THE GENE THAT SILENCES CHILDHOOD: INSIGHTS INTO RETT SYNDROME

Rett syndrome (RS) is an uncommon, degenerative neurodevelopmental disorder that affects around 1 in 10,000-15,000 female children and occurs primarily as a result of mutations in the MECP2 gene on the X chromosome. Children with RS appear to develop normally until the first six to eighteen months, when they begin to regress and experience characteristic symptoms, including loss of the ability to use their hands purposefully, inability to develop spoken language, abnormal walking abilities, and stereotyped hand movement patterns. The atypical variants of RS are the result of mutations in the CDKL5 and FOXG1 genes and may present with earlier onset of seizure activity or no normal developmental period. Dysfunction of the MECP2 gene disrupts transcriptional regulation of genes involved with synaptic connectivity (how the neurons talk to each other), neuronal maturation, and the balance between excitatory and inhibitory actions on the nervous system resulting in seizure activity, impairment of movement, irregular respiratory function, dysregulation of the autonomic nervous system (which controls the automatic processes of the body), and severe cognitive impairment. Diagnosis is based upon patterns of clinical regression and is confirmed through genetic testing. Current treatment for RS is supportive and done by a team of medical professionals. Goals for supportive treatment are to provide individuals with seizure control, nutrition, physical therapy, and behavioral management. While there is no cure for RS, advances in molecular research have led to the approval of Trofinetide, and ongoing research studies using gene therapy, RNA correction, and neurotrophic modulation for RS are showing promise as disease-modifying treatments. Early diagnosis, coordination of care across the continuum of care, and the advancement of research will continue to improve the quality of life and outcomes for individuals with Rett syndrome.