Genetic Instability and Disease Progression of Indian Rett Syndrome Patients

Area of Science:

• Neuroscience
• Genetics
• Biochemistry

Background:

• Rett syndrome (RTT) is a rare neurodevelopmental disorder affecting 1 in 10,000 individuals worldwide.
• It is caused by mutations in the methyl CpG binding protein 2 (MECP2) gene, leading to hallmark symptoms like developmental delay, microcephaly, and seizures.
• Understanding RTT diagnosis and clinical manifestations among healthcare professionals requires further investigation.

Purpose of the Study:

• To investigate the clinical manifestations and MECP2 genetic heterogeneity in South Indian RTT patients.
• To correlate biochemical findings with RTT subtypes and clinical severity.
• To enhance early diagnosis and prognosis of RTT by identifying key biomarkers.

Main Methods:

• Screened 208 autistic patients, diagnosing 20 with RTT (11 classical, 9 variant).
• Assessed clinical severity using RSSS, RSBQ, SSI, SSS, and RTT gross motor scale.
• Performed biochemical analysis (TSH, dopamine, cholesterol, blood pressure, calcium, ferritin, HDL) and MECP2 gene sequencing.

Main Results:

• Classical RTT (Group I) showed higher TSH, dopamine, and cholesterol levels compared to variant RTT (Group II).
• Blood pressure, calcium, ferritin, and HDL levels were significantly decreased in both RTT groups versus controls.
• MECP2 mutations were identified in 12/20 patients (60% pathogenic, 20% unknown), correlating with respiratory dysfunction, scoliosis, and sleep issues.

Conclusions:

• Significant clinical and genetic differences exist between classical and variant RTT in the South Indian population.
• Biochemical markers like cholesterol, calcium, and TSH levels, alongside MECP2 mutations, are crucial for early RTT diagnosis and prognosis.
• This study provides valuable insights for clinicians to improve RTT patient management and early intervention strategies.