Unraveling the role of relative telomere length and CAG expansion on initial symptoms of juvenile Huntington disease

Abstract

Background and purpose Juvenile‐onset Huntington disease (JHD) is defined when symptoms initiate before 20 years of age. Mechanisms explaining differences between juvenile and adult onset are not fully understood. Our aim was to analyze the distribution of initial symptoms in a cohort of JHD patients and to explore its relationship with CAG expansion and relative telomere length (RTL). Methods A total of 84 JHD patients and 54 neurologically healthy age and sex matched individuals were recruited. CAG length was measured by southern blot or triplet repeat primed polymerase chain reaction. RTL was measured using the Cawthon method. Results Psychiatric symptoms were most frequent when considering the entire cohort. When divided into onset before or after 10 years, cognitive symptoms were more frequent in the youngest, whilst in the older group psychiatric symptoms prevailed. Motor symptoms were rare in the youngest and epilepsy was observed only in this group as well as a larger CAG expansion. RTL analysis revealed shorter telomeres in JHD patients compared to controls. This difference is not influenced by age, initial symptoms, time of disease or CAG expansion. Conclusions To the best of our knowledge this is the largest cohort of JHD patients reported. Psychiatric manifestations deserve special attention when JHD is suspected and epilepsy is especially important in the youngest patients. Initial symptoms seem to be influenced by CAG expansion and therefore age of onset. RTL is significantly reduced in JHD patients which can influence the characteristic neurodegeneration of JHD and contribute to the clinical discrepancy between adult and juvenile forms of Huntington disease.

Pearls & Oy-sters: Epilepsy Is a Key Feature of Pediatric-Onset Huntington Disease

“…3,4 Epilepsy occurs in approximately half of patients with PoHD and is associated with a longer CAG repeat length and younger age at onset. 6-8 Much of the existing literature on seizure prevalence in PoHD dates to before the availability of genetic testing, and to date, there is no prospective analysis of epilepsy in PoHD.…”