Snapshot A 3-year-old boy is brought to a pediatrician. His past medical history is unknown, as this is his first visit to the pediatrician. His mother reports that the family prefers an isolated existence and therefore has not sought medical help. However, she reports being concerned about his learning abilities, as his speech appears delayed compared to his sisters. On physical exam, the boy has a prominently long face, large jaw, and large ears. The pediatrician recommends a genetic test. 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 risk factors family history 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 Prognosis life span is normal 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