Angelman and Prader-Willi Syndromes, DNA Analysis

Whole blood, LabCorp buccal swab kit (buccal swab collection kit contains instructions for use of a buccal swab), amniotic fluid or cultured amniocytes. (Cultured cells are required for testing. Direct specimen can be submitted, but a culture fee may be included.) Note: Submission of maternal blood is required for fetal testing.

7 mL whole blood, 10 mL amniotic fluid, cultured amniocytes, or LabCorp buccal swab kit

3 mL whole blood, 5 mL amniotic fluid, cultured amniocytes, or two buccal swabs

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

This test detects all major causes of the Prader-Willi and Angelman syndromes. 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 the loss of paternal gene expression in the 15q11-q13 region. 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 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.

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

This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the Food and Drug Administration.

Methylation-specific PCR and gel electrophoresis