Angelman Syndrome

Angelman syndrome (AS) is characterized by severe developmental delay or intellectual disability, severe speech impairment, gait ataxia and/or tremors in the limbs. Microcephaly and seizures are common. Affected individuals also display characteristic demeanor that includes inappropriate laughing, smiling, and excitability.

There are a number of genetic changes that cause AS, although each produces a similar clinical phenotype. Approximately 70% of cases are the result of a deletion in the maternally contributed chromosome 15q11-q13 region. Approximately 5% of cases have received two copies of chromosome 15 from their father and none from their mother: paternal uniparental disomy (patUPD). Like the deletion patients, paternal UPD patients are deficient for maternally derived genes in the AS critical region. Approximately 5% of patients have an 'imprinting mutation' which alters the normal expression of maternal genes in the AS critical region. Approximately 20% of clinically diagnosed AS patients have genetic alterations other than deletion, UPD or imprinting mutations. These mutations are not detected by methodology currently in place in the Molecular Genetics Laboratory, and samples may be referred to a research lab for further investigation.

DNA in the AS critical region is methylated. If the normal expression of genes in the critical region is altered due to deletion, UPD or imprinting mutations, the methylation pattern is also changed. Testing the methylation status of genes within the critical region therefore allows these genetic alterations to be detected. For molecular analysis, the methylation status of the gene SNRPN within the AS critical region is measured. Abnormal methylation of the maternally derived gene is diagnostic of Angelman syndrome.

See related information sheet Angelman Syndrome