Rett syndrome

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Rett syndrome
Classification & external resources
ICD-10 F84.2
ICD-9 330.8
OMIM 312750
DiseasesDB 29908
eMedicine med/3202 
MeSH C10.574.500.775

Rett syndrome is a neurodevelopmental disorder that is classified as a pervasive developmental disorder by the DSM-IV. Many argue that this is a mis-classification just as it would be to include such disorders as fragile X syndrome, tuberous sclerosis, or Down syndrome where one can see autistic features. The symptoms of this disorder are most easily confused with those of Angelman syndrome and autism. The clinical features include a deceleration of the rate of head growth (including microcephaly in some) and small hands and feet. Stereotypic, repetitive hand movements such as mouthing or wringing are also noted. Symptoms of the disease include cognitive impairment and problems with socialization, the latter during the regression period. Socialization typically improves by the time they enter school. Girls with Rett syndrome are very prone to gastrointestinal disorders and about 30% have seizures. They typically have no verbal skills, and about 50% of females are not ambulatory. Scoliosis, growth failure, and constipation are very common and can be problematic.

Contents

[edit] Cause

Rett syndrome (symbolized RTT) is X-linked dominant, affecting almost exclusively girls. Development is normal until 6-18 months, when language and motor milestones regress, purposeful hand use is lost and acquired deceleration in the rate of head growth (resulting in microcephaly in some) is seen. Hand stereotypies are typical and breathing irregularities such as hyperventilation, breathholding, or sighing are seen in many. Early on, autistic-like behavior may be seen. Rett syndrome is usually caused (95% or more) by a mutation in the gene encoding methyl-CpG-binding protein-2, MECP2. MECP2 is found near the end of the long arm of the X chromosome at Xq28. An atypical form of Rett syndrome, characterized by infantile spasms or early onset epilepsy, can also be caused by a mutation to the gene encoding cyclin-dependent kinase-like 5 (CDKL5). Rett syndrome affects one in every 12,500 female live births by age 12 years.

[edit] 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. The incidence of Rett in males is unknown.[1]

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

The severity of Rett syndrome in females can vary depending on the type and position of the MECP2 mutation and the pattern of X-chromosome inactivation. In most cases,[citation needed] 50% of cells use the maternal X chromosome while the other 50% uses the paternal X chromosome. However, if most cells in the brain activate the X chromosome with the functional MECP2 allele, the individual will have very mild Rett syndrome; likewise, if most neurons activate the X chromosome with the mutated MECP2 allele, the individual will have very severe Rett syndrome just as males with MECP2 mutations do (as they only have one X chromosome).

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, most individuals with Rett syndrome result from spontaneous mutations in one of the parent’s gametes. It has been argued[citation needed] that one cause of the majority of Rett syndrome individuals being female is that MECP2 mutations are more common in sperm cells, 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).

[edit] Development and symptoms

Infants with Rett syndrome typically develop normally until they are 6-18 months old. Neurological development tends to plateau after this brief period of normal development, and is followed by regression of previously acquired skills. Psychomotor abilities rapidly decline between 1-2 years of age. Early features are similar to those of autism. It is, hence, easy to mistakenly diagnose Rett syndrome for autism.

Symptoms of Rett syndrome that are similar to autism:

  • screaming fits
  • panic attack
  • inconsolable crying
  • avoidance of eye contact
  • lack of social/emotional reciprocity
  • general lack of interest
  • markedly impaired use of nonverbal behaviors to regulate social interaction
  • loss of speech

Symptoms of Rett syndrome that are also present in cerebral palsy (regression of the type seen in Rett syndrome would be unusual in cerebral palsy; this confusion should rarely be made):

Symptoms may stabilize for many decades, particularly for interaction and cognitive function such as making choices. Motor functions may slow as ridigity and dystonia appear. Seizures may be problematic, with a wide range of severity. Scoliosis occurs in most and requires corrective surgery in about 10%. Those who remain ambulatory tend to have less progression of scoliosis.

[edit] Treatment and prognosis

Please help improve this section by expanding it.
Further information might be found on the talk page or at requests for expansion.
This article has been tagged since February 2007.

Currently there is no cure for Rett syndrome, although there has been some promising results with gene therapy in mice.[2]

Treatment of Rett syndrome includes:

  • management of gastrointestinal (reflux, constipation) and nutritional (poor weight gain) issues
  • prevention of seizures
  • surveillance of scoliosis and prolonged QT syndrome
  • increasing the patient's communication skills, especially with augmentative communication strategies
  • parental counseling
  • modifying social difficulties
  • behavioral interventions
  • finding an effective way for the girl to communicate effectively

Treatment usually requires consultations from:

Common drug therapies include:

Common assistive technology used:

[edit] Mortality

Males with pathogenic MECP2 mutations usually die within first 2 years from severe encephalopathy, unless they have an extra X chromosome (often described as Klinefelter syndrome), or have somatic mosaicism.

Females can live up to 60 years or more. Abnormal lab studies on Rett syndrome may show:

A high proportion of deaths are abrupt, but most have no identifiable cause; in some instances death is the result most likely of:

[edit] Notes

A new study found a reversal of neurological defects in a mouse model of Rett Syndrome! http://www.sciencemag.org/cgi/content/abstract/1138389v1?etoc

  1. ^ "New Study Reveals Rett Syndrome Can Strike Males" ScienceDaily [1] August 12, 2006
  2. ^ "Autism-like disorder 'reversible'" [2] 8 February 2007.

[edit] References

[edit] External links


v • d • e
Pervasive developmental disorders / Autistic spectrum

Diagnoses

Autism | Asperger syndrome | Semantic Pragmatic Disorder | Hyperlexia | Autistic enterocolitis | Childhood disintegrative disorder | Conditions comorbid to autism | Fragile X syndrome
Rett syndrome | PDD-NOS | Sensory Integration Dysfunction | Multiple-complex Developmental Disorder

Controversies

Andrew Wakefield | Incidence | Autism rights movement | Biomedical intervention | Causes | Chelation
Generation Rescue | Heritability | Neurodiversity | Refrigerator mother | Therapies

List of autism-related topics

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