Informing about genetic risk in families with Huntington disease: comparison of attitudes across two decades.

The low uptake of presymptomatic testing in Huntington disease prompted us to question family members on how they handle the transmission of information regarding genetic risk. We hypothesised that in 2019, parents would inform their at-risk children about their genetic risk more and at a younger age than in 2000, given the availability of prenatal diagnosis, French legislation changes since 2011, and recent therapeutic advances. We made a questionnaire available about the transmission of genetic information within families with Huntington disease in 2000 and 2019. We obtained 443 questionnaires (295 in 2019 and 148 in 2000). Participants were mainly at-risk for Huntington disease (n = 113), affected (n = 85), and spouses (n = 154). In 2019, participants had a higher mean education level (p < 0.01) and a mean age of 44.1 ± 15.1 years (vs 48.1 ± 11.4 years in 2000, p < 0.01). They had been informed about the risk of being a carrier at around 30 years of age (29.0 ± 14.2 in 2019 vs 32.2 ± 13.8 in 2000, p = 0.09). However, they would inform at an earlier age (≤18 years, 67% vs 59%, p = 0.16). Information on transmission risk had been given primarily by parents (45% vs 30%, p = 0.06). In addition, genetic testing for relatives unaware of their status was recommended more frequently in 2019 (46% vs 32%, p < 0.001). Respondents in 2019 recommended genetic testing more often but overall attitudes towards information and testing have not changed significantly over the 19-year time period since the questionnaire was first delivered even despite recent clinical trials potential disease modifying therapies.

Genetic Testing in Prion Disease: Psychological Consequences of the Decisions to Know or Not to Know.

Purpose: Presymptomatic testing for susceptibility to genetic prion diseases is often delivered in difficult circumstances, as the index case is often dying when a genetic diagnosis is obtained. Since test requests in these diseases are very rare, the factors underlying decisions of relatives to be tested or not and the long-term psychological consequences are not reported. Methods: We contacted subjects who had consulted between 2004 and 2017 because a relative carried a pathological PRNP variant. Standardized psychological scales and semistructured interviews were proposed. Results: We did contact 19 of the 30 subjects who had consulted: 6 of 10 who did not undergo testing, 10 of 12 noncarriers, and 3 of 8 mutation carriers. Anxiety rates were high and similar between noncarriers and untested subjects. Conclusions: Living in a family with inherited prion disease produced psychological burden, regardless of the decision to undergo testing and its results. Decisions in favor of being testing did not allow relief of anxiety about the family disease. The dilemmatic decision not to know remained a burden to be coped with. Genetic counseling procedures should take into account all these situations, even that of noncarriers and that of untested.

Corpus Callosum Abnormalities and Short Femurs in Beckwith-Wiedemann Syndrome: A Report of Two Fetal Cases.

INTRODUCTION: Beckwith-Wiedemann syndrome (BWS) is the most common overgrowth syndrome. Clinical features are highly variable, including occasional posterior fossa malformations but no femoral shortening. CASE REPORT: We report two fetuses with BWS associated with short femurs and corpus callosum hypoplasia. Case 2 was growth restricted. BWS was confirmed by molecular studies showing a loss of methylation at ICR2 at 11p15 chromosomic region in case 1 and a gain of methylation at ICR1 and a loss of methylation at ICR2 locus in case 2. CONCLUSION: Although the phenotype and the genotype of BWS is now well-known, the presence of corpus callosum abnormalities and short femurs expand the phenotypic spectrum of the disorder.