Fragile X Syndrome

Excerpt

Fragile X syndrome (FXS), also known as Martin-Bell syndrome in the past, is a non-Mendelian trinucleotide repeat disorder. FXS is the most prevalent inherited cause of mild-to-severe intellectual disability and the most common monogenic cause of autism spectrum disorder. It accounts for about one-half of cases of X-linked intellectual disability and is the most common cause of mental impairment after trisomy 21. Physical features include a long, narrow face with a prominent jaw and forehead, hyperflexible fingers, and large ears. After puberty, enlarged testicles may be present in males. About a third of these children have features of autism and delayed speech that are present from an early age. Hyperactivity and seizures are common.

FXS testing should be a consideration in the differential diagnosis of any individual with intellectual disabilities, impaired development, or autism of unknown etiology. In addition, all individuals older than 50 years with ataxia and tremors or females with premature ovarian insufficiency should be tested for this premutation. Molecular genetic tests, rather than cytogenetics, are now used to diagnose FXS. The number of cytosine-guanine-guanine (CGG) repeats is measurable using polymerase chain reaction (PCR); methylation status is detected by Southern blot analysis. There is no cure for the disease, but early diagnosis and intervention can improve patients' and families' prognosis and quality of life and aid them in their future reproductive decisions.

Unfortunately, clinicians frequently do not diagnose this condition due to several factors, including similar clinical features as other syndromes, various presenting phenotypes, and frequent absence of clinical features at birth. Therefore, FXS is underdiagnosed, leading to suboptimal management and patient outcomes. This activity for healthcare professionals aims to enhance learners' competence in identifying the indications for diagnostic testing, selecting appropriate diagnostic tests, managing and counseling patients diagnosed with FXS, and fostering effective interprofessional teamwork to improve outcomes.