Angelman Syndrome and Prader-Willi Syndrome by Methylation
2005077
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.
Submit With Order
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.

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





See Compliance Statement C: www.aruplab.com/CS
Statement C: The performance characteristics of this test were validated by ARUP Laboratories. The U.S. Food and Drug Administration (FDA) has not approved or cleared this test; however, FDA approval or clearance is currently not required for clinical use of this test. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions. ARUP is authorized under Clinical Laboratory Improvement Amendments (CLIA) and by all states to perform high-complexity testing.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
 
Note
 
CPT Code(s)
81331
Components
Component Test Code*Component Chart NameLOINC
2005078Angelman and Prader-Willi Specimen31208-2
2005079Angelman and Prader-Willi Result35466-2
* 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