The association of CAG repeat length with clinical progression in Huntington disease

Neurology ◽  
2006 ◽  
Vol 66 (7) ◽  
pp. 1016-1020 ◽  
Author(s):  
A. Rosenblatt ◽  
K. -Y. Liang ◽  
H. Zhou ◽  
M. H. Abbott ◽  
L. M. Gourley ◽  
...  
Keyword(s):  
Huntington Disease ◽  
Linear Models ◽  
Motor Impairment ◽  
Repeat Length ◽  
Cag Repeat ◽  
Clinical Progression ◽  
Cag Expansion ◽  
Rate Of Progression ◽  
State Examination

Objective: To determine whether the rate of clinical progression in Huntington disease (HD) is influenced by the size of the CAG expansion.Methods: The dataset consisted of 3,402 examinations of 512 subjects seen through the Baltimore Huntington's Disease Center. Subjects were seen for a mean of 6.64 visits, with mean follow-up of 6.74 years. Subjects were administered the Quantified Neurological Examination, with its subsets the Motor Impairment and Chorea Scores, the Mini-Mental State Examination, and the HD Activities of Daily Living (ADL) Scale.Results: In an analysis based on the Random Effects Model, CAG length was significantly associated with the rate of progression of all measures except chorea and ADL. There was a significant interaction term between CAG length and disease duration for all measures except chorea. Further graphical exploration of the data supported these linear models and suggested that subjects at the low end of the expanded CAG repeat range may experience a more benign late course.Conclusions: CAG repeat length has a small effect on rate of progression that may be clinically important over time. Individuals with the shortest expansions appear to have the best prognosis. These effects of the CAG length may be relevant in the analysis of clinical trials.

scholarly journals Incidence of Huntington disease in a northeastern Spanish region: a 13-year retrospective study at tertiary care centre

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Paula Sienes Bailo ◽  
Raquel Lahoz ◽  
Juan Pelegrín Sánchez Marín ◽  
Silvia Izquierdo Álvarez
Keyword(s):  
Retrospective Study ◽  
Huntington Disease ◽  
Tertiary Care ◽  
Genetic Diagnosis ◽  
Repeat Length ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Incomplete Penetrance ◽  
Predictive Test ◽  
Incident Cases

Abstract Background Despite the progress in the knowledge of Huntington disease (HD) in recent years, the epidemiology continues uncertain, so the study of incidence becomes relevant. This is important since various factors (type of population, diagnostic criteria, disease-modifying factors, etc.) make these data highly variable. Therefore, the genetic diagnosis of these patients is important, since it unequivocally allows the detection of new cases. Methods Descriptive retrospective study with 179 individuals. Incidence of HD was calculated from the ratio of number of symptomatic cases newly diagnosed per 100,000 inhabitants per year during the period 2007–2019 in Aragon (Spain). Results 50 (27.9%) incident cases of HD (CAG repeat length ≥ 36) were identified from a total of 179 persons studied. The remaining 129/179 (72.1%) were HD negative (CAG repeat length < 36). 29 (58.0%) females and 21 (42.0%) males were confirmed as HD cases. The overall incidence was 0.648 per 100,000 patient-years. 11/50 positive HD cases (22.0%) were identified by performing a predictive test, without clinical symptoms. The minimum number of CAG repeats found was 9 and the most common CAG length among HD negative individuals was 16. Conclusions Our incidence lied within the range reported for other Caucasian populations. Implementation of new techniques has allowed to determine the exact number of CAG repeats, which is especially important in patients with triplet expansions in an HD intermediate and/or incomplete penetrance allele, both in diagnostic, predictive and prenatal tests.

