Angelman syndrome in Denmark. birth incidence, genetic findings, and age at diagnosis.

Angelman syndrome (AS) is a neurogenetic disorder caused by loss of expression of the maternal imprinted gene UBE3A on chromosome 15q11.2-q13. Clinical features of AS include severe intellectual disability, a happy disposition, ataxia, mandibular prognatism, and epilepsy. Our objectives were to examine the birth incidence of AS in Denmark and to characterize the size of the 15q11.2-q13 deletions with 1,000K array CGH. In addition, we analyzed genotype differences in regard to age at diagnosis and investigated the occurrence of deletions/duplications outside the 15q11.2-q13 regions. We identified 51 patients with genetically verified AS, which corresponded to a birth incidence of 1:24,580 (95%CI: 1:23,727-1:25,433). Thirty-six patients showed a deletion; 13 had a Class I deletion and 20 had a Class II deletion. There was bimodal distribution of the BP3 breakpoint. Three patients had larger and atypical deletions, with distal breakpoints telomeric to BP3. Five patients had paternal uniparental disomy (pUPD) of chromosome 15, and four had a verified UBE3A mutation. Additional deletions/duplications outside the 15q11.2-q13 areas were demonstrated in half the participants. Six harbored more than one CNV. Mean age at diagnosis was 21 months (95%CI: 17-23 months) for children with a deletion and 46 months (95%CI: 36-55 months) for children with pUPD or a UBE3A mutation (P < 0.01). The presence of a CNV outside 15q11.2-q13 did not have an impact on age at diagnosis.

Examining associations between early adverse life events and health anxiety using the DanFund study.

Childhood adverse life events, in particular illness-related events, have been proposed as a risk factor for development of health anxiety. OBJECTIVE: To examine: 1) The association between accumulated early adverse life events and health anxiety in adulthood and 2) The influence of specific types of life events, i.e., illness, injury, loss, and the impact of their exposure time on health anxiety in adulthood. METHOD: A population-based, cross-sectional study including 7454 participants from the Danish study of Functional Disorders (DanFunD). Health anxiety was assessed with Whiteley-6-R and early adverse life events with the Cumulative Lifetime Adversity Measure. Caseness was defined as a Whiteley-6-R score ≥ 90%ile. Generalised linear models were used to estimate the association with relative risk (RRa, adjusted for sociodemographics). RESULTS: A cumulative effect was found for each additional adverse life event with 8.03% increased risk of health anxiety. Two categories were associated with a higher risk: violence (RRa = 1.65, 95% CI: 1.37-1.99, P < 0.001) and relationship stress (RRa = 1.34; 95% CI: 1.15-1.57, P < 0.001). Respondents with self-reported childhood illness were also more likely to report health anxiety (RRa = 1.52, 95% CI 1.11-2.09, P = 0.009). Timewise, health anxiety seemed associated with illness during school age and injury during adolescence. CONCLUSIONS: Accumulated adverse life events, early exposure to specific categories and specific health-related life events were associated with self-reported health anxiety in adulthood. Our findings provide new knowledge on the potential role of early life events in health anxiety which could inform early intervention.

Neurodevelopmental outcome in Angelman syndrome: genotype-phenotype correlations.

Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability, developmental delay, lack of speech, and epileptic seizures. Previous studies have indicated that children with AS due to 15q11.2-q13 deletions have a more severe developmental delay and present more often autistic features than those with AS caused by other genetic etiologies. The present study investigated the neurodevelopmental profiles of the different genetic etiologies of AS, and examined the evolution of mental development and autistic features over a 12-year period in children with a 15q11.2-q13 deletion. This study included 42 children with AS. Twelve had a Class I deletion, 18 had Class II deletions, three showed atypical large deletions, five had paternal uniparental disomy (pUPD) and four had UBE3A mutations. Children with a deletion (Class I and Class II) showed significantly reduced developmental age in terms of visual perception, receptive language, and expressive language when compared to those with a UBE3A mutation and pUPD. Within all subgroups, expressive language performance was significantly reduced when compared to the receptive performance. A follow-up study of seven AS cases with 15q11.2-q13 deletions revealed that over 12 years, the level of autistic features did not change, but both receptive and expressive language skills improved.