Diagnosis of Huntington Disease

Abstract Background: Huntington disease (HD) is a rare, progressive, and fatal autosomal dominant neurodegenerative disorder, typically of adult onset. Methods: We reviewed the literature concerning the molecular diagnosis of HD. Results: The discovery of the genetic etiology of HD, a trinucleotide expansion mutation on chromosome 4p, has led to the development of increasingly reliable and valid diagnostic tests that can be applied to symptomatic patients, individuals at risk for HD but currently asymptomatic, fetuses, and embryos. However, the unstable nature of the HD mutation, the lack of effective treatments for HD, the mid-adulthood age of disease onset, and the existence of disorders with the same clinical presentation but different etiology all complicates diagnostic testing. Conclusion: Conscientious laboratory work, knowledgeable interpretation of genetic test results, and the availability of pre- and posttest counseling are essential components of HD diagnosis.

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Low Psychosine in Krabbe Disease with Onset in Late Infancy: A Case Report

International Journal of Neonatal Screening ◽

10.3390/ijns7020028 ◽

2021 ◽

Vol 7 (2) ◽

pp. 28

Author(s):

Camille S. Corre ◽

Dietrich Matern ◽

Joan E. Pellegrino ◽

Carlos A. Saavedra-Matiz ◽

Joseph J. Orsini ◽

...

Keyword(s):

New York ◽

Enzyme Activity ◽

Clinical Presentation ◽

Neurodegenerative Disorder ◽

New York State ◽

Disease Onset ◽

Early Infancy ◽

Krabbe Disease ◽

Activity Levels ◽

Hematopoietic Stem

Krabbe disease (KD) is a rare inherited neurodegenerative disorder caused by a deficiency in galactocerebrosidase enzyme activity, which can present in early infancy, requiring an urgent referral for hematopoietic stem cell transplantation, or later in life. Newborn screening (NBS) for KD requires identification and risk-stratification of patients based on laboratory values to predict disease onset in early infancy or later in life. The biomarker psychosine plays a key role in NBS algorithms to ascertain probability of early-onset disease. This report describes a patient who was screened positive for KD in New York State, had a likely pathogenic genotype, and showed markedly reduced enzyme activity but surprisingly low psychosine levels. The patient ultimately developed KD in late infancy, an outcome not clearly predicted by existing NBS algorithms. It remains critical that psychosine levels be evaluated alongside genotype, enzyme activity levels, and the patient’s evolving clinical presentation, ideally in consultation with experts in KD, in order to guide diagnosis and plans for monitoring.

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Molecular diagnosis of Huntington disease in Brazilian patients

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2000000100002 ◽

2000 ◽

Vol 58 (1) ◽

pp. 11-17 ◽

Cited By ~ 12

Author(s):

TEREZA C. LIMA E SILVA ◽

HELIANE GUERRA SERRA ◽

CARMEN S. BERTUZZO ◽

ISCIA LOPES-CENDES

Keyword(s):

Molecular Diagnosis ◽

Huntington Disease ◽

Neurodegenerative Disorder ◽

Age At Onset ◽

Disease Onset ◽

Significant Negative Correlation ◽

Cag Repeat ◽

Cag Repeats ◽

Unrelated Control ◽

Intermediate Size

Huntington disease (HD) is a progressive neurodegenerative disorder with autosomal dominant inheritance, characterized by choreiform movements and cognitive impairment. Onset of symptoms is around 40 years of age and progression to death occurs in approximately 10 to 15 years from the time of disease onset. HD is associated with an unstable CAG repeat expansion at the 5' and of the IT15 gene. We have genotyped the CAG repeat in the IT15 gene in 44 Brazilian individuals (42 patients and 2 unaffected family members) belonging to 34 unrelated families thought to segregate HD. We found one expanded CAG allele in 32 individuals (76%) belonging to 25 unrelated families. In these HD patients, expanded alleles varied from 43 to 73 CAG units and normal alleles varied from 18 to 26 CAGs. A significant negative correlation between age at onset of symptoms and size of the expanded CAG allele was found (r=0.6; p=0.0001); however, the size of the expanded CAG repeat could explain only about 40% of the variability in age at onset (r2=0.4). In addition, we genotyped 25 unrelated control individuals (total of 50 alleles) and found normal CAG repeats varying from 16 to 33 units. The percentage of heterozigocity of the normal allele in the control population was 88%. In conclusion, our results showed that not all patients with the "HD" phenotype carried the expansion at the IT15 gene. Furthermore, molecular diagnosis was possible in all individuals, since no alleles of intermediate size were found. Therefore, molecular confirmation of the clinical diagnosis in HD should be sought in all suspected patients, making it possible for adequate genetic counseling.

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Subacute Sclerosing Panencephalitis (SSPE) in Toddlers and Young Children: A Case Series

Bangladesh Journal of Child Health ◽

10.3329/bjch.v44i2.51137 ◽

2020 ◽

Vol 44 (2) ◽

pp. 114-117

Author(s):

Sarah Alam ◽

Narayan Chandra Saha ◽

Seikh Azimul Hoque ◽

Chowdhury Muhammad Fuad Galib ◽

Yamin Shahriar Chowdhury

Keyword(s):

