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