Rett syndrome

doi:10.1038/s41572-024-00568-0

Rett syndrome

2024-11-07

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DOI：10.1038/s41572-024-00568-0

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Rett syndrome (RTT) is a severe, progressive, neurodevelopmental disorder, which affects predominantly females. In most cases, RTT is associated with pathogenic variants in MECP2. MeCP2, the protein product of MECP2, is known to regulate gene expression and is highly expressed in the brain. RTT is characterized by developmental regression of spoken language and hand use that, with hand stereotypies and impaired ambulation, constitute the four core diagnostic features. Affected individuals may present multiple other neurological impairments and comorbidities, such as seizures, breathing irregularities, anxiety and constipation. Studies employing neuroimaging, neuropathology, neurochemistry and animal models show reductions in brain size and global decreases in neuronal size, as well as alterations in multiple neurotransmitter systems. Management of RTT is mainly focused on preventing the progression of symptoms, currently improved by guidelines based on natural history studies. Animal and cellular models of MeCP2 deficiency have helped in understanding the pathophysiology of RTT and guided the development of trofinetide, an IGF1-related compound, which is an approved drug for RTT, as well as of other drugs and gene therapies currently under investigation. Rett syndrome is a rare genetic disorder affecting predominantly females resulting in severe physical and mental disability. In this Primer, Gold and colleagues review the epidemiology, mechanisms, diagnosis and treatment as well as highlight the quality of life of individuals with Rett syndrome.

Keywords:

QUALITY-OF-LIFE

CPG-BINDING PROTEIN-2

WILD-TYPE MICROGLIA

MOUSE MODEL

MECP2 MUTATIONS

DEPENDENT PHOSPHORYLATION

INTELLECTUAL DISABILITY

NEUROLOGICAL SYMPTOMS

BEHAVIORAL DEFICITS

BDNF TRANSCRIPTION

Rett syndrome

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