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Exploring the Genetic Causes of Rett Syndrome

written by: Emma Lloyd • edited by: Paul Arnold • updated: 7/14/2010

Rett syndrome develops as the result of a spontaneous genetic mutation, and leads to delayed physical and intellectual development. This article discusses the genetic causes of Rett syndrome and explains why it is unusual for this syndrome to run in families.

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    Rett syndrome is a brain development disorder which causes severe developmental delay in learning, communication, and physical coordination, and can cause scoliosis, sleep disturbances, and seizures. All of these signs and symptoms stem from mutations in a single gene, known as MECP2.

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    About the MECP2 Gene

    MECP2 is a gene which codes for a protein called methyl-CpG-binding protein-2. This protein is involved in controlling the expression of many other genes, and normal MECP2 function is essential for normal brain development.

    The MECP2 gene is located on the X chromosome, meaning that girl children have one mutated copy of the gene, and one normal copy. In contrast, male children have only one mutated copy, and no normal copy. This is why the disorder is usually noted in girl children and not in boys: male fetuses with a mutated MECP2 gene almost always die before birth, or shortly afterwards.

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    How Mutations in MECP2 cause Rett Syndrome

    All known causes of Rett syndrome are genetic in nature, but not all of these genetic causes are identical. To date two different types of MECP2 gene mutations have been determined to cause Rett syndrome: sequence variant mutations, and gene deletion mutations.

    Most cases of Rett syndrome are the result of sequence variations in the MECP2 gene which result in the production of a non-functional protein. The sequence of a gene refers to the sequence of the component molecules from which it is made, known as nucleotides. A normal copy of the MECP2 gene has a particular nucleotide sequence which, when altered, causes the gene to malfunction.

    In a small number of cases, Rett syndrome is the result of the deletion of part or the entire MECP2 gene, leading to the production of a non-functional protein, or none at all.

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    Does Rett Syndrome Run in Families?

    In more than 99% of cases, Rett syndrome is caused by a de novo mutation, which means that it is a spontaneous mutation, rather than one which has been inherited from a parent. Parents of a child with Rett syndrome almost always have intact, non-mutated MECP2 genes. This means that it is very unusual for Rett syndrome to run in families. When a child is born with Rett syndrome in a family with no other members affected by the disorder, the chances of a second child having the syndrome are well under 1%.

    There are, however, other genetic causes of Rett syndrome, accounting for the small number of cases in which the disorder does run in families. In very rare cases, some female family members have a mutation in the MECP2 gene, but do not have any Rett syndrome symptoms. These women are asymptomatic female carriers and have a risk of having a child with Rett syndrome.

    Genetic testing is usually recommended for sisters of girls who have Rett syndrome, to determine whether they are asymptomatic carriers.

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    References

    International Rett Syndrome Foundation: About Rett Syndrome

    National Institute of Child Health and Development: What causes Rett Syndrome? (PDF)

    National Institute of Health Genetics Home Reference: What is Rett Syndrome?

    National Institute of Neurological Disorders and Stroke: Rett Syndrome Fact Sheet

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