Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ Key Features +++ Essentials of Diagnosis ++ Clinical expression differs in male and female offspring depending on which parent is transmitting the gene The premutation can change into the full mutation only when passed through a female The most common inherited cause of intellectual disability +++ General Considerations ++ Present in approximately 1 in 1000 males The responsible gene is FMR1, which has unstable CGG repeats at the 5′ end Normal individuals have up to 50 CGG repeats Individuals with 51–200 CGG repeats have a premutation and may manifest symptoms Affected individuals with Fragile X syndrome (full mutation) have more than 200 CGG repeats and also have hypermethylation of both the CGG expansion and an adjacent CpG island +++ Clinical Findings ++ Intellectual disabilities Oblong facies with large ears Large testicles after puberty Other physical signs include hyperextensible joints and mitral valve prolapse Many affected individuals are hyperactive and exhibit behaviors along the autism spectrum Females with a full mutation may exhibit a phenotype ranging from normal IQ to intellectual disability and may show behaviors along the autism spectrum +++ Diagnosis ++ DNA analysis is a reliable test for prenatal and postnatal diagnosis and facilitates genetic counseling +++ Treatment +++ Nonpharmacologic ++ Speech and language therapy Can decrease oral hypersensitivity Improve articulation Enhance verbal output and comprehension Stimulate abstract reasoning skills Augmentative communication techniques may be helpful because approximately 10% of boys will be nonverbal at age 5 years Occupational therapy can be helpful in Providing techniques for calming hyperarousal to stimuli Improving the child's fine and gross motor coordination and motor planning If the behavioral problems are severe, it can be helpful to involve a behavioral psychologist who emphasizes Positive reinforcement Time-outs Consistency in routine Use of auditory and visual modalities, such as a picture schedule, to help with transitions and new situations Genetic counseling is an important component of management +++ Pharmacologic ++ Clonidine or guanfacine may be helpful in low doses to treat hyperarousal, tantrums, or severe hyperactivity Methylphenidate or dextroamphetamine Usually beneficial by age 5 years and occasionally earlier Relatively low doses are used because irritability is often a problem with higher doses Selective serotonin reuptake inhibitor (SSRI), such as fluoxetine Often helpful for anxiety May also decrease aggression or moodiness, although in approximately 25% of cases, an increase in agitation or activation may occur Clonidine, guanfacine, and an SSRI may decrease aggression, which may become a significant problem; atypical antipsychotic may be needed; counseling can be helpful in these cases +++ Outcome +++ Prognosis ++ Male carriers are at risk for fragile X tremor ataxia syndrome (FXTAS), a neurodegenerative disorder, as they age +++ When to ... Your MyAccess profile is currently affiliated with '[InstitutionA]' and is in the process of switching affiliations to '[InstitutionB]'. Please click ‘Continue’ to continue the affiliation switch, otherwise click ‘Cancel’ to cancel signing in. Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Username? Forgot Password? Sign in via OpenAthens Sign in via Shibboleth