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ObjectiveWe aimed to describe the population of subjects seeking presymptomatic counseling for amyotrophic lateral sclerosis and/or frontotemporal dementia (ALS/FTD) and compared them with those demanding the well-established presymptomatic test for Huntington disease (HD).MethodsWe retrospectively examined the requests of a cohort of individuals at risk of familial ALS/FTD and 1 at risk of HD over the same time frame of 11 years. The individuals were seen in the referral center of our neurogenetics unit.ResultsOf the 106 presymptomatic testing (PT) requests from subjects at risk of ALS/FTD, 65% were seen in the last 3 years. Over two-thirds of the subjects were at risk of carrying mutations responsible for ALS, FTD, or both. Sixty-two percent of the subjects came from families with a known hexanucleotide repeat expansion in C9ORF72. During the same period, we counseled 840 subjects at risk of HD. Subjects at risk of ALS/FTD had the presymptomatic test significantly sooner after being aware of their risk, but were older than those at risk of HD. The youngest subjects requesting the test had the highest disease load in the family (p < 0.05).ConclusionsDemands for PT for ALS/FTD have been increasingly growing, particularly since the discovery of the C9ORF72 gene. The major specificity of the genetic counseling for these diseases is the unpredictability of the clinical phenotype for most of the genes involved. Awareness of this added uncertainty does not prevent individuals from taking the test, as the dropout rate is not higher than that for HD.

Predictive genetic testing (PGT) is offered to asymptomatic relatives at risk of hereditary heart disease, but the impact of result disclosure has been little studied. We evaluated the psychosocial impacts of PGT in hereditary heart disease, using self-report questionnaires (including the State-Trait Anxiety Inventory) in 517 adults, administered three times to the prospective cohort (PCo: n = 264) and once to the retrospective cohort (RCo: n = 253). The main motivations for undergoing PGT were &ldquo, to remove doubt&rdquo, and &ldquo, for their children&rdquo, The level of anxiety increased between pre-test and result appointments (p &lt, 0.0001), returned to baseline after the result (PCo), and was moderately elevated at 4.4 years (RCo). Subjects with a history of depression or with high baseline anxiety were more likely to develop anxiety after PGT result (p = 0.004 and p &lt, 0.0001, respectively), whatever it was. Unfavourable changes in professional and/or family life were observed in 12.4% (PCo) and 18.7% (RCo) of subjects. Few regrets about PGT were expressed (0.8% RCo, 2.3% PCo). Medical benefit was not the main motivation, which emphasises the role of pre/post-test counselling. When PGT was performed by expert teams, the negative impact was modest, but careful management is required in specific categories of subjects, whatever the genetic test result.

Background Hypertrophic cardiomyopathy (HCM) is a genetic disease with delayed cardiac expression. Family screening strategy includes cardiac screening that may be guided by predictive genetic testing (PGT). However, little is known about the impact of PGT and the risk factors present at the very early stage of the disease. Purpose Our study aims to evaluate the impact of predictive genetic testing on the rate of initiation of cardiac screening, to estimate the penetrance of HCM and to determine the frequency of risk factors (RF) for sudden cardiac death in individuals at preclinical stage without HCM. Results We studied 60 consecutive relatives in a single center (31 women and 29 men, mean age: 34 ± 16.3 years) without history of HCM before genetic testing and who were mutation carriers after PGT. Cardiac screening was initiated before PGT in only 37%, and was started after PGT in 63%. Echocardiographic criteria for HCM were observed in 17% (28% of men but 6% of women, 17% of MYH7 mutation carriers but 0% in MYBPC3 carriers). Among mutation carriers without hypertrophy (n = 50), 1 had non-sustained ventricular tachycardia, 2 had non-explained syncope and 5 presented with family history of sudden death. In addition, 14% had dilated left atrium, 2% a high risk mutation and 8% practiced intense physical activity. Moreover, 10% (2/21) of carriers who performed MRI had cardiac fibrosis and 3% (1/32) of carriers who performed Holter monitoring had significant premature ventricular beat (PVB > 240/day). Conclusion The assessment of HCM causal mutations in relatives seems to be an important step to initiate cardiac screening. The penetrance of HCM seems to be higher in the male population and in MYH7 rather than in other genes mutation carriers. Mutations carriers at a preclinical stage without hypertrophy may have individual risk factors of sudden cardiac death. Further study of a larger population may be useful to confirm these results.

