Overview
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Results from overactive FGFR3, leading to inhibition of cartilage proliferation, leading to characteristic disproportionate dwarfism with relative macrocephaly, frontal bossing, midface hypoplasia, spine deformations, long narrow trunk, short extremities, and trident hands.
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Average adult height is 4 feet 4 in. for males, 4 feet 1 in. for females.
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Average adult weight is 120 lbs (55 kg) for males, 100 lbs (45 kg) for females.
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Atlantoaxial instability, cervicomedullary compression, foramen magnum or spinal stenosis leading to cord compression and cauda equina syndrome may require neurologic intervention.
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Brainstem compression contributes to central apnea while midface structural abnormalities lead to obstructive sleep apnea.
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Kyphoscoliosis and rib cage deformities lead to restrictive lung disease.
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Chronic hypoxia and hypercarbia from restrictive lung disease and sleep apnea lead to pulmonary hypertension and cor pulmonale.
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Increased mortality from resp and neuro complications during childhood.
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Heart-disease-related mortality approaches 10 times the general population in ages 25 to 35.
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Intelligence is usually normal; overall life expectancy is decreased by 10 y.
Etiology
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Caused by mutation of FGFR3 on chromosome 4p.
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>80% of cases are spontaneous gene mutations.
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Autosomal dominant trait with complete penetrance (heterozygous parent has a 50% chance of passing on the altered gene).
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Homozygous fatal in first few wk due to severe resp or neuro impairment.
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Advanced paternal age (age >35 y) is a risk factor in de novo cases.
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