Angelman Syndrome:

Angelman syndrome (AS) is characterized by dysmorphic facial features, microcephaly, severe mental retardation, failure to learn speech, gait ataxia, and frequent laughter. The genetic basis of the disorder is complex. The majority of patients (70%) have interstitial deletions of the maternal chromosome 15 (q11.2-q13). Approximately 7%-9% have mutations of the imprint control region, 4%-6% have point mutations in the UBE3A gene, and 3%-5% have paternal uniparental disomy (UPD). In the remaining 10%-14% of patients with AS, no molecular abnormality has been found.

The American College of Medical Genetics has described two approaches to laboratory diagnosis. The first approach, to be used in cases with a high degree of suspicion of AS, is DNA methylation analysis, which will detect AS cases caused by deletion, UPD or imprint defects. If the results are negative, chromosome analysis or UBE3A gene sequencing should be performed to rule out chromosome abnormalities, or point mutations, respectively. In the second approach, chromosome analysis and FISH are carried out first to detect AS patients with deletions and non-AS patients with chromosome abnormalities. If negative, DNA methylation studies can be performed to detect AS cases with UPD and imprint control mutations.

For Testing Methodology, Specimen Requirements and CPT codes, refer to:

Angelman Syndrome: DNA Methylation Testing

Angelman Syndrome: Uniparental Disomy Analysis

Angelman Syndrome: FISH Analysis