Snapshot A 4-year-old girl is brought to the pediatrician for evaluation of learning issues. Her mother reports that there is a family history of intellectual disability in the men in her family, but she is unsure what that syndrome is. On physical exam, the patient has a mildly long face and slightly prominent ears. Tests show that her speech and language skills are delayed for her age. She is referred to speech and language therapist as well as genetic testing for suspected fragile X syndrome. Introduction Overview fragile X syndrome is an X-linked dominant disorder characterized by macroorchidism, characteristic facial features, intellectual disability, and miral valve prolapse, caused by trinucleotide repeat (CGG) on the FMR1 gene Epidemiology Incidence the most common cause of inherited intellectual disability Demographics females have less impairment and less physical features typical of fragile X syndrome male > female Risk factors family history ETIOLOGY Genetics inheritance pattern X-linked dominant inheritance with variable penetrance mutations gene trinucleotide repeat in FMR1 gene resulting in decreased expression CGG repeats Associated conditions medical conditions and comorbidities mitral valve prolapse gastroesophageal reflux disease Presentation Symptoms common symptoms symptoms and behavioral problems may develop at birth of afterwards characterized by developmental, cognitive, and neuropsychiatric issues developmental developmental delay in motor, speech, and language skills cognitive low IQ neuropsychiatric autism-like behaviors hand flapping avoidance of eye contact anxiety behavioral issues aggression attention deficits oppositional tantrums seizure disorders Physical exam inspection facial features long face large jaw large everted ears pectus excavatum scoliosis protruding chin post-pubertal macroorchidism hyperextensible joints heart murmur or click mitral valve prolapse Imaging Radiograph indications evaluate for scoliosis findings scoliosis Echocardiograph indications evaluate for mitral valve prolapse findings mitral valve prolapse Studies DNA testing is diagnostic Southern blot test polymerase chain reaction Differential Autism spectrum disorder (ASD) key distinguishing factor similar behaviors such as hand flapping and avoidance of eye contact patients with ASD lacks physical features typical of fragile X syndrome Treatment Treatment is aimed at symptomatic management Lifestyle specialist therapists indications speech and language therapy occupational therapy physical therapy behavioral therapy Medical proton pump inhibitors indications gastroesophageal reflux disease Complications Recurrent infections Seizure disorders Prognosis Life span is normal