Fragile X syndrome — structured clinical viva

What is FXS / inheritance? Most common inherited monogenic ID. X-linked FMR1 CGG expansion. Full mutation typically greater than 200 repeats with methylation and FMRP loss. Boys usually affected; girls variable. Full mutations almost always come via mother.^[1][2]

CGG numbers. Normal ~5–44; intermediate ~45–54; premutation ~55–200; full mutation greater than 200. Premutation ≠ mild FXS. Sherman paradox: expanding alleles across generations, especially maternal transmission.^[2][3]

Mother's early menopause. Suggests possible premutation with FXPOI risk — established association with premature ovarian failure/insufficiency. Needs genetic counselling and reproductive discussion, not dismissal as coincidence.^[6][2]

Cure medicine? No approved routine disease-modifying core cure restoring FMRP. Supports + treat anxiety/ADHD/seizures/behaviour risk. Experimental mGluR-targeted ideas exist as theory, not standard cure claims.^[1][2]

Psychiatric watch-list. Anxiety (very high), ADHD symptoms, ASD features, sensory hyperarousal, sleep, mood; seizures in a minority. Adapt MSE for sensory load.^[4][1]

Who else to test? Cascade testing/counselling for mother and other at-risk maternal-line relatives; adult premutation carriers need awareness of FXTAS with ageing (tremor/ataxia/executive decline) and FXPOI in women.^[2][5][6]

Name evidence. Hagerman 2017 primer; GeneReviews FMR1 disorders; Fu 1991 Sherman; Cordeiro 2011 anxiety; Jacquemont 2004 FXTAS penetrance; Allingham-Hawkins 1999 POF.^{[1][2][3][4][5][6]}