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Angelman/Prader-Willi Syndromes Methylation Assay

CPT:

81331

Angelman syndrome (AS) is characterized by severe developmental delay/intellectual disability, absence of speech, ataxic gait, inappropriate laughter, hand-flapping, and less frequently, microcephaly and seizures. Indications for testing include: clinical characteristics of AS or pregnancies at risk due to a known translocation or imprinting mutation. AS is not usually suspected in the first year of life, but becomes a consideration between 1-4 years of age.

Prader-Willi syndrome (PWS) is characterized by: hypotonia, failure to thrive in infancy, rapid weight gain/obesity between 12 months and 6 years, characteristic facial features, hypogonadism and mild to moderate intellectual disability. Indications for testing include clinical characteristics of PWS or pregnancies at risk due to a known translocation or imprinting mutation.

Test Details

Use

This test detects all major causes of the Prader-Willi and Angelman syndrome

Synonyms

Prader-Willi and Angelman Syndromes, DNA Analysis; PWS Methylation Assay;

Test Includes

This assay detects all cases of AS and PWS arising from UPD, microdeletions and imprinting defects, but does not define the nature of underlying genetic defect. UBE3A mutations that cause AS are not detected by this assay.

Methodology

Methylation-specific PCR and gel electrophoresis

Pregnancy Week

14–21 Weeks
22+ Weeks

Specimen Requirements

Volume

7 mL whole blood; 10 mL amniotic fluid; or LabCorp buccal swab kit

Minimum Volume

3 mL whole blood; 5 mL amniotic fluid; or two buccal swabs

Container

Lavender-top (EDTA) tube, yellow-top (ACD) tube, sterile plastic conical tube or two confluent T25 flasks for fetal testing, or LabCorp buccal swab kit

Special Instructions

Please provide pertinent findings (family or personal) of intellectual disability, autistic behaviors, developmental delay, or obesity. It is recommended that in addition to this methylation-based testing, High-resolution Chromosome Analysis be ordered (052215) to distinguish between the underlying mechanisms.

Causes for Rejection

Frozen specimen; hemolysis; quantity not sufficient for analysis; improper container; one buccal swab; wet buccal swab

Storage Instructions

Maintain specimen at room temperature or refrigerate. Do not freeze.

Additional Information

Angelman syndrome (AS) (OMIM 105830) is characterized by severe developmental delay or intellectual disability, severe speech impairment, gait ataxia and/or jerking limb motions, and an inappropriate happy demeanor that includes frequent laughing, smiling, and excitability. Neonatal hypotonicity may also occur. Approximately 70% of AS patients have a deletion of 15q11-13 in the maternally-contributed chromosome 15, with about 3% to 5% of AS cases resulting from paternal uniparental disomy (UPD). Approximately 11% of AS cases result from mutations in the maternal copy of the UBE3A gene that also maps to 15q11-13. An abnormality of the imprinting process occurs in a portion of the remaining patients. Prader-Willi syndrome (PWS) (OMIM 176270) is caused by an abscess of paternal SNRPN gene expression. The disease is characterized by diminished fetal activity, severe postnatal hypotonia, failure to thrive in infancy followed by hyperphagia, obesity, developmental delay, and hypogonadism. PWS may result from a microdeletion of the paternal chromosome at 15q11-13 (70%), maternal UPD (25%), or from an imprinting defect. Imprinting defects may be associated with a 50% recurrence risk, however, the risk is negligible for cases involving microdeletions or UPD. Consequently, etiological testing may be indicated. All test results must be combined with clinical information for the most accurate interpretation.

Limitations

Approximately 11% of Angelman syndrome cases arising from UBE3A mutations will not be detected by this test.

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