Reproductive choices and intrafamilial communication in neurogenetic diseases with different self-estimated severities.

BACKGROUND: Low uptake of presymptomatic testing and medically assisted reproduction in families impacted by neurogenetic diseases prompted us to investigate how reproductive options are considered and whether there is a relationship with perceived severity of the disease. We hypothesised that self-estimated severity would influence opinion on reproductive options and that prenatal/preimplantation diagnosis would be a motivation to inform relatives about their risk. METHODS: We invited people impacted by neurogenetic diseases to evaluate the severity of their familial disease using analogic visual scales and to answer questionnaires about reproductive choices and intrafamilial communication. We compared answers between diseases and with the perceived severity of each disease. RESULTS: We analysed 562 questionnaires. Participants were impacted by Huntington disease (n=307), spinocerebellar ataxias (n=114), Steinert myotonic dystrophy (n=82) and amyotrophic lateral sclerosis/frontotemporal dementia (n=59). Self-estimated severity differed between pathologies (p<0.0001). Overall, participants considered prenatal diagnosis (78.0±34.4 out of 100) and preimplantation diagnosis (75.2±36.1 out of 100) justified more than termination of pregnancy (68.6±38.5 out of 100). They were less in favour of gamete donation (48.3±39.8 out of 100) or pregnancy abstention (43.3±40.3 out of 100). The greater the perceived severity of the disease, the more reproductive options were considered justified, except for gamete donation. Prenatal/preimplantation diagnosis was a motivation to inform relatives for only 55.3% of participants (p=0.01). CONCLUSION: Self-estimated severity minimally impacts opinions towards reproductive options. Medically assisted reproduction procedures are rarely sought and do not motivate familial communication.

Double chromosomal translocation in an infertile man: one-step FISH meiotic segregation analysis and reproductive prognosis.

BACKGROUND: The prevalence of chromosomal translocations is 1/500 in the general population. While in the vast majority of cases, carriers have a normal phenotype; they can present with difficulty conceiving due to the presence of a proportion of unbalanced gametes as a consequence of abnormal chromosomal segregation during meiosis. Since complex translocations involve three or more chromosomes, meiotic segregation leads to a greater number of possible combinations which effectively complicate both their study and therapeutic care. CASE PRESENTATION: We report on the case of a male carrier of a complex homogeneous double Robertsonian translocation: 44, XY, der(13;14)(q10;q10),der(21;22)(q10;q10). We studied his meiotic segregation by FISH on spermatozoa from the initial sample, as well as following discontinuous gradient centrifugation and after incubation in an hypo-osmotic solution. CONCLUSION: We report a method to study in a simple single-step manner the meiotic segregation of double Robertsonian translocations in spermatozoa. Further, our results suggest that reproductive prognosis of affected individuals may be markedly improved by HOST-based sperm selection (HBSS).

End-of-Life Discussions With Patients and Caregivers Affected By Neurogenetic Diseases.

Background and Objectives: No effective cure is available for neurogenetic diseases such as Huntington disease, spinocerebellar ataxias, and Friedreich ataxia, all of which cause progressive motor, cognitive, and psychiatric symptoms leading, in the long term, to severe communication (among other) impairments. In end-of-life situations, advanced directives (indications formulated by the patient about end-of-life choices) are one decision-making resource for relatives, caregivers, and health care professionals. Given the slowly progressive nature of these diseases, the related disabilities, and their hereditary component, patients, caregivers, and neurologists are often at a loss concerning the right course of action to take. Our study's aim was to explore patients' and caregivers' perceptions, needs, and expectations around anticipated end-of-life discussions and advanced directives. Methods: DIRAGENE is an observational, cross-sectional, mixed-methods study with a patient-centered component and a primary caregiver-centered component. Observations include disease severity, psychosocial, and emotional scales; in-house questionnaires; and semidirected interviews. Results: We included 124 participants, of which 81 were patients and 43 primary caregivers. Only 16% of the participants knew specifically about advanced directives and 7% had written documents vs 30% and 18% in the general French population, respectively, adjusted for age. Qualitative analysis of the interviews with 15 couples showed notable dissimilarities in ideas about advanced directives between patients and caregivers and that the underlying pathology, severity, and inheritability are less relevant factors regarding end-of-life discussions than age, environment, prior experiences with death, and history of family illness. Most patients (95%) and caregivers (98%) found that participating in the study was helpful in bringing awareness to end-of-life issues, wished to prioritize discussing them with loved ones, and requested assistance in managing them throughout the course of the disease. Discussion: Being affected by severe neurogenetic diseases does not seem to prompt individuals to give much thought to end-of-life planning. However, patients and caregivers welcome comprehensive information and expect progressive support from trained health care professionals in having such discussions. Routine integration of these conversations into medical management through a holistic and adapted approach will benefit patients with illnesses with unfavorable long-term prognoses.

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.