Rett Syndrome

Causes

Mutations that cause RS are sporadic and the gene for RS was only recently identified as (methyl-CpG binding protein-2 [MECP2]). In a family with one child who has RS, the increased risk of having a second child with RS is reportedly less than 0.4 percent. However, recurrence of RS can occur through such mechanisms as germline mosaicism. This is when the [Page 1490]presence of a gene mutation for a disease trait in some yet not all of the parents sexual reproductive cells.

Epidemiology

In the U.S. a large study found the incidence to be approximately one per 20,000 people.

Internationally, incidence varies widely with some reports as high as one per 10,000 live female births to that of Japan with one per 45,000 girls aged 6 to 14 years with RS. These variations in incidence may be from reporting of all variations of RS. These atypical forms include congenital RS, milder forms with later onset of regression, and preserved speech variants.

Most patients with RS survive into the fifth or sixth decade of life, often with severe disabilities. After the age of 10 survival rates decline. For example, a 35year survival rate is 70 percent. However, death may be sudden and secondary to pneumonia or other long term illness with such risk factors as seizures, loss of mobility, and difficulties with swallowing. Life expectancy worldwide is favorable in those with RS than in other individuals with profound mental handicap.

However, there is an obvious sex relation to RS with that of females as it is X-linked. This means that disease is tied to the X chromosome, which is one of the sex chromosomes that determine gender. Males have one X and one Y chromosome, while females have two X chromosomes. As with many X-linked disease, most males are thought to die while in the womb. However, some cases do exist of males with mutations similar to those found with MECP2 and exhibit RS symptoms. Males with this disorder also show a wide range of symptoms from severe congenital encephalopathy, muscle spasm, involuntary muscle movements and mild mental retardation.

Signs and Symptoms

Patients with RS initially have what looks like healthy development. In retrospect upon investigation, girls are reported by parents to have been placid as infants, with low muscle tone and subtle slowing of normal development. One clinical feature is slow head growth between 2 to 4 months of age can be common. A period of developmental stagnation is followed by a period of regression.

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