Definition (Curr Genomics 2011;12:216; Clin Pediatr (Phila) 2005;44:371)
• X-linked dominant w/ ↓ penetrance. 2/2 abn complement of trinucleotide repeats
• Full mutation usually w/ phenotype. Mosaicism common
• Full mutation has >200 CGG repeats → absence of FMR-1 protein, which is responsible for the symptoms. The greater the repeats, the more severe the disease
• Occurs in both males and females
• Most common inherited cause of mental retardation
• Prevalence rate of 1:4,000 males, 1:8,000–9,000 females
Diagnosis
• Classic triad: Macro-orchidism, large or prominent ears, and a long narrow face
• Suspect dx in any infant or toddler w/ developmental delays (esp speech) or maternal FHx of MR, developmental disabilities or learning disabilities
• Males w/ full mutation: Global dev delays and MR, may have autistic spectrum disorder
• Physical exam: Look for macrocephaly, prominent forehead, hyperextensible joints, stretchy skin, MVP, and large testicles
• Females w/full mutation → mildly affected with normal development to MR
• FMR-1 gene is located on X chromosome
Medical Complications
• Have normal life expectancy; recent studies demonstrate stat sign increase in rate of obesity (31% compared to 18% in age-matched controls; associated w/ Prader–Willi phenotype)
• Recurrent otitis media and sinusitis
• MVP develops in adolescence or adulthood
• Hypotonia is common, may have seizures
• Macro-orchidism
• 
s tend to exhibit social avoidance. May have ADHD; benefit from early intervention