Rett syndrome is a rare neurodevelopmental disorder that almost exclusively affects girls. It is estimated to occur in nearly one of every 10,000 female births.
The genetic condition affects brain function and results in cognitive, emotional, sensory, and motor disturbances, as well as problems with the heart, breathing, and digestion.
Children with Rett usually experience regression or the loss of previously acquired skills, beginning in most girls between ages 6-18 months. While symptoms vary widely among patients, most will lose their ability to walk and to communicate.
There are no approved treatments for Rett, though some potential therapies are in clinical trials.
About 90–95% of Rett syndrome cases are caused by a mutation, or a change in DNA, in the MECP2 gene, which provides instructions to make the MECP2 protein. This protein regulates the activity of other genes by switching them on or off, and plays a critical role in brain development and function.
The MECP2 gene is located on the X chromosome. Since females have two X chromosomes, they still have one functional copy of MECP2 even if the other is mutated. Because males have only one X chromosome, they usually do not survive early infancy if they have a mutation in this gene. Very rarely, Rett syndrome occurs in boys with a different mutation; in those cases, it leads to intellectual and developmental problems.
More than 200 mutations have been identified in the MECP2 gene. In most cases, mutations in this gene occur spontaneously, which means they occur randomly. Rett syndrome can be inherited, but this is very rare — in fact occurring in less than 1% of cases.
The specific type of mutation in MECP2 is thought to affect disease severity.
There also are atypical forms of Rett, which include the early onset seizure type, also called the Hanefeld variant. Primarily caused by mutations in the CDKL5 gene, children with the Hanefeld variant usually start having seizures in the first months of life.
A congenital variant — called the Rolando variant — also begins early. Commonly caused by mutations in the in FOXG1 gene, the Rolando variant is characterized by early loss of muscle tone and severe developmental delays. The late childhood regression form, meanwhile, is characterized by later and more gradual regression of language and motor skills than is found in classic Rett.
In the preserved speech form, known as the Zappella variant, children regain language and motor skills, but show most symptoms of classic Rett syndrome.
Children with Rett do not show any symptoms at birth. The first complications usually appear between 6 to 18 months of life and are often subtle at their onset. Many may be overlooked. Some infants may show delays in gross motor skills, such as crawling or sitting, and reduced eye contact.
Between ages 1 and 4, children usually show a decline in verbal language abilities, often speaking less, and also start demonstrating fewer purposeful hand or fine motor skills. Stereotypic, or repetitive, hand movements and breathing irregularities also may occur at this stage. Irritability and slowed head growth are other possible symptoms at this age range.
The disease usually reaches a steady state between ages 2 and 10. This phase is marked by frequent seizures. Irritability and autistic-like symptoms such as loss of communication may ease.
The last stage of the disease, which can last for years or decades, is characterized by muscle weakness, scoliosis — an abnormal sideways curvature of the spine — and reduced mobility.
Apart from the MECP2 gene, mutations in the CDKL5 or FOXG1 gene also have been linked to Rett syndrome. However, those mutations cause atypical types of the disease.
However, as MECP2 mutations are not exclusive to Rett syndrome, clinical diagnostic criteria also are used. These include:
- Impairment of acquired speaking skills
- Loss of acquired purposeful hand skills
- Stereotypic hand movements
- Gait abnormalities, with low or no ability to walk
While there is no cure for Rett, currently used treatments focus on symptom relief and quality of life improvement. Therapy is multidisciplinary and addresses breathing irregularities, motor difficulties, seizures — usually treated with anticonvulsant medications — scoliosis, possible heart abnormalities, and other complications.
Nutritional supplements are used to ensure that patients have an adequate calorie intake and weight.
Splints and braces can help with scoliosis and may improve motor hand skills. Occupational therapy can help develop the skills needed for daily activities, such as dressing or feeding.
Physiotherapy may improve mobility and posture, while speech and language therapy may help with communication.
Family members may need psychosocial support.
Last updated: April 14, 2021
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