Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 40-18: Fragile X Mental Syndrome + Key Features Download Section PDF Listen +++ ++ Accounts for more cases of mental impairment in males than any condition except Down syndrome Inherited as an X-linked condition About 1 in 4000 males is affected The CNS phenotype includes autism spectrum, impulsivity and aggressiveness, and repetitive behaviors Heterozygous women have variable phenotypes that range from mental impairment to premature ovarian failure to essentially normal, in large part dependent on the number of repeated trinucleotides present + Clinical Findings Download Section PDF Listen +++ ++ Affected males have Macro-orchidism (enlarged testes) after puberty Large ears and a prominent jaw, high-pitched voice, autistic characteristics, and mental impairment Evidence of a mild connective tissue defect, with joint hypermobility and mitral valve prolapse Affected (heterozygous) women show no physical signs other than premature ovarian failure (early menopause), but they may have learning difficulties, anxiety, sensory issues, or frank retardation Premutation carriers (men and women with 55–200 CGG repeats) may develop ataxia and tremor as older adults + Diagnosis Download Section PDF Listen +++ ++ Cytogenetic studies demonstrate a small gap, or fragile site, near the tip of the long arm of the X chromosome Fragile site is due to expansion of a trinucleotide repeat (CGG) near a gene called FMR1 One FMR1 allele with ≥ 200 repeats results in mental impairment in virtually all men and learning difficulties in 60% of women Clinical DNA diagnosis for the number of CGG repeats can be performed for any male or female who has unexplained mental impairment Prenatal DNA diagnosis can be performed + Treatment Download Section PDF Listen +++ ++ No specific treatment has been developed Valproic acid may reduce symptoms of hyperactivity and attention deficit, but standard therapies should be tried first