Genetics of X‐linked Mental Retardation


X‐linked mental retardation (XLMR) refers to a group of inherited disorders characterised by varying degrees of mental retardation, caused by mutations in various genes present on the X‐chromosome. Historically, XLMR is divided into syndromic (MRXS) and nonsyndromic (MRX). At least 209 different XLMR disorders have been described including 143 forms of syndromic mental retardation. Fragile X syndrome is the most frequent syndrome and most studied XLMR syndrome. It is now possible to identify 42% of the genetic defects in XLMR families with obligate female carriers. Most of the mutated genes in XLMR are thought to influence development, cell migration, formation and maintenance of neural networks and cell‐to‐cell communication in brain. Thus the diagnosis of mental retardation in a child has an enormous impact in most affected families. Genetic counselling is strongly recommended to family members.

Key Concepts:

  • X‐linked mental retardation (XLMR) is a very heterogeneous set of conditions responsible for a large proportion of inherited mental retardation.

  • XLMR can be divided into syndromic (MRXS) and nonsyndromic (MRX).

  • Genes involved in XLMR influence development, cell migration, formation and maintenance of neural networks and cell‐to‐cell communication in brain.

  • Mental retardation phenotype can emerge as the final common pathway of many different types of abnormal cellular processing.

  • Genetic counselling is an important part in general management in the case of mental retardation.

Keywords: X‐linked mental retardation; syndromic X‐linked mental retardation; nonsyndromic X‐linked mental retardation; fragile X syndrome; recurrence risk; genetic counselling

Figure 1.

The location of the 72 genes for XLMR syndromes which have been cloned and mutations demonstrated. Copyright Greenwood Genetic Center, updated July 2010.

Figure 2.

The location of the 19 MRX genes and the 17 genes that cause MRX and MRXS. Copyright Greenwood Genetic Center, updated July 2010.



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Further Reading

Raymond FL (2006) X linked mental retardation: a clinical guide. Journal of Medical Genetics 43: 193–200.

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Lisik, Małgorzata Zofia(Nov 2010) Genetics of X‐linked Mental Retardation. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020231]