Angelman Syndrome: Methylation Analysis

Test Information

This test determines the level of methylation at CpG sites within the Angelman syndrome/Prader-Willi syndrome critical region on chromosome 15 via pyrosequencing.

Turnaround Time

3 weeks

CPT Code(s)




Clinical Information

Prader-Willi and Angelman syndromes are examples of disorders involving imprinted genes. Imprinted genes are only expressed from either the maternally or paternally derived member of a homologous chromosome pair. Prader-Willi syndrome is characterized by significant infantile hypotonia and feeding difficulties. In early childhood this transitions into excessive eating and morbid obesity. Developmental delay and behavioral problems are common features. Physical characteristics include hypogonadism, short stature, small hands and feet, almond shaped eyes, and hypopigmentation. Prader-Willi syndrome is caused by the lack of expression of the paternally derived region of chromosome 15 (15q11.2-q13). This lack of expression can be caused by a deletion of the paternal chromosome, maternal uniparental disomy (UPD) of chromosome 15 or more rarely, a defect in the imprinting region. Angelman syndrome is characterized by significant developmental delay or intellectual disability, severe speech impairment, an ataxic gait, and inappropriate happy behavior including excessive laughing and smiling. Other physical concerns include microcephaly, seizures, wide mouth and a prominent mandible. Angelman syndrome is caused by the lack of expression of the maternally inherited region of chromosome 15 (15q11.2-q13). This lack of expression can be caused by a deletion of the maternal chromosome, paternal uniparental disomy (UPD), a mutation in the UBE3 gene in this region, or an imprinting defect.


Methylation testing is useful to confirm the diagnosis. Further testing is necessary to determine the etiology of the disorder and to allow for carrier testing and prenatal diagnosis.


Methylation analysis via pyrosequencing


Methylation analysis for Prader-Willi/Angelman syndromes will detect nearly all cases of Prader-Willi syndrome and approximately 78% of patients with Angelman syndrome.

Specimen Requirements

The preferred sample type is peripheral blood collected in an EDTA (purple top) tube – at least 2-3ml for pediatric patients and 5-6ml for adult patients. Extracted DNA is also accepted for this test.

Transport Instructions

The specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.

Prenatal Testing Information

Prenatal diagnosis is available if the familial mutations are known. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.

Have Questions? Need Support?

Call our laboratory at 1-800-473-9411 or contact one of our Laboratory Genetic Counselors for assistance.
Robin Fletcher, MS, CGC
Falecia Thomas, MS, CGC

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