Snapshot A 5-year-old boy is brought to his pediatrician. He is mentally retardarded, has a prominant jaw, large soft ears, and large testicles. Introduction X-linked genetic abnormality trinucleotide repeat (CGG) on FMR1 gene of the X-chromosome may show genetic anticipation, but family history of disease may not be present anticipation is the expansion of the trinucleotide repeat in future generations resulting in more severe symptoms caused by defect affecting the methylation and expression of the FMR1 gene Epidemiology second most common cause of mental retardation most common cause of mental retardation in boys Presentation Symptoms symptoms and/or behavioral problems may develop at birth or afterwards many children experience exacerbation of such problems during puberty, as mentioned below Physical exam behavior problems may be evident including delay in movement (i.e. crawling, ambulation,rolling) hyperactive behavior (impulsive, repetitive, ritualistic) signs of mental retardation and/or disability autism spectrum disorder (speech and language disorders) physical signs indicative of syndrome may be evident including flattened feet flexible joints low muscle tone enlarged body habitus enlarged, elongated foreheads, long face low-set and/or enlarged ears pectus excavitatum soft skin macro-orchidism (enlarged testicles) mitral valve prolapse Evaluation Diagnosis is based primarily on clinical observation and family history Head circumference may be larger than average at birth Genetic studies may confirm Fragile X syndrome number of gene repeats can provide insight into anticipating severity of disease Differential Cerebral palsy, Down syndrome, other syndromic disorders Treatment Medical management there are no specific treatments for Fragile X syndrome special education and training indicated in all cases to achieve highest level of function possible Prognosis, Prevention, and Complications Prognosis ranges widely and depends highly on the level of mental disabilty/retardation Prevention there are no preventive measures for this disorder genetic counseling could be of value for reproductive health Complications recurrent infections, seizure disorders, and potentially autism, though not in all cases