neuroimaging (head and neck) to assess foramen magnum size and ventricles; schedule regular exams for developmental milestones, breathing (signs of apnea), and hearing (due to frequent otitis).
4. Childhood: use achondroplasia-specific growth charts for height/head; at each visit, check for developing kyphosis or leg bowing, and perform neuro exams (watch for any cord compression signs).
5. Lifelong management: coordinate care with specialists (neurosurgery, orthopedics, ENT, etc.); intervene early when complications arise (decompression, shunting, etc.) to prevent permanent sequelae.

• Newborn with disproportionate short limbs, a large head with frontal bossing and midface hypoplasia (often noted in a baby of an older father) → Achondroplasia (FGFR3 mutation).
• Achondroplastic adult (~4 ft tall) with new-onset leg numbness and urinary incontinence → suspect spinal cord compression from lumbar spinal stenosis (common complication).