Conservative management of ossification of the posterior longitudinal ligament

2011 ◽  
Vol 30 (3) ◽  
pp. E2 ◽  
Author(s):  
Martin H. Pham ◽  
Frank J. Attenello ◽  
Joshua Lucas ◽  
Shuhan He ◽  
Christopher J. Stapleton ◽  
...  
Keyword(s):  
Conservative Management ◽  
Japanese Orthopaedic Association ◽  
Posterior Longitudinal Ligament ◽  
Japanese Orthopaedic Association Score ◽  
Clinical Progression ◽  
Association Score ◽  
Rate Of Progression ◽  
The Mean ◽  
High Chance

Object Ossification of the posterior longitudinal ligament (OPLL) can result in significant myelopathy. Surgical treatment for OPLL has been extensively documented in the literature, but less data exist on conservative management of this condition. Methods The authors conducted a systematic review to identify all reported cases of OPLL that were conservatively managed without surgery. Results The review yielded 11 published studies reporting on a total of 480 patients (range per study 1–359 patients) over a mean follow-up period of 14.6 years (range 0.4–26 years). Of these 480 patients, 348 (72.5%) were without myelopathy on initial presentation, whereas 76 patients (15.8%) had signs of myelopathy; in 56 cases (15.8%), the presence of myelopathy was not specified. The mean aggregate Japanese Orthopaedic Association score on presentation for 111 patients was 15.3. Data available for 330 patients who initially presented without myelopathy showed progression to myelopathy in 55 (16.7%), whereas the other 275 (83.3%) remained progression free. In the 76 patients presenting with myelopathy, 37 (48.7%) showed clinical progression, whereas 39 (51.5%) remained clinically unchanged or improved. Conclusions Patients who present without myelopathy have a high chance of remaining progression free. Those who already have signs of myelopathy at presentation may benefit from surgery due to a higher rate of progression over continued follow-up.

scholarly journals Association between Age and Striatal Volume Stratified by CAG Repeat Length in Prodromal Huntington Disease

PLoS Currents ◽  
2011 ◽  
Author(s):  
Elizabeth Aylward ◽  
James Mills ◽  
Dawei Liu ◽  
Peggy Nopoulos ◽  
Christopher A. Ross ◽  
...  
Keyword(s):  
Huntington Disease ◽  
Repeat Length ◽  
Cag Repeat

scholarly journals Association between Age and Striatal Volume Stratified by CAG Repeat Length in Prodromal Huntington Disease

PLoS Currents ◽  
2011 ◽  
Vol 3 ◽  
pp. RRN1235 ◽  
Author(s):  
Elizabeth Aylward ◽  
James Mills ◽  
Dawei Liu ◽  
Peggy Nopoulos ◽  
Christopher A. Ross ◽  
...  
Keyword(s):  
Huntington Disease ◽  
Repeat Length ◽  
Cag Repeat

scholarly journals Incidence of Huntington disease in a northeastern Spanish region: A 13-year retrospective study at tertiary care centre

2020 ◽  
Author(s):  
Paula Sienes Bailo ◽  
Raquel Lahoz ◽  
Juan Pelegrín Sánchez Marín ◽  
Silvia Izquierdo Álvarez
Keyword(s):  
Retrospective Study ◽  
Huntington Disease ◽  
Tertiary Care ◽  
Genetic Diagnosis ◽  
Repeat Length ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Incomplete Penetrance ◽  
Predictive Test ◽  
Incident Cases

Abstract Background: Despite the progress in the knowledge of Huntington disease (HD) in recent years, the epidemiology continues uncertain, so the study of incidence becomes relevant. This is important since various factors (type of population, diagnostic criteria, disease-modifying factors, etc.) make these data highly variable. Therefore, the genetic diagnosis of these patients is important, since it unequivocally allows the detection of new cases.Methods: Descriptive retrospective study with 179 individuals. Incidence of HD was calculated from the ratio of number of symptomatic cases newly diagnosed per 100 000 inhabitants per year during the period 2007-2019 in Aragon (Spain).Results: 50 (27.9%) incident cases of HD (CAG repeat length ≥36) were identified from a total of 179 persons studied. The remaining 129/179 (73.4%) were HD negative (CAG repeat length <36). 29 (58.0%) females and 21 (42.0%) males were confirmed as HD cases. The overall incidence was 64.8 per 100 000 patient-years. 11/50 positive HD cases (22.0%) were identified by performing a predictive test, without clinical symptoms. The minimum number of CAG repeats found was 10 and the most common CAG length among HD negative individuals was 16.Conclusions: Our incidence lied within the range reported for other Caucasian populations. Implementation of new techniques has allowed to determine the exact number of CAG repeats, which is especially important in patients with triplet expansions in an HD intermediate and/or incomplete penetrance allele, both in diagnostic, predictive and prenatal tests.

