Rett syndrome

Rett syndrome (Rett syndrome, Rett's disorder) is a progressive neurological disorder. The symptoms of this disorder are easily confused with those of autism and cerebral palsy. The clinical diagnosis includes small head, hands, and feet. more...

Stereotypical repetitive hand movements such as mouthing or wringing are also included. Girls are very prone to seizures, GI disorders, and are typically nonverbal. About 50% of the girls/women are ambulatory.

Etiology

Rett syndrome (symbolized RTT) is X-linked dominant, affecting almost exclusively girls. Development is normal until 1 year of age, when language and motor milestones regress and acquired microcephaly is seen. Hand wringing and sighing are characteristic, and they develop autistic behavior. Rett syndrome is usually caused by a mutation in the gene encoding methyl-CpG-binding protein-2 (MECP2). MECP2 is found on chromosome band Xq28, near the long end of the X chromosome. Rett syndrome can also be caused by a mutation to the gene encoding cyclin-dependent kinase-like 5 (CDKL5). Rett syndrome affects 1 in every 12,500 female live births.

Gender and Rett syndrome

Most individuals with Rett syndrome are female. One explanation given for this was that the genetic defect that caused Rett syndrome in females caused embryonic lethality in males (that is, males with pathogenic MECP2 mutations died before they were born). While a plausible hypothesis, more recent research has contradicted this explanation.

Most males with a pathogenic MECP2 mutation suffer from neonatal encephalopathy and die within a year or so of birth. Males who have two X chromosomes and a Y chromosome (often called Klinefelter's syndrome), one with a mutated MECP2 gene, follow a similar development path to females with Rett syndrome. Males who have somatic mosaicism also have symptoms like females with Rett syndrome.

Some researchers (for example Masuyama et al 2005) have reported cases of males with Rett syndrome who have a pathogenic MECP2 mutation but do not have a somatic mosaicism or an extra chromosome.

Unlike most genetic diseases, many cases of Rett syndrome involve spontaneous mutations in one of the parent’s gonads. It has been argued that one cause of the majority of Rett syndrome individuals being female is that mutations to MECP2 are possibly more common in male gonads than female gonads, and only females can inherit a mutated MECP2 gene from fathers (males inherit a Y chromosome from fathers, which does not contain a copy of MECP2).

Development and Symptoms

Infants typically develop normally up to age 6-18 months. Physioneurological development tends to plateau after this brief period of normal development, and is followed by deterioration of high brain functions. Psychomotor and cognitive abilities rapidly decline within 1-2 years of age. Symptoms that develop are autistic-like, with mental retardation and poor growth. It is, hence, easy for the misdiagnosis of Rett for autism, or cerebral palsy.

Read more at Wikipedia.org