Ordering Recommendation

Prenatal testing for Angelman syndrome or Prader-Willi syndrome. Use to identify cases resulting from molecular mechanisms that produce abnormal methylation patterns.

Mnemonic

AS PWS FE

Methodology

Methylation Sensitive Polymerase Chain Reaction/Fluorescence Monitoring

Performed

Mon, Thu

Reported

2-7 days

New York DOH Approval Status

This test is New York DOH approved.

Specimen Required

Patient Preparation
Collect

Contact ARUP's genetic counselors at (800) 242-2787 extension 2141 prior to submission for specimen requirements and submission information.

Specimen Preparation
Storage/Transport Temperature
Unacceptable Conditions
Remarks
Stability

Reference Interval

By report

Interpretive Data

Background information: Angelman Syndrome and Prader-Willi Syndrome by Methylation, Fetal:
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.

For quality assurance purposes, ARUP Laboratories will confirm the above result at no charge following delivery. Order Confirmation of Fetal Testing and include a copy of the original fetal report (or the mother's name and date of birth) with the test submission. Please contact an ARUP genetic counselor at (800) 242-2787 extension 2141 prior to specimen submission.

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.

Compliance Category

Laboratory Developed Test (LDT)

Note

Hotline History

N/A

CPT Codes

81331; 81265 Fetal Cell Contamination (FCC)

Components

Component Test Code* Component Chart Name LOINC
0050548 Maternal Contamination Study Fetal Spec 59266-7
0050612 Maternal Contam Study, Maternal Spec 31208-2
2005079 Angelman and Prader-Willi Result 35466-2
2012226 Angelman and Prader-Willi Fetal Specimen 31208-2
* 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

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