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Fragile X syndrome: Clinical features and diagnosis in children and adolescents

Hilde Van Esch, MD, PhD
Section Editors
Helen V Firth, DM, FRCP, DCH
Carolyn Bridgemohan, MD
Deputy Editor
Elizabeth TePas, MD, MS


Fragile X syndrome (FXS) is an X-linked disorder and the most common inherited cause of intellectual disability [1]. Both males and females can be affected.

The clinical features and diagnosis of FXS (previously called fragile X mental retardation syndrome, X-linked mental retardation and macro-orchidism, and Martin-Bell syndrome) in children and adolescents are discussed in this topic review. Prenatal screening and the management of FXS in children and adolescents are discussed separately. (See "Prenatal screening and diagnosis for fragile X syndrome" and "Fragile X syndrome: Management in children and adolescents".)


FXS (MIM #300624) is the most frequent form of inherited intellectual disability, with a prevalence of the full mutation between 1 in 4000 and 1 in 7000 in males [1-3]. The prevalence of the full mutation in females is approximately two-thirds to one-half of that in males [2,3]. The premutation carrier rate is approximately 1 in 750 to 1 in 850 men and 1 in 250 to 1 in 300 in women [1,3-5]. FXS has been diagnosed in up to 3 percent of boys with significant neurodevelopmental disorders (eg, autism, nonsyndromic intellectual disability) [6].


FXS is an X-linked disorder. It is caused by decreased or absent levels of fragile X mental retardation protein (FMRP) due to a loss-of-function mutation in the fragile X mental retardation 1 (FMR1) gene, located at Xq27.3 [7,8]. In more than 99 percent of cases, loss of function is caused by an unstable expansion of a trinucleotide (cytosine-guanine-guanine, CGG) repeat at the 5' untranslated region [2,9]. Deletions, point mutations, and missense mutation in FMR1 also may cause FXS but are rare [2,10,11].

There are two clinically significant levels of CGG expansion:


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Literature review current through: Sep 2016. | This topic last updated: Mar 15, 2016.
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