Rett Syndrome (MECP2), Sequencing and Deletion/Duplication

Background Information
Characteristics: Classic Rett Syndrome is a progressive neurodevelopmental disorder characterized by normal development until 6-18 months of age followed by rapid developmental regression, deceleration of head growth, loss of speech and acquired motor skills, and seizures; purposeful use of the hands is replaced by repetitive stereotyped hand movements. MECP2-related disorders include Rett-like Syndrome, severe congenital encephalopathy, or mild to severe mental retardation.
Incidence: 1 in 10,000.
Inheritance: X-linked dominant; most cases are sporadic.
Cause: Methyl-CpG-Binding Protein 2 (MECP2) gene mutations.
Clinical Sensitivity: Up to 95 percent.
Methodology: Bidirectional sequencing of the MECP2 coding regions (exons 1-4) and intron-exon boundaries; Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large deletions/duplications in the MECP2 coding regions (exons 1-4).
Analytical Sensitivity: 99 percent for sequencing and 90 percent for MLPA.
Analytic Specificity: 99 percent for sequencing and 98 percent for MLPA. 
Limitations: Breakpoints of large deletions/duplications cannot be determined; deep intronic mutations will not be detected. Diagnostic errors can occur due to rare sequence variations.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.