F17 ‘sans Famille’ : Huntington’s Disease Patients with Negative Family History in Enroll-HD Dataset

Huntington’s disease (HD) is a rare autosomal dominant neurodegenerative disorder. The onset is typically adult and the clinical profile includes movement disorders, cognitive deficits and behavioural changes. We examined sociodemographic, genetic and clinical characteristics of patients with negative family history of disease extracted from Enroll-HD PDS4. Out of the 5053 European Caucasian adult patients, 630 (12.50%) shared a missing/unknown inheritance status while 44.30% inherited HD from maternal and 43.20% from paternal side. The age of this group was 61.40±12.00; the sex ratio was exactly 50%. The age of onset was 53.78±11.96 and diagnosis was 4 years postponed (57.59±11.94); mean CAG triplets number in larger allele was 42.48±3.14. In 54.70% of subjects, the onset symptom was purely motor; mixed symptoms in 19.10%. Psychiatric onset was reported in 20.60% of patients while cognitive only in 5.40%. Psychiatric anamnesis included depression (pre-HD onset) in 26% of cases, suicidal ideation/behaviours in 25.40%. Alcohol abuse described in 8%. When sporadic HD cases appear, we can hypothesize parental intermediate allele transmission (tardive HD parent healthy until later age, or misdiagnosed). In a minority, adoption or non-paternity made HD not traceable. Further investigation of sociodemographic and clinical characteristics of this population is interesting as they carried on their own life until diagnosis unaware of HD, protected from a well-recognized major existential burden involving personal genetic risk, caregiving for affected family members, multiple losses. The role of life stressors in modulating aspects of disease is still unclear and may offer perspectives of psychobehavioral intervention.