[Rett syndrome: a diagnostic, clinical and molecular update]

Area of Science:

• Genetics
• Neuroscience
• Developmental Biology

Context:

• Rett syndrome (RS) is a significant cause of intellectual disability in females.
• First described in 1966, its association with MECP2 gene mutations was identified in 1999.
• Over 500 articles published in the last 5 years underscore the complexity of RS.

Purpose:

• To provide an updated summary of Rett syndrome in Spanish.
• To consolidate current knowledge on the genetic basis and clinical manifestations of RS.
• To review recent advancements in understanding MECP2 gene function and its role in neurodevelopment.

Summary:

• RS is a dominant X-linked disorder affecting psychomotor development, characterized by autism, hand stereotypies, language loss, and microcephaly.
• Mutations in the MECP2 gene, encoding a transcriptional regulator, lead to a spectrum of phenotypes beyond the classic RS.
• Prevalence is estimated at 1/15,000 girls in Europe; over 99% of cases involve de novo mutations.
• CDKL5 gene mutations are identified in RS variants with early-onset epilepsy.

Impact:

• Advances in understanding MECP2 and CDKL5 function are crucial for diagnosing and potentially treating RS.
• Molecular studies reveal the intricate genetic architecture of neurodevelopmental disorders.
• This review emphasizes the ongoing need for research into the complex mechanisms underlying RS and related conditions.