From the Guidelines
Congenital Rett Syndrome, also known as Classic Rett Syndrome (RTT), is a genetic neurodevelopmental disorder caused by mutations in the MeCP2 gene, characterized by normal development at birth, followed by decelerated head growth, loss of purposeful hand movements, and development of stereotyped hand movements, typically before 4 years of age. This condition is distinct from other neurodevelopmental disorders, such as autism spectrum disorder, childhood disintegrative disorder, and Asperger's disorder, which have different clinical features and outcomes 1. The clinical manifestations of Rett syndrome can vary, but the central role of MeCP2 mutations makes it clear that boys may carry the same mutations, although with differing clinical manifestations, ranging from fatal encephalopathy to progressive but nonfatal developmental disorder 1. Key characteristics of Classic Rett Syndrome include:
- Normal development at birth and during infancy
- Decelerated head growth before 4 years of age
- Loss of purposeful hand movements
- Development of stereotyped hand movements, such as wringing or washing
- Mutations in the MeCP2 gene as the primary cause The diagnosis and management of Rett syndrome require a multidisciplinary approach, focusing on symptom management and improving quality of life, as there is no cure for the condition 1.
From the Research
Definition and Characteristics of Congenital Rett Syndrome
- Congenital Rett Syndrome, also known as Classic Rett Syndrome (RTT), is a severe neurodevelopmental disorder that primarily affects females, with an incidence of 1:10,000-20,000 female births 2, 3.
- It is characterized by an initial period of apparently normal development, followed by a rapid decline with regression of acquired motor skills, loss of spoken language and purposeful hand use, onset of hand stereotypes, abnormal gait, and growth failure 2, 3, 4.
- The disease has a characteristic developmental regression resulting in impairment of expressive language, hand skills, and ambulation that is accompanied by hand stereotypies 5.
Genetic Causes
- Mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2) are associated with most cases of classic RTT, accounting for 95% of typical RTT cases and 73.2% of atypical RTT 2, 3, 4.
- Other genes, such as cyclin-dependent kinase like 5 (CDKL5) and FoxG1, have been identified as causative genes in atypical forms of RTT, including the congenital variant 2, 3.
Clinical Features and Management
- The course of the disease is characterized by four stages, with three different atypical variants of the disease defined 3.
- Epilepsy is a common comorbidity, reported in 60%-80% of patients with RTT, and its severity is an important contributor to the clinical severity of the disease 3.
- Management of RTT is mainly symptomatic and individualized, focusing on optimizing each patient's abilities and preventing the progression of symptoms 2, 4.