Clinical and behavioral features in carriers of intermediate length alleles of HTT gene. A case series of Mexican population

M.A. Ramírez-García, D.J. Dávila-Ortiz de Montellano, P. Yescas-Gómez, A. Ochoa-Morales, C. Boll, M.E. Alonso-Vilatela (Mexico City, Mexico)

Meeting: 2016 International Congress

Abstract Number: 1149

Keywords: Chorea (also see specific diagnoses, etc): Clinical features, etc): Etiology and Pathogenesis, etc): Genetics, Huntingtons disease

Session Information

Date: Wednesday, June 22, 2016

Session Title: Huntington's disease

Session Time: 12:00pm-1:30pm

Location: Exhibit Hall located in Hall B, Level 2

Objective: To describe clinical manifestations in carriers of intermediate alleles (IAs) of CAG trinucleotides in HTT gene of Mexican population.

Background: Huntington’s disease (HD) is a neurodegenerative disorder characterized by behavioral, motor and cognitive impairments. Is caused by a trinucleotide CAG expansion in exon 1 of the HTT gene at chromosome 4p. The most common CAG size in the general population is 17 repeats, the presence of 40 or more CAG repeats confers the classical Huntington disease phenotype, meanwhile 36 to 39 repeats are considered alleles with reduced penetrance with late onset disease. On the other hand, alleles with 27-35 repeats are known as IAs. Previously, it was believed that IAs do not confer disease, however the description of isolated cases with HD phenotype and more recently the two prospectives studies (PHAROS and COHORT) have associated the presence of IAs with more significant behavioral issues but normal motor and cognition abilities.

Methods: After approval by local ethics committee and informed consent, all those subjects who had been previously evaluated to HD molecular test that were resulted with IAs, were included in a group (cases) and were matched with 2 healthy individuals by age and sex (controls). Each group were applied motor scale from Unified HD Rating Scale (UHDRS) and the instrument Problem Behaviors Assessment for HD (PBA-HD). To evaluate differences in the groups Mann-Whitney U test was performed.

Results: The cases group (5 individuals) showed significant differences in most of the items evaluated by motor scale from UHDRS in comparison with controls (

[table1] Motor assessment in AIs carriers and matched controls.
UHDRS Motor Assessment	Cases Median (minimum and maximum)	Controls Median (minimum and maximum)	p value
Ocular pursuit
Horizontal	1 (0-2)	0	.013*
Vertical	1 (0-2)	0	.075
Saccade initiation
Horizontal	2(1-3)	0	.001*
Vertical	2(1-3)	0	.001*
Saccade velocity
Horizontal	2 (1-3)	0	.001*
Vertical	2 (1-3)	0	.001*
Dysarthria	1 (0-2)	0	.075
Tongue protrusion	0 (0-3)	0	.254
Finger taps
Right	2 (0-3)	0	.013*
Left	2 (0-2)	0	.013*
Pronate/supinate-hands
Right	1 (0-4)	0	.075
Left	1 (0-4)	0	.075
Luria	3 (2-4)	0 (0-1)	.001*
Rigidity – Arms
Right	0	0	.593
Left	0	0	1
Bradykinesia	1 (1-3)	0	.008*
Maximal Dystonia
Trunk	1 (0-3)	0	.075
RUE	1 (0-3)	0	.013*
LUE	1 (0-3)	0	.013*
RLE	1 (0-3)	0	.075
LLE	1 (0-3)	0	.075
Maximal Chorea
Face	2 (0-3)	0	.013*
BOL	2 (1-3)	0	.001*
Trunk	1 (0-3)	0	.075
RUE	2 (1-3)	0	.001*
LUE	2 (1-3)	0	.001*
RLE	1 (0-3)	0	.075
LLE	1 (0-3)	0	.075
Gait	2 (0-3)	0	.075
Tandem walking	2 (1-3)	0	.001*
Retropulsion pull test	1 (0-3)	0	.013*
Diagnosis confidence level	2 (1-3)	0	.001*
Motor examination	45 (19-83)	0.5 (0-3)	.001*

*Statistical significance by Mann–Whitney U test), furthermore, differences in psychiatric behavior were found through PBA-HD instrument (

[table2] Behavioral assessment in AIs carriers and matched controls.
PBS-HD	Cases Median (minimum and maximum)	Controls Median (minimum and maximum)	p value
Poor judgment, self-monitoring
Frecuency	3 (1-5)	1 (1-2)	.028*
Irritability
Frecuency	3 (2-5)	1 (1-2)	.008*
Severity	2 (1-3)	0 (0-2)	.005*
Sleeping or drowsy during day
Frecuency	3 (2-5)	2 (1-3)	.019*
Anxiety
Frecuency	3 (3-5)	2 (1-2)	.001*
Loss of volition
Frecuency	3 (1-5)	1 (1-1)	.013*
Severity	1 (0-3)	0 (0-0)	.013*
Pathological preocupations
Frecuency	4 (1-4)	1 (1-3)	.028*
Depressed mood
Severity	3 (1-5)	1.5 (1-2)	.040*

*Statistical significance by Mann–Whitney U test“), significant data in some of the sections that assess apathy, irritability and depression.

Conclusions: The clinical description of our IAs carriers allows us to partake in the deciphering of a newly discovered field in medicine. This contributes widely to know the potential phenotypic spectrum of HD, allowing early assessment and possible treatment to the manifestations present in these individuals. Our research seeks to describe clinical manifestations in carriers of IA, justified in assuming that such alleles are associated with subtle data or mild cases of HD. We can show that motor impairment is bigger than psychiatric disorders in our sample of Mexican individuals with IA.

To cite this abstract in AMA style:

M.A. Ramírez-García, D.J. Dávila-Ortiz de Montellano, P. Yescas-Gómez, A. Ochoa-Morales, C. Boll, M.E. Alonso-Vilatela. Clinical and behavioral features in carriers of intermediate length alleles of HTT gene. A case series of Mexican population [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/clinical-and-behavioral-features-in-carriers-of-intermediate-length-alleles-of-htt-gene-a-case-series-of-mexican-population/. Accessed May 19, 2025.

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