The relationship between CAG repeat length and clinical progression in Huntington's disease

2008 ◽  
Vol 23 (9) ◽  
pp. 1223-1227 ◽  
Author(s):  
Bernard Ravina ◽  
Megan Romer ◽  
Radu Constantinescu ◽  
Kevin Biglan ◽  
Alicia Brocht ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Repeat Length ◽  
Cag Repeat ◽  
Clinical Progression ◽  
The Relationship

scholarly journals Incidence of Huntington disease in a northeastern Spanish region: A 13-year retrospective study at tertiary care centre

2020 ◽  
Author(s):  
Paula Sienes Bailo ◽  
Raquel Lahoz ◽  
Juan Pelegrín Sánchez Marín ◽  
Silvia Izquierdo Álvarez
Keyword(s):  
Retrospective Study ◽  
Huntington Disease ◽  
Tertiary Care ◽  
Genetic Diagnosis ◽  
Repeat Length ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Incomplete Penetrance ◽  
Predictive Test ◽  
Incident Cases

Abstract Background: Despite the progress in the knowledge of Huntington disease (HD) in recent years, the epidemiology continues uncertain, so the study of incidence becomes relevant. This is important since various factors (type of population, diagnostic criteria, disease-modifying factors, etc.) make these data highly variable. Therefore, the genetic diagnosis of these patients is important, since it unequivocally allows the detection of new cases.Methods: Descriptive retrospective study with 179 individuals. Incidence of HD was calculated from the ratio of number of symptomatic cases newly diagnosed per 100 000 inhabitants per year during the period 2007-2019 in Aragon (Spain). Results: 50 (27.9%) incident cases of HD (CAG repeat length ≥36) were identified from a total of 179 persons studied. The remaining 129/179 (73.4%) were HD negative (CAG repeat length <36). 29 (58.0%) females and 21 (42.0%) males were confirmed as HD cases. The overall incidence was 64.8 per 100 000 patient-years. 11/50 positive HD cases (22.0%) were identified by performing a predictive test, without clinical symptoms. The minimum number of CAG repeats found was 10 and the most common CAG length among HD negative individuals was 16.Conclusions: Our incidence lied within the range reported for other Caucasian populations. Implementation of new techniques has allowed to determine the exact number of CAG repeats, which is especially important in patients with triplet expansions in an HD intermediate and/or incomplete penetrance allele, both in diagnostic, predictive and prenatal tests.

scholarly journals Endophenotypical drift in Huntington’s disease: a 5-year follow-up study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Marie N. N. Hellem ◽  
Rebecca K. Hendel ◽  
Tua Vinther-Jensen ◽  
Ida U. Larsen ◽  
Troels T. Nielsen ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Disease Burden ◽  
Psychiatric Symptoms ◽  
Cag Repeat ◽  
Symptom Trajectories ◽  
Younger Age ◽  
Cardinal Symptoms ◽  
State Examination

Abstract Background Huntington’s disease (HD) is clinically characterized by progressing motor, cognitive and psychiatric symptoms presenting as varying phenotypes within these three major symptom domains. The disease is caused by an expanded CAG repeat tract in the huntingtin gene and the pathomechanism leading to these endophenotypes is assumed to be neurodegenerative. In 2012/2013 we recruited 107 HD gene expansion carriers (HDGECs) and examined the frequency of the three cardinal symptoms and in 2017/2018 we followed up 74 HDGECs from the same cohort to describe the symptom trajectories and individual drift between the endophenotypes as well as potential predictors of progression and remission. Results We found higher age to reduce the probability of improving on psychiatric symptoms; increasing disease burden score ((CAG-35.5) * age) to increase the risk of developing cognitive impairment; increasing disease burden score and shorter education to increase the risk of motor onset while lower disease burden score and higher Mini Mental State Examination increased the probability of remaining asymptomatic. We found 23.5% (N = 8) to improve from their psychiatric symptoms. Conclusions There is no clear pattern in the development of or drift between endophenotypes. In contrast to motor and cognitive symptoms we find that psychiatric symptoms may resolve and thereby not entirely be caused by neurodegeneration. The probability of improving from psychiatric symptoms is higher in younger age and advocates for a potential importance of early treatment.

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