Introduction Hereditary heart diseases are most often characterized by autosomal dominant inheritance and delayed cardiac expression. Predictive genetic testing is offered to asymptomatic relatives to allow targeted medical care with early therapeutics in order to reduce the risk of complications. Psychological issues and socio-professional impact of predictive testing are complex and have been poorly studied. The aim of this study was to evaluate the psychological and socio-professional impact of predictive genetic testing in hereditary heart diseases through a prospective and retrospective study. Patients and methods This multicentric French study involved 20 expert centers in hereditary heart diseases. We included 517 adult relatives (42.3±16.7 years, 60.6% females) who performed predictive genetic testing (prospective study: N=264, retrospective study: N=253). The opinion and experience were collected via auto-questionnaires, at various moments in the prospective study, with different items and validated scales (STAI: score for anxiety and IES: impact of event). Results In the prospective study, family history was characterized by cardiomyopathy (88.4%) and channelopathies (11.6%). The main motivations for performing the test were: “to remove doubt” (65.3%), “for children” (64.0%), “to benefit from medical supervision” (34.9%). A mutation was present in 39.4% of relatives. No regret was expressed after testing (only 2.3% regrets). The result did not lead to a socio-professional change or family relationship change in 60.7%. Among those who had a change, it was perceived as unfavorable for only 3%. A change in socio-professional status and/or family relationship was mainly related to the result of genetic testing (p Conclusions Our results show that contrary to a widespread opinion, the medical benefit was not the main motivation for predictive genetic testing. In most cases, no or marginal adverse psychological and socio-professional impact of genetic testing was observed when performed by a team expert in predictive testing. However careful management is required to identify and manage subjects at risk for increased anxiety or socio-professional change.

RASA1-related disease is a rare autosomal dominant disease characterized by capillary malformations, arteriovenous malformations (AVMs), and/or arteriovenous fistulas (AFVs). Penetrance is nearly complete and vascular malformations may cause serious complications such as organ injury due to oxygenation disorder, brain abscess, hemorrhage, and stroke. Early diagnosis is useful in order to discuss optimal management, including AVMs/AVFs embolization or surgical procedures, and try to prevent some of the complications. In this context, molecular testing of RASA1 gene mutation in relatives may help to better manage the family. All arteriovenous malformations are however not accessible to such procedures. In addition, these therapeutic procedures may result in potential side effects and complications. A couple was referred to our genetics unit and asked us for prenatal genetic testing about a RASA1 mutation. Here, we discuss about arguments that led our team to accept prenatal testing. To the best of our knowledge, no molecular prenatal diagnosis was reported until now in RASA1-related diseases. This first report of prenatal diagnosis in RASA1-related diseases may also offer perspectives for a more general discussion in the field of inherited arteriovenous malformations.

Adnexal torsion (AT) is difficult to diagnose and requires immediate surgery. The aim of this study was to develop a simple score for assisting in the pre-operative diagnosis of AT in women with acute pelvic pain.Using data from a retrospective cohort of 142 patients with acute pelvic pain, we developed a score based on multiple logistic regression after a jackknife procedure. We validated the score in a prospective cohort of 35 women with acute pelvic pain.Five criteria were independently associated with AT confirmed by surgery: unilateral lumbar or abdominal pain [adjusted odds ratio (aOR), 4.1; 95% confidence interval (95% CI), 1.2-14.0]; pain duration8 h at first presentation (aOR, 8.0; 95% CI, 1.7-37.5), vomiting (aOR, 7.9; 95% CI, 2.3-27.0), absence of leucorrhoea and metrorrhagia (aOR, 12.6; 95% CI, 2.3-67.6) and ovarian cyst larger than 5 cm by ultrasonography (aOR, 10.6; 95% CI, 2.9-38.8). The torsion score was based on these five criteria. Low-risk and high-risk groups were derived from values of the score [probability of AT, 3.7% (95% CI, 0-7.8) and 69% (95% CI, 53-84), respectively]. Application of these criteria to the prospective cohort confirmed the diagnostic accuracy of the score [probability of AT, 0% (95% CI, 0-16) and 75% (95% CI, 26-100) in the low-risk and high-risk groups, respectively].This easy-to-calculate score may prove useful for diagnosing AT in patients with acute pelvic pain seen at general or gynaecology emergency departments.

