Angelman syndrome (AS, OMIM ref. 105830) is characterised by severe developmental delay, absent or severely limited speech, gait ataxia and/or tremulousness of the limbs, and a unique behavior with a happy demeanor that includes frequent and sometimes inappropriate laughter, smiling, and excitability. In addition, microcephaly and seizures are common. Affected individuals usually have a characteristic electroencephalography (EEG) appearance with striking high voltage activity. Developmental delay is first noted at around six months of age; however, the unique clinical features of AS may not manifest until after one year of age, and it can take several years before the correct clinical diagnosis is obvious. The diagnosis of AS rests upon a combination of clinical features as well as molecular genetic testing and/or cytogenetic analysis. Consensus clinical diagnostic criteria for AS have been developed. Angelman syndrome (AS) has a prevalence of~1/12,000. Loss of the maternally contributed AS region can occur by five genetic mechanisms: deletion (70-75% of cases), paternal uniparental disomy of chromosome 15 (3-7% of cases), imprinting defects (2-3% of cases), mutation of the ubiquitin-protein ligase (UBE3A) gene (~10% of cases) or unidentified mechanisms (Ramsden et al, 2010, BMC Med. Genet., 11:70).
We accept referrals of patients with appropriate signs and symptoms for a differential diagnosis of AS. An expert clinical review is required for referral for UBE3A mutation scanning.
A methylation sensitive PCR (SNRPN) test is used to detect an abnormal pattern of methylation within the 15q11-q13 region. As 20% of AS cases would not be detected by this method, this result does not exclude the diagnosis. In cases where clinical suspicion remains strong, mutation scanning in UBE3A may be indicated. This is performed using bidirectional sequencing of the functional coding sequence of the gene and UBE3A MLPA.
Price & reporting times
NHS referrals to this service are paid for where there is an existing specialist commissioning contract for genetic testing. In other cases please contact the lab for prices.
Price (non- NHS)
|TRT (Calendar days)|
|Methylation sensitive (SNRPN) PCR||POA||POA||28|
|UBE3A mutation scanning||POA||POA||56|
|UBE3A single mutation test||POA||POA||28|
Test validation & quality assurance - information for users
~80% of AS cases (those due to a deletion, paternal UPD or an imprinting mutation) are detected by the methylation sensitive (SNRPN) PCR test. A further 10% of cases with key features of AS are detected by UBE3A mutation scanning.
4ml EDTA blood sample
Please see our referral guidelines for more information.
OMIM Number(s) - 105830
Gene(s) - (testing may involve SNRPN, UBE3A)