Psych Vivas · Intellectual disability — neurodevelopmental
Fragile X syndrome — structured clinical viva
Fellowship viva on FMR1 allele classes, Sherman paradox, full-mutation phenotype, FXTAS/FXPOI, molecular diagnosis, comorbidity care and cascade counselling.
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Target exams
Interpretation
Reveal interpretation
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]
Key points
[1] [2] [6]References
- [1]Hagerman RJ, Berry-Kravis E, Hazlett HC, et al. Fragile X syndrome Nat Rev Dis Primers, 2017.PMID 28960184
- [2]Hunter JE, Berry-Kravis E, Hipp H, Todd PK FMR1 Disorders GeneReviews, 1993.PMID 20301558
- [3]Fu YH, Kuhl DP, Pizzuti A, et al. Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox Cell, 1991.PMID 1760838
- [4]Cordeiro L, Ballinger E, Hagerman R, Hessl D Clinical assessment of DSM-IV anxiety disorders in fragile X syndrome: prevalence and characterization J Neurodev Disord, 2011.PMID 21475730
- [5]Jacquemont S, Hagerman RJ, Leehey MA, et al. Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population JAMA, 2004.PMID 14747503
- [6]Allingham-Hawkins DJ, Babul-Hirji R, Chitayat D, et al. Fragile X premutation is a significant risk factor for premature ovarian failure: the International Collaborative POF in Fragile X study Am J Med Genet, 1999.PMID 10208170