Genetics of X‐Linked Intellectual Disability


X‐linked intellectual disability (XLID), formerly called mental retardation, refers to a group of inherited disorders characterised by varying degrees of intellectual disability caused by mutations in various genes present on the X‐chromosome. Deleterious mutations in 10% of X‐chromosome X genes are implicated in causing XLID disorders in 50% of families. The remaining XLID genes are expected to be rare and even private to individual families. Historically, XLID is divided into syndromic (IDXS) and nonsyndromic (IDX). At least 209 different XLID disorders have been described including 143 forms of syndromic mental retardation. Fragile X syndrome is the most frequent syndrome and most studied XLID syndrome. It is now possible to identify 64% of the genetic defects in XLID families with obligate female carriers. Most of the mutated genes in XLID are thought to influence development, cell migration, formation and maintenance of neural networks and cell‐to‐cell communication in the brain. Thus, the diagnosis of intellectual disability in a child has an enormous impact in most affected families. Genetic counselling is strongly recommended to family members.

Key Concepts

  • X‐linked intellectual disability (XLID) is a very heterogeneous set of conditions responsible for a large proportion of inherited mental retardation.
  • XLID can be divided into syndromic (MRID) and nonsyndromic (IDX).
  • Genes involved in XLID influence development, cell migration, formation and maintenance of neural networks and cell‐to‐cell communication in the brain.
  • Intellectual disability phenotype can emerge as the final common pathway for many different types of abnormal cellular processing.
  • Genetic counselling is an important part in general management in the case of intellectual disability.

Keywords: X‐linked intellectual disability; syndromic X‐linked intellectual disability; nonsyndromic X‐linked intellectual disability; fragile X syndrome; recurrence risk; genetic counselling

Figure 1. The location of the 72 genes for XLID syndromes which have been cloned and mutations demonstrated. Copyright Greenwood Genetic Center, updated July 2010.
Figure 2. The location of the 19 IDX genes and the 17 genes that cause MRX and MRXS. Copyright Greenwood Genetic Center, updated July 2010.


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Further Reading

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Lisik, Małgorzata Z(Nov 2017) Genetics of X‐Linked Intellectual Disability. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020231.pub2]