Introduction: Huntington’s disease (HD) is a neurodegenerative, autosomal dominant disabling condition due to an expansion of the CAG trinucleotide in the HTT gene. Motor, psychiatric, and cognitive disorders characterize it. Chilean reports on HD in the era of molecular diagnosis were wanted. Methods: This is a retrospective analysis of a prospective cohort of patients with HD seen at the Center for Movement Disorders (CETRAM) in Chile between 2013 and 2019. Sociodemographic, genotype, and neuropsychiatric features were investigated. Results: One hundred three probands with HD were identified. The majority (63.1%) were born in the metropolitan region, followed by the VIII and V regions with 8.73% and 7.76%, respectively. When pedigrees were analyzed, ninety unrelated families encompassing 1,007 individuals were identified; among relatives, other 35 manifested HD, and 106 died of HD. Besides, five hundred seventy-nine individuals were at genetic risk. The minimum estimated prevalence of HD in Chile in 2019 was 0.72 × 100,000 inhabitants. The mean CAG repeats (CAGR) of 47.2 ± 10.74 for the expanded allele and 17.93 ± 2.05 for the normal allele. The mean age of onset was 41.39 ± 13.47 years. Juvenile cases represented 7.8% of this cohort, and 4.9% had a late onset. There was a negative correlation between the age of onset and the CAGR of the expanded allele (r =−0.84 p < 0.0001). Besides, 79.6% had a family history of HD. Conclusions: This is the first report characterizing genetics, motor, and neuropsychiatric features in patients with HD in Chile. The mean length of CAGR expansion of the abnormal allele was similar to previous reports in North America (i.e., Mexico and Canada) and higher than that reported in the neighboring country of Argentina. According to previous estimations, the minimal prevalence of HD in Chile may be lower than expected.

1.
Bates
GP
,
Dorsey
R
,
Gusella
JF
,
Hayden
MR
,
Kay
C
,
Leavitt
BR
.
Huntington disease
.
Nat Rev Dis Primers
.
2015
;
1
:
15005
.
2.
MacDonald
ME
,
Ambrose
CM
,
Duyao
MP
,
Myers
RH
,
Lin
C
,
Srinidhi
L
.
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes
.
Cell
.
1993
;
72
(
6
):
971
83
.
3.
Zuccato
C
,
Valenza
M
,
Cattaneo
E
.
Molecular mechanisms and potential therapeutical targets in huntington’s disease
.
Physiol Rev
.
2010
;
90
(
3
):
905
81
.
4.
Losekoot
M
,
Van Belzen
MJ
,
Seneca
S
,
Bauer
P
,
Stenhouse
SAR
,
Barton
DE
.
EMQN/CMGS best practice guidelines for the molecular genetic testing of huntington disease
.
Eur J Hum Genet
.
2013
;
21
(
5
):
480
6
.
5.
Squitieri
F
,
Jankovic
J
.
Huntington’s disease: how intermediate are intermediate repeat lengths
.
Mov Disord
.
2012
;
27
(
14
):
1714
7
.
6.
Tabrizi
SJ
,
Leavitt
BR
,
Landwehrmeyer
GB
,
Wild
EJ
,
Saft
C
,
Barker
RA
.
Targeting Huntingtin expression in patients with huntington’s disease
.
N Engl J Med
.
2019
;
380
(
24
):
2307
16
.
7.
Kay
C
,
Hayden
MR
,
Leavitt
BR
.
Epidemiology of huntington disease
.
Handb Clin Neurol
.
2017
;
144
:
31
46
.
8.
Warby
SC
,
Visscher
H
,
Collins
JA
,
Doty
CN
,
Carter
C
,
Butland
SL
.
HTT haplotypes contribute to differences in Huntington disease prevalence between Europe and East Asia
.
Eur J Hum Genet
.
2011
;
19
(
5
):
561
6
.
9.
Avila-Girón
R
.
U Medical and social aspects of Huntington’s chorea in the state of Zulia, Venezuela
. In:
Barbeau
A
,
Chase
TN
,
Paulson
GW
, editors.
Advances in neurology
New York
Raven-Press
1973
.
10.
Wexler
NS
,
Lorimer
J
,
Porter
J
,
Gomez
F
,
Moskowitz
C
,
Shackell
E
.
Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington’s disease age of onset
.
Proc Natl Acad Sci U S A
.
2004
;
101
(
10
):
3498
503
.
11.
Torres-Ramirez
L
,
Consentino
C
,
Mori
N
.
Actualización sobre la enfermedad de Huntington y repercusión de 30 años en el Instituto Nacional de Ciencias Neurológicas
.
Diagnóstico
.
2008
;
47
:
65
9
.
