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

Fetal Specimen: Four (4) T-25 flasks at 80 percent confluency of cultured amniocytes. If the client is unable to culture amniocytes, this can be arranged by contacting ARUP Client Services at (800) 522-2787. Or amniotic fluid. 
AND Maternal Specimen
: Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).

Specimen Preparation

Cultured Amniocytes: Fill flasks with culture media. Transport four (4) T-25 flasks at 80 percent confluency of cultured amniocytes. Backup cultures must be retained at the client's institution until testing is complete.
OR Amniotic Fluid
: Transport 20 mL unspun fluid. (Min: 10 mL)
AND Maternal Specimen
: Transport 3 mL whole blood. (Min: 1 mL)

Storage/Transport Temperature

Cultured Amniocytes: CRITICAL ROOM TEMPERATURE. Must be received within 48 hours of shipment due to liability of cells.
Amniotic Fluid
: Room temperature.
Maternal Specimen
: Room temperature.

Unacceptable Conditions
Remarks

Maternal specimen is recommended for proper test interpretation. Order Maternal Cell Contamination, Maternal Specimen. This can be arranged by contacting ARUP genetic counselors at (800) 242-2787 ext. 2141. Patient History Form is available on the ARUP Web site or by contacting ARUP Client Services.

Stability

Fetal Specimen: Ambient: 48 hours; Refrigerated: Unacceptable; Frozen: Unacceptable
Maternal Specimen
: Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable

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.

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