Ordering Recommendation

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

Methodology

Qualitative /Methylation-Specific Multiplex Ligation-Dependent Probe Amplification (MS-MLPA)

Performed

Varies

Reported

12-14 days
If culture is required, an additional 1 to 2 weeks is required for processing time.

New York DOH Approval Status

Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.

Specimen Required

Patient Preparation
Collect

For Nonfetal Specimens: Lavender (EDTA), pink (K2EDTA), or yellow (ACD solution A) For Fetal Specimens: Two T-25 flasks at 80 percent confluent of cultured amniocytes AND Maternal Whole Blood Specimen: Lavender (EDTA), pink (K2EDTA), or yellow (ACD solution A) Fetal Specimens will require MCC-FETAL testing to be added on by ARUP, and additional charges will apply.

Specimen Preparation

For Nonfetal Specimens: Transport 3 mL whole blood (Min: 1mL) For Fetal Specimens: Cultured Amniocytes: Fill flasks with culture media. Transport two T-25 flasks at 80 percent confluent of cultured amniocytes filled with culture media. Backup cultures must be retained at the client's institution until testing is complete. If ARUP receives a sample below the minimum confluence, CG GRW&SND (0040182) will be added on by ARUP, and additional charges will apply. If clients are unable to culture specimens, CG GRW&SND should be added to initial order. Maternal Whole Blood Specimen: Transport 3 mL whole blood (Min: 1 mL)

Storage/Transport Temperature

For Nonfetal Specimens: Whole Blood: Refrigerated. Also acceptable: Ambient. For Fetal Specimens: Cultured Amniocytes: CRITICAL ROOM TEMPERATURE. Must be received within 48 hours of shipment due to viability Maternal Whole Blood Specimen: Refrigerated. Also acceptable: Ambient.

Unacceptable Conditions

For Nonfetal Specimens: Transfused whole blood, severely hemolyzed whole blood, heparinized whole blood, frozen whole blood.

Remarks
Stability

For Nonfetal Specimens: Whole Blood: Room temperature: 1 week; Refrigerated: 1 month; Frozen: unacceptable. For Fetal Specimens: Cultured Amniocytes: Room temperature: 48 hours; Refrigerated: Unacceptable; Frozen: Unacceptable Maternal Whole Blood Specimen: Room temperature: 1 week; Refrigerated: 1 month; Frozen: Unacceptable.

Reference Interval

Interpretive Data

BACKGROUND INFORMATION: Angleman Syndrome and Prader-Willi Syndrome by Methylation-Specific MLPA

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.
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 for AS; 1 in 15,000 for PWS.
Inheritance: Varies, depending on the molecular genetic mechanism.
Cause: AS: Absence of maternal expression of the UBE3A gene. PWS: Absence of the paternally contributed PWS/AS critical region of chromosome 15q11.2-q13.
Molecular Genetic Mechanisms: AS: 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). PWS: 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: PWS: Over 99 percent. AS: 80 percent.
Methodology: Methylation-specific multiplex ligation probe amplification (MLPA) of the AS/PWS critical region of chromosome 15q11.2-q13.
Analytical Sensitivity and Specificity: 99 percent for AS and PWS.
Limitations: Disease mechanisms causing AS that do not alter methylation patterns will not be detected. Diagnostic errors can occur due to rare sequence variations. This assay is not validated to detect increased copy number of 15q11.2-q13 nor determine parent of origin for duplications. This assay cannot distinguish between uniparental disomy (UPD) or an imprinting defect for PWS or AS. AS and PWS mosaicism will not be assessed by this assay. Interpretation of this test result may be impacted if this patient has had an allogeneic stem cell transplantation. Methylation patterns may not be fully established in early gestation; thus, diagnostic testing on chorionic villus samples is not recommended.

This test was developed and its performance characteristics determined by ARUP Laboratories. It has not been cleared or approved by the U.S. 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; for fetal specimens add 81265

Components

Component Test Code* Component Chart Name LOINC
3006248 AS-PWS Specimen 66746-9
3006249 AS-PWS Interpretation 41117-3
* 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-Specific MLPA