The Diagnosis of Rett Syndrome (RTT)
Introduction
- Definition: Rett Syndrome (RTT) is a rare neurodevelopmental disorder, primarily affecting females, characterized by developmental regression, loss of acquired skills, and stereotypic hand movements.
- Historical Milestones:
- 1966: First described by Dr. Andreas Rett.
- 1999: Association with mutations in the MECP2 gene (Amir et al.).
Overview of Clinical Features
- Developmental Regression (Defining Feature):
- Loss of acquired purposeful hand use and spoken language.
- Onset typically after 6–18 months of normal development.
- Dynamic Course:
- Periods of regression followed by stabilization or partial recovery.
- Neurological Features:
- Hand stereotypies (e.g., wringing, mouthing).
- Gait abnormalities (e.g., ataxia, dyspraxia).
- Seizures: High prevalence but variable severity.
- Behavioral Features:
- Initial autism-like behaviors, followed by anxiety and mood instability.
- Inappropriate laughing/screaming (supportive diagnostic criterion).
- Systemic Features:
- Orthopedic: Scoliosis, kyphosis, contractures.
- Growth abnormalities: Deceleration in head growth, small hands and feet.
- Cardiac: Prolonged QT interval.
- Other: Osteopenia, gastrointestinal issues.
Evolution of Diagnostic Criteria
- 1985 Criteria:
- Introduced inclusion and exclusion criteria.
- Emphasis on female predominance and regression of language and hand use.
- 1988 Criteria:
- Included supportive criteria to assist diagnosis.
- 2002 Revision:
- Acknowledged MECP2 mutations and recognized atypical RTT.
- 2010 Criteria (Current):
- Simplified framework validated on a large cohort.
- Introduced two clinical forms:
- Typical RTT: Requires all core features.
- Atypical RTT: Requires at least two core features and five supportive criteria.