RETT SYNDROME (OR RETT'S DISORDER)

Rett syndrome, also known as Rett’s disorder, is a progressive neurological disorder. It is one of the less common Autism Spectrum Disorders, also known as Pervasive Developmental Disorders. The symptoms of this disorder are easily confused with those of cerebral palsy. The clinical diagnosis specifies a small head and small hands and feet. Stereotypical repetitive hand movements such as mouthing or wringing of the hands are also included as diagnostic signs. Symptoms of the disease include learning disorders and a total inability to socialize. Girls with Rett syndrome are very prone to seizures and gastrointestinal disorders. They typically have no verbal skills, and about 50% of females are ambulatory.

Cause of rett syndrome

Rett syndrome is linked to the X chromosome so it almost exclusively affects girls. Development is normal until six to18 months of age, when language and motor milestones regress, purposeful hand use is lost and acquired microcephaly is seen. Hand-wringing and sighing are characteristic, and those affected develop autistic behavior. Rett syndrome is usually caused by a mutation in the gene encoding methyl-CpG-binding protein-2 (MECP2). Rett syndrome can also be caused by a mutation to the gene encoding cyclin-dependent kinase-like 5 (CDKL5). Rett syndrome affects around one 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.

The severity of Rett syndrome in females can vary depending on the pattern of X-chromosome inactivation. In most cases, 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 and most likely die very early, just as males with MECP2 mutations do, as they only have one X chromosome.

Some researchers 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 of rett syndrome

Infants with Rett syndrome typically develop normally until they are six to 18 months old. Physioneurological development tends to plateau after this brief period of normal development, and is followed by deterioration of the higher brain functions. Psychomotor and cognitive abilities rapidly decline between one to two years of age. Symptoms that develop are similar to those of Autism, including intellectual disability and poor growth. It is, hence, easy to mistakenly diagnose Rett syndrome for Autism, or cerebral palsy.

symptoms of rett syndrome

Symptoms of Rett syndrome that are similar to Autism include:
• screaming fits
• panic attacks
• inconsolable crying
• avoidance of eye contact
• lack of social/emotional reciprocity
• general lack of interest
• poor use of nonverbal communication
• delay of linguistic development
• loss of speech.

Symptoms of Rett syndrome that are also present in cerebral palsy include:
• short stature
• severe dementia
• mild learning disability
• hypotonia
• delayed or absent ability to walk
• gait/movement difficulties
• ataxia (unsteady walking)
• abnormally small head
• some forms of spasticity
• wringing of hands
• spasmodic movements of hand or facial muscles
• grinding of teeth.

Symptoms may stabilize for up to a few decades before complications set in, such as epilepsy or seizure and spastic paraparesis (spasticity or paralysis of the lower limbs).

Treatment and prognosis of rett syndrome

Currently there is no cure for Rett syndrome. Treatment of Rett disorder briefly includes increasing the patient’s communication skills, counseling, modifying social difficulties and behavioral interventions. Treatment may involve consultations from speech and language therapists, neuropsychologists, psychologists, counselors, neurologists, and neuropsychiatrists.
Common drug prescriptions include:
• antidepressants
• antipsychotics
• beta-blockers
• opioid antagonists.
Common assistive technology used may include wheelchairs or a standing frame.

mortality and rett syndrome

Males with pathogenic MECP2 mutations usually die during infancy stage from severe encephalopathy, unless they have an extra X chromosome (often described as Klinefelter’s syndrome), or have somatic mosaicism. Females can live up to 40 years or more. Abnormal lab data values on Rett disorder may show:
• EEG abnormalities from 2 years of age
• atypical glycolipids
• elevated levels of beta-endorphins and glutamate
• reduction of substance P
• decreased levels of nerve growth factors.

Mortality rate among children with Rett disorder is approximately at 1.2% per year. High proportion of deaths are abrupt; due to:
• heart conduction problem - abnormally prolonged QT interval on ECG
• spontaneous brainstem dysfunction
• respiratory arrest.

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This autism fact sheet is licensed under the GNU Free Documentation. It is derivative of an Autism and Asperger's syndrome-related articles at http://en.wikipedia.org