12.
Castilhos
RM
,
Augustin
MC
,
Santos
JA
,
Perandones
C
,
Saraiva-Pereira
ML
,
Jardim
LB
.
Genetic aspects of Huntington’s disease in Latin America. A systematic review
.
Clin Genet
.
2016
;
89
(
3
):
295
303
.
13.
Cruz-Coke
R
.
Genetic epidemiology of Huntington chorea in Chile
.
Rev Med Chil
.
1987
;
115
:
483
5
.
14.
Cruz-Coke
R
,
Moreno
RS
.
Genetic epidemiology of single gene defects in Chile
.
J Med Genet
.
1994
;
31
(
9
):
702
6
.
15.
HSG
.
Unified huntington’s disease rating scale: reliability and consistency
.
Mov Disord
.
1996
;
11
:
136
42
.
16.
Reilmann
R
,
Leavitt
BR
,
Ross
CA
.
Diagnostic criteria for Huntington’s disease based on natural history
.
Mov Disord
.
2014
;
29
(
11
):
1335
41
.
17.
Jama
M
,
Millson
A
,
Miller
CE
,
Lyon
E
.
Triplet repeat primed PCR simplifies testing for Huntington disease
.
J Mol Diagn
.
2013
;
15
(
2
):
255
62
.
18.
Ruiz-Idiago
JM
,
Floriach
M
,
Mareca
C
,
Salvador
R
,
López-Sendón
JL
,
Mañanés
V
.
Spanish validation of the Problem behaviors assessment: short (PBA-s) for huntington’s disease
.
J Neuropsychiatry Clin Neurosci
.
2017
;
29
(
1
):
31
8
.
19.
Instituto nacional de estadísticas de Chile (INE)
Anuario de estadísticas vitales, 2019. Período de información: 2019
.
2021
.
20.
Fontecilla
O
.
Corea de Huntington
.
Rev Med Chil
.
1914
;
41
:
11
.
21.
Vidal
M
,
Rojas
M
,
Geuloff
RM
.
Corea de Huntington
.
Revisat Chile neuropsiq
.
1970
;
9
:
7
14
.
22.
Montejo
M
.
Enfermedades hereditarias dominantes en un Hospital
.
Rev Med Chil
.
1974
;
102
(
6
):
433
7
.
23.
Couyoumdjian
J
.
El alto comercio de Valparaiso y las grandes casas extranjeras 1880–1930. Una aproximación
.
Historia
.
2000
;
33
:
63
99
.
24.
Fuentes
M
,
Pulgar
I
,
Gallo
C
,
Bortolini
MC
,
Canizales-Quinteros
S
,
Bedoya
G
.
Geografía génica de Chile. Distribución regional de los aportes genéticos Americanos, Europeos y Africanos
.
Rev Med Chil
.
2014
;
142
(
3
):
281
9
.
25.
Cuba
JM
,
Castro
C
,
Benzaquen
M
.
Sobre la Epidemiología de la Corea de Huntington en el Perú
.
Revista neuropsiquiatría
.
1983
;
46
:
114
20
.
26.
Alencar
MA
.
Currently prevalence of huntington’s disease in Feira Grande: Alagoas/Northeastern Brazil
.
J Huntington Disor
.
2013
;
2
:
352
.
27.
Walker
RH
,
Gatto
EM
,
Bustamante
ML
,
Bernal-Pacheco
O
,
Cardoso
F
,
Castilhos
RM
.
Huntington’s disease-like disorders in Latin America and the Caribbean
.
Parkinsonism Relat Disord
.
2018
;
53
:
10
20
.
28.
Pringsheim
T
,
Wiltshire
K
,
Day
L
,
Dykeman
J
,
Steeves
T
,
Jette
N
.
The incidence and prevalence of Huntington’s disease: a systematic review and meta-analysis
.
Mov Disord
.
2012
;
27
(
9
):
1083
91
.
29.
Paradisi
I
,
Hernández
A
,
Arias
S
.
Huntington disease mutation in Venezuela: age of onset, haplotype analyses and geographic aggregation
.
J Hum Genet
.
2008
;
53
(
2
):
127
35
.
30.
Kim
HS
,
Lyoo
CH
,
Lee
PH
,
Kim
SJ
,
Park
MY
,
Ma
H-I
.
Current status of Huntington’s disease in Korea: a nationwide survey and national registry analysis
.
J Mov Disord
.
2015
;
8
(
1
):
14
20
.
31.
Alonso
ME
,
Ochoa
A
,
Boll
MC
,
Sosa
AL
,
Yescas
PLM
,
López
M
.
Clinical and genetic characteristics of Mexican Huntington’s disease patients
.
Mov Disord
.
