Manifestations in institutionalised adults with Angelman syndrome due to deletion

Abstract

Undiagnosed institutionalised patients were reviewed in an attempt to identify those with Angelman syndrome (AS). The aim was to test these patients for deletion of chromosome 15(q11-13) and to describe the adult phenotype. The selection criteria included severe intellectual disability, ataxic or hypermotoric limb movements, lack of speech, a "happy" demeanour, epilepsy, and facial appearance consistent with the diagnosis. Patients were examined, medical records perused, and patients' doctors contacted as required. Genetic tests performed included routine cytogenetics, DNA methylation analysis (with probe PW71B), and fluorescence in situ hybridisation (with probes D15S10, GABRbeta3, or SNRPN). A deletion in the AS region was detected in 11 patients (9 males and 2 females) of 22 tested. The mean age at last review (March 1996) was 31.5 years (range 24 to 36 years). Clinical assessment documented findings of large mouth and jaw with deep set eyes, and microcephaly in nine patients (two having a large head size for height). No patient was hypopigmented; 1/11 patients was fair. Outbursts of laughter occurred in all patients but infrequently in 7/11 (64%) and a constant happy demeanour was present in 5/11 (46%). All had epilepsy, with improvement in 5/11 (46%), no change in 4 (36%), and deterioration in 2 (18%). The EEG was abnormal in 10/10 patients. Ocular abnormalities were reported in 3/8 patients (37.5%) and 4/11 (36%) had developed kyphosis. Two had never walked. All nine who walked were ataxic with an awkward, clumsy, heavy, and/or lilting gait. No patient had a single word of speech but one patient could use sign language for two needs (food and drink). Our data support the concept that AS resulting from deletion is a severe neurological syndrome in adulthood. The diagnosis in adults may not be straightforward as some manifestations change with age. Kyphosis and keratoconus are two problems of older patients.

Parental view of epilepsy in Angelman syndrome: a questionnaire study

“…The most frequent type of seizures in previous studies on Angelman syndrome were tonic-clonic seizures, atypical absence seizures, myoclonic seizures, tonic seizures, and status epilepticus in childhood; absence status and myoclonic status epilepticus were also found 10-25. In adulthood, atypical absence seizures, myoclonic seizures, or a combination of the two are the most prominent,31 32 as was reported in our four adult patients with Angelman syndrome.…”

“…Furthermore, the four patients older than 20 years in our series were reported not to be free from fits. A few previous studies reported that seizures reduce in Angelman syndrome with age10 11 and are more easily controlled in later childhood,21 22 but more recent, larger surveys24 31 32 have found that 92% of the adult patients with Angelman syndrome continue to have epileptic seizures and that seizures play an important role in daily life.…”

Angelman syndrome: evolution of the phenotype in adolescents and adults

“…There have been several good clinical reviews of AS (Williams and Frias 1982, Robb et al 1989, Zori et al 1992, Clayton-Smith 1993 but these have concentrated mainly on the clinical features in younger patients. Bjerre reported a 76-year-old patient from Sweden in 1984 and more recently others have published further clinical details of adults with AS (Williams et al 1989, Buntinx et al 1995, Reish et al 1995, Laan et al 1996, Sandanam et al 1997. Some reports have been of single patients and the majority have concerned adults who have lived for a great part of their life in large institutions.…”

The Lessons from Angelman Syndrome for Research and Management

“…The contribution of EEG to diagnosis of Angelman syndrome has been recognized in both children (Boyd et al, 1988;Korff et al, 2005;Rubin et al, 1997) and adults (Sandanam et al, 1997;Van Buggenhout et al, 2000), and particularly highlighted in infants (Van Lierde et al, 1990). In contrast to the paucity of physiologic rhythms, interictal EEG shows three distinctive high-amplitude rhythmic patterns (Dan & Boyd, 2003), which can reinforce the clinical diagnosis (Williams et al, 2006).…”