Measuring What Matters to Individuals with Angelman Syndrome and Their Families: Development of a Patient-Centered Disease Concept Model.

Angelman syndrome (AS) is a complex, heterogeneous, and life-long neurodevelopmental disorder. Despite the considerable impact on individuals and caregivers, no disease-modifying treatments are available. To support holistic clinical management and the development of AS-specific outcome measures for clinical studies, we conducted primary and secondary research identifying the impact of symptoms on individuals with AS and their unmet need. This qualitative research adopted a rigorous step-wise approach, aggregating information from published literature, then evaluating it via disease concept elicitation interviews with clinical experts and caregivers. We found that the AS-defining concepts most relevant for treatment included: impaired expressive communication, seizures, maladaptive behavior, cognitive impairment, motor function difficulties, sleep disturbance, and limited self-care abilities. We highlight the relevance of age in experiencing these key AS concepts, and the difference between the perceptions of clinicians and caregivers towards the syndrome. Finally, we outline the impact of AS on individuals, caregivers, and families.

Clinical Characterization of Epilepsy in Children With Angelman Syndrome.

BACKGROUND: Epilepsy is highly prevalent in children with Angelman syndrome (AS), and its detailed characterization and relationship to the genotype (deletion vs nondeletion) is important both for medical practice and for clinical trial design. METHODS AND MATERIALS: We retrospectively analyzed the main clinical features of epilepsy in 265 children with AS who were enrolled in the AS Natural History Study, a multicenter, observational study conducted at six centers in the United States. Participants were prospectively followed up and classified by genotype. RESULTS: Epilepsy was reported in a greater proportion of individuals with a deletion than a nondeletion genotype (171 of 187 [91%] vs. 48 of 78 [61%], P < 0.001). Compared with participants with a nondeletion genotype, those with deletions were younger at the time of the first seizure (age: median [95% confidence interval]: 24 [21-24] months vs. 57 [36-85] months, P < 0.001) and had a higher prevalence of generalized motor seizures. Hospitalization following a seizure was reported in more children with a deletion than a nondeletion genotype (92 of 171 [54%] vs. 17 of 48 [36%], P = 0.04). The overall prevalence of absence seizures was not significantly different between genotype groups. Forty-six percent (102/219) of the individuals reporting epilepsy were diagnosed with AS concurrently or after their first seizure. CONCLUSIONS: Significant differences exist in the clinical expression of epilepsy in AS according to the underlying genotype, with earlier age of onset and more severe epilepsy in individuals with AS due to a chromosome 15 deletion.

Henoch-Schönlein purpura and Crohn's disease in a family.

A 16-year-old female who underwent an appendicectomy had terminal segmental ileitis, and developed Henoch-Schonlein purpura (HSP) a few days later. Her brother had suffered from post-infection HSP, while her mother has suffered from Crohn's disease. Human leukocyte antigen (HLA) typing in the patient disclosed the DRB1*11 allele, which has been reported to be associated with HSP, but the brother proved negative, suggesting that this allele was irrelevant to the HSP pathogenesis. The patient and the other relatives did not disclose HLA DRB1*01, which is the only class II phenotype reported to be associated with both diseases. While this case report lends support to the idea that the earlier observation of concomitant Crohn's disease and HSP in the same patients is no chance association, it suggests that if the two pathological conditions share a common genetic background, this does not seem to be related to class II HLA phenotypes. Other, as yet unknown genes could be involved.

The effects of pregnancy on right ventricular remodeling in women with repaired tetralogy of Fallot.

OBJECTIVES: The aim of this study was to better understand the quantitative volumetric changes associated with pregnancy in women with repaired tetralogy of Fallot (TOF), utilizing sequential cardiovascular magnetic resonance (CMR) imaging. BACKGROUND: An increasing number of women with repaired TOF are reaching childbearing age. Limited echocardiographic studies suggest accelerated remodeling of the right ventricle (RV) in women with repaired TOF after pregnancy. METHODS: Sequential CMRs from a group of women with repaired TOF who completed pregnancy and from a matched comparison group of nulliparous women with repaired TOF were evaluated. The two groups were matched according to baseline QRS duration, RV end-diastolic volume (EDV), age at CMR and time between CMRs. Longitudinal change of CMR parameters was compared between the groups. RESULTS: Thirteen women (mean age 26.6 ± 7.4 years) with repaired TOF who completed pregnancy and 26 nulliparous women with repaired TOF (mean age 22.6 ± 8.0 years) were included in this analysis. The rate of increase of RV EDV in the pregnancy group was higher than the comparison group (4.1 ± 1.1 ml/m(2)/year vs. 1.6 ± 0.6 ml/m(2)/year, p=0.07). RV EF did not change significantly in either group. No definitive interaction between degree of pulmonary regurgitation and increase of RV EDV was identified. CONCLUSIONS: Women with repaired TOF who have completed pregnancy appear to experience an accelerated rate of right ventricular remodeling, defined as an increase in end-diastolic volume; however RV systolic function does not deteriorate. Further investigations with a prospective study design, larger cohorts, and longer follow-up are needed to confirm these initial observations.

Two cases of double-outlet left ventricle detected prenatally.

Double-outlet left ventricle is an exceedingly rare congenital heart defect. Its prenatal detection and precise anatomical definition are challenging for a variety of reasons and have never been previously reported. Here described are 2 cases of prenatally diagnosed double-outlet left ventricle. The technical limitations of prenatal diagnosis and its implications for the surgical management of patients affected by such a rare condition are discussed.