Achondroplasia

CHAPTER 72

Achondroplasia

Introduction/Etiology/Epidemiology

• Achondroplasia is the most common skeletal dysplasia, with an incidence of 1 in 30,000 live births.

• Mutations of fibroblast growth factor receptor 3 (FGFR3) on chromosome 4 result in the inhibition of chondrocyte growth and proliferation, with underdevelopment and shortening of bones formed by endochondral ossification. Articular cartilage is unaffected.

• Patients with achondroplasia display manifestations in the spine, upper and lower extremities, and face.

• Inheritance is autosomal dominant.

• More than 80% of cases are sporadic.

• Advanced paternal age (older than 35 years) is associated with sporadic mutations.

Signs and Symptoms

• The primary feature of achondroplasia is short stature, defined as a height at least 2 standard deviations (SD) below the population mean.

— Short stature is caused by rhizomelic (proximal extremity) shortening—the humerus and femur are affected more than the forearm and tibia. Trunk length is in the lower range of normal.

— Patient length on average is −1.5 SD at birth, −4.4 SD at 1 year, and −5.0 SD at 2 years.

— The mean final adult height for those with achondroplasia is 6 to 7 SD below normal; the overall mean adult height for patients with achondroplasia is 52 inches (range, 46–57 inches) in men and 49 inches (range, 44–54 inches) in women.

• There may be frontal bossing and midface hypoplasia.

• During infancy, patients may have foramen magnum stenosis.

— Stenosis may present with sleep apnea, excessive snoring, signs of chronic brainstem compression (ie, lower cranial nerve dysfunction, swallowing difficulty, hyperreflexia, hypotonia, weakness, developmental delay, and clonus), or death

• Most neonates develop thoracolumbar kyphosis as sitting begins.

— When sitting begins, these newborns slump forward because of their large heads and poor trunk control.

— Repeated slumping can increase the kyphosis and result in anterior wedging of the vertebral bodies.

— Examination reveals a gibbus or prominence of the thoracolumbar junction when the neonate is in the sitting position. An infant with a “bump on their back” from a kyphotic thoracolumbar spine may prompt further evaluation, including radiographic and genetic evaluation, because many patients with achondroplasia or other skeletal dysplasias may present this way.

— Thoracolumbar kyphosis in patients with achondroplasia is defined by the presence of more than 20 degrees of kyphosis at the thoracolumbar junction.

— Most kyphoses resolve within 1 year after walking begins.

— Persistent thoracolumbar kyphosis occurs in 30% of patients and may result in deformity progression and neurologic symptoms, including paresthesias, incontinence, and the inability to walk.

• Genu varum

— The primary manifestation in the lower extremity

— May be asymptomatic or associated with knee pain or instability

— A lateral thrust may be evident with walking.

• Lumbosacral hyperlordosis

— May be seen during childhood in up to 80% of patients

— Secondary to increased pelvic tilt while standing

— Presents as a prominent abdomen and buttocks with hip flexion contractures

• Symptomatic spinal stenosis

— Occurs as a result of endochondral ossification defects along the entire spinal column, producing short, thickened pedicles and a narrowing of the interpediculate distance from L1 to L5 (Figure 72-1). Mismatch between the smaller spinal canal and the normal-sized neural elements increases risk for spinal stenosis.

— Occasionally develops during adolescence, but more often in adulthood

— Symptoms include leg pain; numbness, weakness, or frequent squatting to relieve pain as in neurogenic claudication; and neurologic incontinence.

• Flexion contractures of the elbow and subluxated radial heads

• Trident hand

— Extra space between first and second rays and third and fourth rays, with all fingers of nearly equal length

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