RT Book, Section A1 Schneider, Gretchen A2 Murray, Michael F. A2 Babyatsky, Mark W. A2 Giovanni, Monica A. A2 Alkuraya, Fowzan S. A2 Stewart, Douglas R. SR Print(0) ID 1102706772 T1 Fragile X Syndrome and Related Conditions T2 Clinical Genomics: Practical Applications in Adult Patient Care YR 2014 FD 2014 PB McGraw-Hill Education PP New York, NY SN 9780071622448 LK accessbiomedicalscience.mhmedical.com/content.aspx?aid=1102706772 RD 2024/03/28 AB Disease summary:Fragile X syndrome is characterized by neurodevelopmental dysfunction including intellectual disability and behavioral problems, facial dysmorphism, and connective tissue findings. Clinical features may be subtle in childhood while developmental delays typically present at a young age. Manifestations in affected females tend to be milder than those seen in males.Fragile X-associated late-onset tremor-ataxia syndrome (FXTAS) is a progressive neurodegenerative disorder that typically presents after age 50 and affects men more commonly than women.Fragile X-associated premature ovarian insufficiency (FXPOI) can present as decreased ovarian reserve, decreased fertility, elevated follicle-stimulating hormone (FSH) levels, or premature ovarian failure (POF).Hereditary basis:Fragile X syndrome, FXTAS, and FXPOI are caused by triplet repeat expansions in the FMR1 gene on the X chromosome.Greater than 99% of fragile X syndrome is associated with repeat sizes of greater than 200 (full mutation). Less than 1% is associated with other mutations that silence the FMR1 gene.FXTAS and FXPOI are associated with repeat sizes of 55 to 200 (premutation)Females with a pre or full mutation have a 50% of passing an expansion mutation to their offspring.Expansion of a premutation to a full mutation only occurs during female meiosis and depends on premutation size in carrier females.Fragile X syndrome affects approximately 1/4000 males and 1/8000 females. The carrier frequency for FMR1 premutations in females in the United Statesis estimated to be 1/382.Differential diagnosis:Fragile X syndrome is the most common single gene cause of intellectual disability and autism. Therefore, it should be considered at the top of the differential diagnosis for males and females affected with either of the two.Intellectual disability is seen as a part of many genetic syndromes, however, the presence of clinical features consistent with other conditions may help to rule out other diagnoses.Genetic conditions that warrant consideration when a diagnosis of fragile X syndrome cannot be established include fragile XE syndrome, Sotos syndrome, and other chromosomal abnormalities.