The Diagnosis of Rett Syndrome

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

  1. Developmental Regression (Defining Feature):
     • Loss of acquired purposeful hand use and spoken language.
     • Onset typically after 6–18 months of normal development.
  2. Dynamic Course:
     • Periods of regression followed by stabilization or partial recovery.
  3. Neurological Features:
     • Hand stereotypies (e.g., wringing, mouthing).
     • Gait abnormalities (e.g., ataxia, dyspraxia).
     • Seizures: High prevalence but variable severity.
  4. Behavioral Features:
     • Initial autism-like behaviors, followed by anxiety and mood instability.
     • Inappropriate laughing/screaming (supportive diagnostic criterion).
  5. 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

  1. 1985 Criteria:
     • Introduced inclusion and exclusion criteria.
     • Emphasis on female predominance and regression of language and hand use.
  2. 1988 Criteria:
     • Included supportive criteria to assist diagnosis.
  3. 2002 Revision:
     • Acknowledged MECP2 mutations and recognized atypical RTT.
  4. 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.

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