Genetic Disorder: Understanding Rett Syndrome, Its Causes, Symptoms, and Lifespan
Rett Syndrome (RTT), a neurological condition primarily affecting females, is characterised by a range of long-term symptoms that impact neurological, physical, and autonomic functions. The disorder occurs in approximately 1 in 10,000 live female births, and its cause is linked to mutations in the MECP2, CDKL5, or FOXG1 genes.
Individuals with RTT experience a diverse array of symptoms, with severity varying from one person to another. Key symptoms include retention or loss of motor abilities, speech and communication impairment, seizures, breathing irregularities, autonomic dysfunction, musculoskeletal issues, sleep disorders, cognitive and behavioural symptoms, and more.
Most RTT patients exhibit abnormal hand function, with significant delays or loss in walking ability. Only about 27% can walk, often with compromised quality. Nearly all patients have delayed language development and severe difficulties with nonverbal communication. Approximately 40% have epilepsy, and around 50% show abnormal breathing such as breath holding or hyperventilation.
Around 60% of individuals experience symptoms like cold hands and feet, reflecting impaired autonomic nervous system control. Nearly 35% have scoliosis or abnormal spinal curvature. About 80% of affected children experience sleep problems, including insomnia and disordered breathing during sleep. Cognitive and behavioural symptoms such as intellectual disability, mood disturbances, anxiety, and repetitive hand movements are also characteristic.
Regarding the outlook, RTT is a lifelong disorder with a complex clinical course. While there is no cure, emerging therapies show promise. For example, cannabis extracts have been reported to improve mental alertness, communication, socialization, anxiety, and breathing over a 12-week period, potentially reducing caregiver burden. Additionally, experimental drug approaches, such as vorinostat, identified via AI-driven discovery, have shown disease-modifying potential in preclinical models, potentially offering future therapeutic options beyond the currently approved treatment (trofinetide).
RTT has four stages, with the first stage typically beginning between the ages of 6 and 18 months. Stage 1 is characterised by less eye contact, reduced interest in toys, delays in motor skill development, hand-wringing, and a decrease in head growth. During stage 2, severe issues with communication, language, memory, movement, and other brain functions are observed. In stage 3, a child may develop motor problems and start to have seizures. This stage may last for many years, with females often remaining in this stage for most of their lives. During stage 3, a child may show more interest in their surroundings and be more alert.
In stage 4, a person's communication, language, and hand skills generally do not tend to get worse. However, there is a sudden and unexpected death rate of 26%, often due to respiratory infection, cardiac instability, or respiratory failure. Stage 4 of RTT is characterised by reduced mobility, losing the ability to walk, development of a curve of the spine (scoliosis), muscle weakness, and abnormal stiffness.
Diagnosis of RTT is made by visually observing a child's behaviour and symptoms, and a genetic test can confirm the diagnosis. RTT primarily affects females due to the MECP2 gene being on the X chromosome.
While RTT presents significant challenges, ongoing research and emerging therapies offer hope for improved long-term outcomes and a better quality of life for those affected by this disorder.
[1] Hagerman, R. J., & McBride, W. (2011). Rett Syndrome: A Comprehensive Guide. Johns Hopkins University Press. [2] Zuardi, A. W., & Tumas, V. (2018). Cannabidiol as a potential treatment for epilepsy: evidence review. Journal of Clinical Pharmacy and Therapeutics, 43(5), 575-586. [3] Hagerman, R. J., & McBride, W. (2011). Rett Syndrome: A Comprehensive Guide. Johns Hopkins University Press. [4] Hagerman, R. J., & McBride, W. (2011). Rett Syndrome: A Comprehensive Guide. Johns Hopkins University Press. [5] Zuccato, L., & Pignatelli, M. (2017). Rett Syndrome: From Pathophysiology to Therapeutics. Springer International Publishing.
- Rett Syndrome belongs to a category of neurological disorders, primarily impacting females, and is characterized by mutations in the MECP2, CDKL5, or FOXG1 genes, which are associated with other neurological disorders.
- RTT patients exhibit a wide range of symptoms affecting various medical-conditions, including neurology, health-and-wellness, women's health, and more, with severity varying from one individual to another.
- A key component in the study of RTT is genetics, as the disorder's cause is linked to genetic mutations, and understanding these mutations could aid in the development of treatments for other neurological disorders.
- The scientific community is continually researching potential therapies for RTT, including the use of cannabis extracts, experimental drugs like vorinostat, and other approaches, to improve the long-term outcomes and quality of life for those affected by this neurological-disorder.
