Icon

Consent Form Recommended
Ordering Recommendation

Preferred initial diagnostic test for Angelman syndrome or Prader-Willi syndrome.

Mnemonic
AS PWS
Methodology

Methylation Sensitive Polymerase Chain Reaction/Fluorescence Monitoring

Performed

Mon, Thu

Reported

7-10 days

New York DOH Approval Status
This test is New York DOH approved.
Specimen Required
Patient Preparation
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.

Unacceptable Conditions
Remarks
Stability

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. 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: 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. Diagnostic errors can occur due to rare sequence variations.

Compliance Category

Laboratory Developed Test (LDT)

Note
Hotline History
N/A
CPT Codes

81331

Components
Component Test Code* Component Chart Name LOINC
2005078 Angelman and Prader-Willi Specimen 31208-2
2005079 Angelman and Prader-Willi Result 35466-2
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • Prader-Labhart-Willi Syndrome
Angelman Syndrome and Prader-Willi Syndrome by Methylation-Sensitive PCR