Study question How do fully-comprehensive patient-centred descriptions of the symptoms of endometriosis compare with the physicians' description of the symptoms? Summary answer The description of the painful symptoms due to endometriosis is based on numerous distinct parameters. The way these are used to describe symptoms and the way they are interpreted varies significantly between patients and clinicians. The descriptions of severe pelvic pain and dysmenorrhoea and dyspareunia by the clinicians were incomplete compared with those of the patients. What is known already Painful symptoms due to endometriosis were found to be of little use to predict the location and severity of the disease. Currently there are few data on the patients' description of symptoms and no questionnaire is available to derive data from patients. Study design, size, duration Descriptions of painful symptoms by patients and by physicians were obtained by qualitative, interview-based study and analysed using Colaizzi's method. The patients planned to be operated on for painful endometriosis were volunteers for preoperative interview. They were recruited by purposeful sampling to represent different types of endometriosis [i.e. superficial endometriosis, ovarian endometriosis or deeply infiltrating endometriosis (DIE)], the women were selected so that at least five sites of endometriosis were included in the study. The clinicians were experts in endometriosis management. Participants/materials, setting, methods Forty-one patients were recruited, in four reference centres. Among them, 33 had DIE in various locations, including intestinal endometriosis (n = 12) or bladder endometriosis (n = 5), 14 had ovarian endometriosis (including three without associated DIE) and 5 had only superficial endometriosis. The nine experts were French-speaking gynaecological surgeons practicing in university teaching hospitals (seven), a general hospital (one) or a private centre (one). Main results and the role of chance In total, 47 themes were identified of which 30 were perceived by both patients and clinicians, 12 by patients only and 5 by clinicians only. Themes fall into five general categories: (i) severe pelvic pain and dysmenorrhoea, (ii) dyspareunia, (iii) gastro-intestinal symptoms, (iv) bladder symptoms, (v) other symptoms. Patients' and clinicians' descriptions of symptoms were in agreement for general categories, but the clinicians' comprehensive description was incomplete, in particular concerning the severe pelvic pain and dysmenorrhoea's themes and the dyspareunia theme. Patients did not report any clear-cut distinction between pelvic pain and dysmenorrhoea and expressed a dimension of suffering and impaired quality of life inherent to painful symptoms. Limitations, reasons for caution Most of the patients in the study had already had treatment for endometriosis, including ongoing hormonal treatment. Furthermore, all but a few patients had documented endometriotic lesions and no specific investigations to eliminate additional causes of functional pelvic pain were done. Finally due to the qualitative design of the study the result must be regarded as inferences. Wider implications of the findings The present study provides a first person viewpoint of the painful experience of endometriosis by the patients in a subjective, phenomenological perspective, and points out the differences of perceptions between the physicians and the patients. The considerable variability in patients' descriptions suggests several distinct mechanisms are involved in explaining the pain related to endometriosis. The discordance between clinicians and patients might also reflect this kind of problem with the wording of the items. In future, if the goal is to properly understand the pain experienced by women with endometriosis, assessment tools using the words and phrases used in narratives of pain would potentially be very useful. Study funding/competing interest(s) Funded by IPSEN, Boulogne-Billancourt, France. None of the authors has any conflict of interest to declare. Trial registration number Not applicable.

Background Testing for Huntington’s disease (HD) is usually restricted to individuals at 50% risk in whom the parent is diagnosed with HD. An individual at 25% risk requests testing with full knowledge that the transmiting parent does not want to know. International recommendations states that extreme care should be exercised when PT would provide information about another person who has not requested it. Aims Since 1992, PT is offered in the Salpetriere University Hospital in Paris. To i) compare outcome of 25% at risk individuals to those of 50%; ii) assess how test information was disclosed in the family and to the parent. Methods We assessed information about pretest and post-test information including age, gender, parent status, motivation for testing, result of the PT and contacted 25% at risk individuals by phone and invited them for a semi-structured interview. Results There were 1488 individuals at 50% risk and 159 at 25% who took the test between 1992 and 2016. Sixteen interviews in carriers and non carriers of the mutations were conducted, 5 lost to follow up. The mean time since testing request was similar in both groups [10.9 years ± 6.4 vs 11.4 years ± 6.5 p = 0.416]. 25% at risk were younger at first contact [30.7 ± 9.7 years (13–78) vs 35.1 ± 12.1 years (11–90), p Conclusions Our results showed significant differences between the 25% and 50% at risk groups. In case of an unfavourable result, “double knowledge” had major implications for future relations between child and parent. Psychological issues, particularly the impact to become a “messenger of bad news” for parents and siblings were amplified in that case.