ARUP's Laboratory Test Directory

Angelman Syndrome and Prader-Willi Syndrome by Methylation : 2005077
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Additional Technical Information


Mnemonic: AS PWS

Ordering Recommendation: Diagnostic testing for Angelman syndrome or Prader-Willi syndrome.
Methodology: Methylation Sensitive Polymerase Chain Reaction/Fluorescence Monitoring
Performed: Mon, Thu
Reported: 7-10 days
Specimen Required: Collect: Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).

Specimen Preparation: Transport 3 mL whole blood. (Min: 1.5 mL)

Storage/Transport Temperature: Refrigerated.

Stability (collection to initiation of testing): Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Reference Interval:
By report
Interpretive Data: 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: Bisulfite conversion and PCR amplification to detect methylation using melting curve analysis.
Limitations: Molecular mechanisms not affecting methylation patterns that may result in AS will not be assessed.

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: Bisulfite conversion and PCR amplification to detect methylation using melting curve analysis.
Limitations: Molecular mechanisms not affecting methylation patterns that may result in PWS will not be assessed.

This test is performed pursuant to an agreement with Roche Molecular Systems, Inc.



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

See Compliance Statement C: www.aruplab.com/CS
CPT Code(s): 81331
Cross References: Prader-Labhart-Willi Syndrome (Angelman Syndrome and Prader-Willi Syndrome by Methylation), Prader-Willi Syndrome (Angelman Syndrome and Prader-Willi Syndrome by Methylation)