2009
;
24
(
13
):
2012
5
.
32.
Creighton
S
,
Almqvist
EW
,
MacGregor
D
,
Fernandez
B
,
Hogg
H
,
Beis
J
.
Predictive, pre-natal and diagnostic genetic testing for Huntington’s disease: the experience in Canada from 1987 to 2000
.
Clin Genet
.
2003
;
63
(
6
):
462
75
.
33.
Capiluppi
E
,
Romano
L
,
Rebora
P
,
Nanetti
L
,
Castaldo
A
,
Gellera
C
.
Late-onset Huntington’s disease with 40–42 CAG expansion
.
Neurol Sci
.
2020
;
41
(
4
):
869
76
.
34.
Gatto
E
,
Parisi
V
,
Persi
G
,
Converso
DP
,
Etcheverry
JL
,
Varela
V
.
Clinical and genetic characteristics in patients with Huntington’s Disease from Argentina
.
Parkinsonism Relat Disord
.
2012
;
18
(
2
):
166
9
.
35.
Li
HL
,
Li
XY
,
Dong
Y
,
Zhang
YB
,
Cheng
HR
,
Gan
SR
.
Clinical and genetic profiles in Chinese patients with huntington’s disease: a ten-year multicenter study in China
.
Aging Dis
.
2019
;
10
(
5
):
1003
11
.
36.
Semaka
A
,
Kay
C
,
Doty
CN
,
Collins
JA
,
Tam
N
,
Hayden
MR
.
High frequency of intermediate alleles on Huntington disease-associated haplotypes in British Columbia’s general population
.
Am J Med Genet B Neuropsychiatr Genet
.
2013
162B
8
864
71
.
37.
Falush
D
.
Haplotype background, repeat length evolution, and huntington’s disease
.
Am J Hum Genet
.
2009
;
85
(
6
):
939
42
.
38.
Bates
G
,
Tabrizi
S
,
Jones
L
, editors.
Huntingtons disease
Oxford University Press
2014
.
39.
Victor
R
,
Bidegain
E
,
Vita
M
,
Buzó
R
,
Lescano
A
,
Medina
O
.
Analisis molecular de familias uruguayas con enfermedad de Huntington
.
Archivos de Medicina Interna
.
2014
;
36
:
127
31
.
40.
Bean
L
,
Bayrak-Toydemir
P
.
American College of medical genetics and Genomics standards and guidelines for clinical genetics laboratories, 2014 edition: technical standards and guidelines for huntington disease
.
Genet Med
.
2014
;
16
(
12
):
e2
7
.
41.
Vázquez-Mojena
Y
,
Laguna-Salvia
L
,
Laffita-Mesa
JM
,
González-Zaldívar
Y
,
Almaguer-Mederos
LE
,
Rodríguez-Labrada
R
.
Genetic features of Huntington disease in Cuban population: implications for phenotype, epidemiology and predictive testing
.
J Neurol Sci
.
2013
335
1–2
101
4
.
42.
Agostinho
LDA
,
Rocha
CF
,
Medina-Acosta
E
,
Barboza
HN
,
Da Silva
AFA
,
Pereira
SPF
.
Haplotype analysis of the CAG and CCG repeats in 21 Brazilian families with Huntington’s disease
.
J Hum Genet
.
2012
;
57
(
12
):
796
803
.
43.
Cornejo-Olivas
MR
,
Inca-Martinez
MA
,
Espinoza-Huertas
K
,
Veliz-Otani
D
,
Velit-Salazar
MR
,
Marca
V
.
Clinical and molecular features of late onset huntington disease in a Peruvian cohort
.
J Huntingtons Dis
.
2015
;
4
(
1
):
99
105
.
44.
Van Duijn
E
,
Craufurd
D
,
Hubers
AAM
,
Giltay
EJ
,
Bonelli
R
,
Rickards
H
.
Neuropsychiatric symptoms in a European Huntington’s disease cohort (REGISTRY)
.
J Neurol Neurosurg Psychiatry
.
2014
;
85
(
12
):
1411
8
.
45.
Paulsen
JS
,
Ready
RE
,
Hamilton
JM
,
Mega
MS
,
Cummings
JL
.
Neuropsychiatric aspects of Huntington’s disease
.
J Neurol Neurosurg Psychiatry
.
2001
;
71
(
3
):
310
4
.
46.
Andrew
SE
,
Goldberg
YP
,
Kremer
B
,
Squitieri
F
,
Theilmann
J
,
Zeisler
J
.
Huntington disease without CAG expansion: phenocopies or errors in assignment
.
Am J Hum Genet
.
1994
;
54
(
5
):
852
63
.
You do not currently have access to this content.