By: Rahima Olatinwo
What is Rett syndrome?
Rett syndrome (RTT) is a rare neurological disorder that negatively affects intellectual, speech, and motor development.
The Genetics of Rett Syndrome
Rett syndrome is primarily caused by a genetic mutation of the MECP2 gene. The MECP2 gene encodes for a protein necessary for the proper development of the brain. When there is a mutation of the MECP2 gene, this can result in developmental delays. Those with Rett’s rarely inherit the mutation from their parents. It usually occurs spontaneously in children.
Rett syndrome is X-linked dominant and seen primarily in females. It occurs in 1 in every 10,000 to 15,000 girls. The MECP2 gene is found on the X chromosome. Females have two copies of the MECP2 gene (one from the mother and one from the father), and males have one copy (one from the mother). Females with Rett’s will typically have one mutated gene and one normal gene. Rett is rarely seen in males. Since they only have one copy of the gene, a mutated copy of that gene usually means the child is unable to develop properly and has a very low chance of survival.
What to Look For
Children with Rett syndrome develop normally for the first six months of their lives. Then, they will start to show symptoms of delayed development. These symptoms are grouped into four stages. These stages aren’t rigid. Stages can overlap, and some kids may only show a few of these symptoms.
Stage 1 (6-18 months): Early Onset
Low muscle tone (hypotonia)
Reduced interest in toys
Loss of eye contact
Difficulties sitting, crawling, or walking
Slow head growth (microcephaly)
Stage 2 (1-4 years): Regression
Decline in speech and intellectual ability
Loss of muscle coordination (ataxia) and hand use
Social withdrawal
Repetitive hand movements like hand wringing, hand washing, clapping, tapping or hand mouthing (constantly moving hands to mouth)Irregular breathing
Problems sleeping
Irritability/screaming and crying fits
Stage 3 (2-10 years): Plateau
Improvements in eye contact, social interactions, and behavior
Stiff muscles (spasticity)
Teeth grinding (bruxism)
Seizures
Stage 4 (10+ years): Deterioration of Movement
No change in intellectual/cognitive ability or social/communication skills
Loss in mobility and inability to walk
Muscle weakness
Scoliosis
More about Seizures in Rett Syndrome
Seizures are a very common symptom of RTT. Those with RTT can have all seizure types; however, complex partial, generalized tonic-clonic, tonic, and myoclonic seizures are more common than clonic or absent seizures.
Similar Conditions
The symptoms of Rett syndrome can resemble those of…
Autism: difficulty making eye contact, social withdrawal
Angelman syndrome: difficulty walking, seizures, decline in speech and intellectual ability, stiff muscles
Cerebral palsy: seizures, speech delay, loss of muscle coordination, stiff muscles
Treatment and Management
There are no cures for Rett syndrome currently. However, it is possible to manage the symptoms with antiepileptic drugs, vagus nerve stimulation (VNS), speech therapy, behavioral therapy, and physical therapy.
In 2023, trofinetide (Daybue) was certified FDA-approved to help manage the symptoms of children 2 years and older. It is currently the only approved pharmaceutical designed to treat RTT.
Conclusion
Rett syndrome, or RTT, is a genetic neurodevelopmental condition that affects primarily young girls. The symptoms of RTT usually involve motor, speech, and intellectual decline. Intellectual ability does stabilize, but motor functions continue to deteriorate. Seizures are common but can be managed with anti-epileptic medications or therapies like VNS. Daybue has recently been approved for the treatment of RTT symptoms, so this gives hope for future medications and therapies for those with Rett Syndrome.
References
Bernstein, B. E. (2023, March 20). Rett Syndrome: Practice Essentials, Background,Pathophysiology and Etiology (C. Pataki, Ed.). Medscape. https://emedicine.medscape.com/article/916377-overview?form=fpf
NIH Office of Communications. (2022, January 18). What are the types & phases of Rett syndrome? Eunice Kennedy Shiver National Institute of Child Health and Human Development. https://www.nichd.nih.gov/health/topics/rett/conditioninfo/types
Operto, F. F., Mazza, R., Pastorino, G. M. G., Verrotti, A., & Coppola, G. (2019). Epilepsy and genetic in Rett syndrome: A review. Brain and Behavior, 9(5), e01250. https://doi.org/10.1002/brb3.1250
Percy, A. K. (2014). Rett’s Syndrome. Encyclopedia of the Neurological Sciences, Vol. 4, 29–33. https://doi.org/10.1016/b978-0-12-385157-4.01051-4
Rett Syndrome – Symptoms, Causes, and Treatment | NORD. (2023, March 15). Rarediseases.org. https://rarediseases.org/rare-diseases/rett-syndrome/#symptoms
Rett Syndrome | National Institute of Neurological Disorders and Stroke. (2023, September 20). National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/health-information/disorders/rett-syndrome
Sharma, N. (2009). Rett Syndrome. Encyclopedia of Neuroscience, Vol. 8, 305–307. https://doi.org/10.1016/b978-008045046-9.01498-4
Neurological Sciences
