F15 Clinical profile of small expansion carriers with 36–38 CAG HTT repeats: a multicentric retrospective study. (12th September 2022)

• Record Type: Journal Article
• Authors: Heinzmann, Anna; Sayah, Sabrina; Lejeune, Francois Xavier; Hahn, Valérie; Teichmann, Marc; Monin, Marie Lorraine; Marchionni, Enrica; Gérard, Fleur; Charles, Perrine; Pariente, Jérémie; Durr, Alexandra
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 93(2022)Supplement 1
• Page Start: A41
• Page End: A41
• Publication Date: 2022-09-12
• Subjects: Small expansions -- low penetrance alleles -- cognition -- genetic counseling; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2022-ehdn.106
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Background: HTT alleles with a CAG repeat length of 36-38 are known to be associated with later age of onset and milder disease. Aims: Determine the clinical profile of patients with 36-38 CAG in HTT since existing literature is rare. Methods: We analyzed 35 individuals (17 presymptomatic and 18 symptomatic) carrying 36-38 CAG repeats in HTT. Eleven patients underwent deep cognitive phenotyping, compared to 11 patients with 40-42 CAG repeats. We also analyzed an independent cohort of 36-38 CAG carriers from the ENROLL database and compared them to higher CAG groups. Results: The 36-38 CAG cohort showed no significant difference for age at onset compared to the 40-42 CAG group. Unexpectedly, the clinical profile in the small expansion group was not milder. Global cognitive efficiency and performance in different cognitive subdomains were similar without significant age difference at neuropsychological evaluation. Motor scores at first contact were similar, but chorea as the first presenting symptom was significantly less frequent in the 36-38 CAG group (p=0.0351). This was confirmed in the ENROLL database. Additionally, the clinician was significantly less confident to diagnose motormanifest HD (p=2.407e-08) and diagnosis was significantly later in the 36-38 group (p=2.2e-6) despite same age of estimated symptom onset. Conclusions: We showed that small expansion carriers are as severely affected as patients with common expansions. They present with a non-specific motor profile, which seems to result in less confidence and greater delay to diagnose manifest disease. This should be taken into account for genetic counseling and diagnosis.