Huntington Disease-Like 2 (HDL2) is a rare autosomal dominant disorder caused by an abnormal CAG/CTG triplet repeat expansion on chromosome 16q24. The symptoms of progressive decline in motor, cognitive and psychiatric functioning are similar to those of Huntington’s disease (HD). The psychiatric features of the HDL2 have been poorly characterized.
Objective:
To describe the neuropsychiatric features of HDL2 and compare them with those of HD.
Methods:
A blinded cross-sectional design was used to compare the behavioural component of the Unified Huntington’s Disease Rating Scale (UHDRS) in participants with HDL2 (n = 15) and HD (n = 13) with African ancestry.
Results:
HDL2 patients presented with psychiatric symptoms involving mood disturbances and behavioural changes that were not significantly different from those in the HD group. Duration of disease and motor performance correlated (p < 0.001) with the Functional Capacity score and the Independence score of the UHDRS. HD patients reported movement dysfunction as the first symptom more frequently than HDL2 Patients (p < 0.001).
Conclusion:
The psychiatric phenotype of HDL2 is similar to that of HD and linked to motor decline and disease duration. Psychiatric symptoms seem more severe for HDL2 patients in the early stages of the disease.
MargolisRL, HolmesSE. Huntington’s disease-like A clinical, pathological, and molecular comparison to Huntington’s disease. Clin Neurosci Res. 2003;3:187–96.
2.
AndersonDG, Ferreira-CorreiaA, RodriguesFB, AzizA, CarrJ, WildEJ, et al.Comparison of the Huntington’s Disease-like 2 and Huntington’s Disease clinical phenotypes. Mov Disord Clin Pract. 2019;6(4):302–11.
3.
Ferreira-CorreiaA, AndersonDG, CockcroftK, KrauseA. The neuropsychological deficits and dissociations in Huntington Disease-Like A series of case-control studies. Neuropsychologia. 2020;136:107238.
4.
WalkerRH, JankovicJ, O’HearnE, MargolisRL. Phenotypic features of Huntington’s disease-like 2. Mov Disord. 2003;18(12):1527–30.
KrauseA, MitchellC, EssopF, TagerS, TemlettJ, StevaninG, et al.Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype. Am J Med Genet B Neuropsychiatr Genet. 2015;168(7):573–85.
7.
WalkerRH, RasmussenA, RudnickiDD, HolmesSE, AlonsoE, MatsuuraT, et al.Huntington’s disease–like 2 can present as chorea-acanthocytosis. Neurology.. 2003;61(7):1002–4.
FischerCA, LichtEA, MendezMF. The neuropsychiatric manifestations of Huntington’s disease-like 2. J Neuropsychiatry Clin Neurosci. 2012;24(4):489–92.
10.
SchneiderSA, MarshallKE, XiaoJ, LeDouxMS. JPH3 repeat expansions cause a progressive akinetic-rigid syndrome with severe dementia and putaminal rim in a five-generation African-American family. Neurogenetics. 2012;13(2):133–40.
11.
ParadisiI, IkonomuV, AriasS. Huntington disease-like 2 (HDL2) in Venezuela: Frequency and ethnic origin. J Hum Genet. 2013;58(1):3–6.
12.
EppingEA, MillsJA, BeglingerLJ, FiedorowiczJG, CraufurdD, SmithMM, et al.Characterization of depression in prodromal Huntington disease in the neurobiological predictors of HD (PREDICT-HD) study. J Psychiatr Res. 2013;47(10):1423–31.
13.
BurrowsS, LaflammeL. Suicide mortality in South Africa. Soc Psychiatry Psychiatr Epidemiol. 2006;41(2):108–14.
14.
PeltzerK, CherianV, CherianL. Cross-cultural attitudes towards suicide among South African secondary school pupils. East Afr Med J. 2000;77(3):165–7.
15.
CallaghanJ, StopfordC, ArranN, BoisseMF, ColemanA, SantosRD, et al.Reliability and factor structure of the Short Problem Behaviors Assessment for Huntington’s disease (PBA-s) in the TRACK-HD and REGISTRY studies. J Neuropsychiatry Clin Neurosci. 2015;27(1):59–64.
16.
RudnickiDD, PletnikovaO, VonsattelJ-PG, RossC, MargolisRL. A comparison of Huntington disease and Huntington disease-like 2 neuropathology. J Neuropathol Exp Neurol. 2008;67(4):366–74.
17.
AndersonDG, HaagensenM, Ferreira-CorreiaA, PiersonR, CarrJ, KrauseA, et al.Emerging differences between Huntington’s disease-like 2 and Huntington’s disease: A comparison using MRI brain volumetry. Neuroimage Clin. 2019;21:101666.
18.
MargolisRL, O’HearnE, RosenblattA, WillourV, HolmesSE, FranzML, et al.A disorder similar to Huntington’s disease is associated with a novel CAG repeat expansion. Ann Neurol. 2001;50(3):373–80.
19.
WalkerRH, MorgelloS, Davidoff-FeldmanB, MelnickA, WalshMJ, ShashidharanP, et al.Autosomal dominant chorea-acanthocytosis with polyglutamine-containing neuronal inclusions. Neurology. 2002;58(7):1031–7.
20.
StevaninG, FujigasakiH, LebreA-S, CamuzatA, JeannequinC, DodéC, et al.Huntington’s disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes. Brain. 2003;126(7):1599–603.
21.
TeiveH, BeckerN, MunhozR, RaskinS, WerneckL, CazeneuveC, et al. Huntington’s disease-like 2: The first case report in Latin America in a patient without African ethnic origin: 85. Mov Disord. 2007;22.
22.
BardienS, AbrahamsF, SoodyallH, van der MerweL, GreenbergJ, BrinkT,et al.. A South African mixed ancestry family with Huntington disease-like Clinical and genetic features. Mov Disord. 2007;22(14):2083–9.
23.
RodriguesGGR, WalkerRH, BriceA, CazeneuveC, RussaouenO, TeiveHA,et al.. Huntington’s disease-like 2 in Brazil— Report of 4 patients. Mov Disord. 2008;23(15):2244–7.
24.
SantosC, WanderleyH, VedolinL, PenaSD, JardimL, SequeirosJ. Huntington disease-like The first patient with apparent European ancestry. Clin Genet. 2008;73(5):480–5.
25.
CastilhosRM, SouzaAFD, FurtadoGV, GhenoTC, SilvaAL, VargasFR,et al.. Huntington disease and Huntington disease-like in a case series from Brazil. Clin Genet. 2014;86(4):373–7.
26.
MarianiL-L, TessonC, CharlesP, CazeneuveC, HahnV, YoussovK,et al.. Expanding the spectrum of genes involved in Huntington disease using a combined clinical and genetic approach. JAMA Neurol. 2016;73(9):1105–14.
27.
VasconcellosLFR, MacêdoP, FranckJB, TumasV, Marques JúniorW, SpitzM. Huntington’s disease like 2 presenting with isolated Parkinsonism. J Neurol Sci. 2017;373:105–6.
