Angelman Syndrome and Prader-Willi Syndrome by Methylation-Sensitive PCR

Background information: Angelman Syndrome and Prader-Willi Syndrome by Methylation:

Characteristics of Angelman Syndrome (AS): Developmental delays by 6-12 months of age, seizures, microcephaly, movement or balance disorder, minimal or absent speech, and a distinctive behavioral phenotype, which includes a happy demeanor with frequent laughter, hand flapping, and excitability.
Prevalence: 1 in 15,000.
Inheritance: Varies, depending on the molecular genetic mechanism.
Cause: Absence of maternal expression of the UBE3A gene. 
Molecular Genetic Mechanisms: Microdeletions in the AS/PWS critical region (68 percent), UBE3A mutations (11 percent), paternal uniparental disomy of chromosome 15 (7 percent), imprinting center defects (3 percent), unbalanced chromosome translocation (less than 1 percent), and unknown (10 percent).
Clinical Sensitivity: 78 percent.
Analytical Sensitivity and Specificity: 99 percent.
Methodology: Methylation Sensitive Polymerase Chain Reaction/Fluorescence Monitoring.
Limitations: Molecular mechanisms not affecting methylation patterns that may result in AS will not be assessed. Diagnostic errors can occur due to rare sequence variations.

Characteristics of Prader-Willi Syndrome (PWS): Neonatal hypotonia, hyperphagia, obesity, global developmental delay, mild intellectual disability, hypogonadism, and a distinctive behavioral phenotype, which includes temper tantrums, stubbornness, manipulative behavior, and obsessive-compulsive behavior.
Prevalence: 1 in 15,000.
Inheritance: Varies, depending on the molecular genetic mechanism.
Cause: Absence of the paternally contributed PWS/AS critical region of chromosome 15q11.2-q13.
Molecular Genetic Mechanisms: Microdeletions in the PWS/AS critical region (70-75 percent), maternal uniparental disomy of chromosome 15 (25-29 percent), imprinting center defect or balanced chromosome translocation (less than 1 percent).
Clinical Sensitivity: Over 99 percent.
Analytical Sensitivity and Specificity: 99 percent.
Methodology: Methylation Sensitive Polymerase Chain Reaction/Fluorescence Monitoring.
Limitations: Molecular mechanisms not affecting methylation patterns that may result in PWS will not be assessed. Diagnostic errors can occur due to rare sequence variations.

This test was developed and its performance characteristics determined by ARUP Laboratories. It has not been cleared or approved by the US Food and Drug Administration. This test was performed in a CLIA certified laboratory and is intended for clinical purposes.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.