Measles Virus ◽

Clinical Presentation ◽

Neurodegenerative Disorder ◽

Past History ◽

Vegetative State ◽

Subacute Sclerosing Panencephalitis ◽

Disease Onset ◽

Case Series ◽

History Of ◽

Criteria For Diagnosis

SSPE is a neurodegenerative disorder caused by persistent defective or mutant measles virus. The disease has a gradual progressive course leading to death within 1-3 yrs or even early. SSPE is a disease of childhood and early adolescence. The classic age at presentation is 8-11 years and usually occurs after a latent period of average 6 years. Here we report 3 cases of SSPE in toddlers. Diagnosis was made on the basis of clinical presentation, EEG pattern and elevated CSF anti measles antibody titer as described in Dykan criteria for diagnosis of SSPE. Clinical presentation was very early with a relatively shorter latency and fatal progression. Two patients had past history of measles and all patients were immunized against measles. One patient died within 4 months of disease expression and 2 patients went into vegetative state within 3 months of disease onset. Bangladesh J Child Health 2020; VOL 44 (2) :114-117

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Parents' long-term adjustment to the genetic test results of minors at risk for Long QT Syndrome

PsycEXTRA Dataset ◽

10.1037/e524332011-015 ◽

2004 ◽

Author(s):

K. S. W. H. Hendriks ◽

F. J. M. Grosfeld ◽

A. A. M. Wilde ◽

J. van den Bout ◽

I. M. van Langen ◽

...

Keyword(s):

At Risk ◽

Long Qt Syndrome ◽

Genetic Test ◽

Test Results ◽

Long Qt ◽

Genetic Test Results ◽

Qt Syndrome

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Supplemental Material for Behavioral Impact of Return of Genetic Test Results for Complex Disease: Systematic Review and Meta-Analysis

Health Psychology ◽

10.1037/hea0000683.supp ◽

2018 ◽

Keyword(s):

Systematic Review ◽

Complex Disease ◽

Genetic Test ◽

Meta Analysis ◽

Test Results ◽

Genetic Test Results ◽

Behavioral Impact

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Metagnosis

10.1093/oso/9780197510766.001.0001 ◽

2020 ◽

Author(s):

Danielle Spencer

Keyword(s):

Real World ◽

Genetic Test ◽

Narrative Medicine ◽

Test Results ◽

Diagnostic Categories ◽

Genomic Knowledge ◽

Blade Runner ◽

Genetic Test Results ◽

Scant Attention ◽

Productive Model

This book identifies and names the phenomenon of metagnosis: the experience of newly learning in adulthood of a long-standing condition. It can occur when the condition has remained undetected (e.g., colorblindness) and/or when the diagnostic categories themselves have shifted (e.g., ADHD). More broadly, it can occur with unexpected revelations bearing upon selfhood, such as surprising genetic test results. This phenomenon has received relatively scant attention, yet learning of an unknown condition is frequently a significant and bewildering revelation, subverting narrative expectations and customary categories. In addressing the topic this book deploys an evolution of narrative medicine as a robust research methodology comprising interdisciplinarity, narrative attentiveness, and creating a writerly text. Beginning with the author’s own experience of metagnosis, it explores the issues it raises—from communicability to narrative intelligibility to different ways of seeing. Next, it traces the distinctive metagnostic narrative arc through the stages of recognition, subversion, and renegotiation, discussing this trajectory in light of a range of metagnostic experiences, from Blade Runner to real-world midlife diagnoses. Finally, it situates metagnosis in relation to genetic revelations and the broader discourses concerning identity. Proposing that the figure of blindsight—drawn from the author’s metagnostic experience—offers a productive model for negotiating such revelations, the book suggests that better understanding metagnosis will not simply aid those directly affected but will also serve as a bellwether for how we will all navigate advancing biomedical and genomic knowledge, and how we may fruitfully interrogate the very notion of identity.

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Solutions for Unexpected Challenges Encountered when Integrating Research Genomics Results into the EHR

ACI Open ◽

10.1055/s-0040-1719059 ◽

2020 ◽

Vol 04 (02) ◽

pp. e132-e135

Author(s):

Luke V. Rasmussen ◽

Christin Hoell ◽

Maureen E. Smith ◽

Rex Chisholm ◽

Justin Starren ◽

...

Keyword(s):

Genetic Research ◽

Lessons Learned ◽

Return Of Results ◽

Patient Portal ◽

Test Results ◽

Research Results ◽

Genetic Test Results ◽

Future Return ◽

New Research ◽

Genetic Results

Abstract Background While there have been published reports detailing technical challenges of incorporating genetic test results into the electronic health record (EHR) with proposed solutions, less has been published about unanticipated sociotechnological or practical communication challenges involved in this process. Objectives This study was aimed to describe unanticipated issues that arose returning genetic research results through the EHR as part of the National Human Genome Research Institute (NHGRI)-funded electronic Medical Records and Genomics (eMERGE) 3 consortium, and provide lessons learned for future implementations Methods We sequenced 3,000 participants on a 109-gene panel and returned genetic results initially in person and/or by letter, with a later release directly into the EHR and patient portal. Results When results were returned through the EHR, multiple participants expressed confusion and contacted the health system, resulting in our institution temporarily freezing our return of research results. Discussion We determined the likely causes of this issue to be (1) the delay between enrollment and results return, (2) inability to personalize mass e-mail messages announcing new research test results in the EHR, (3) limited space for description of test results in the EHR, and (4) the requirement to list an ordering physician for research results in the EHR. For future return of results, we propose sending preparatory e-mails to participants, including screenshots of how they can expect to see their results presented in the EHR portal. Conclusion We hope our lessons learned can provide helpful guidance to other sites implementing research genetic results into the EHR and can encourage EHR developers to incorporate greater flexibility in the future.

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The Skeletal Muscle Emerges as a New Disease Target in Amyotrophic Lateral Sclerosis

Journal of Personalized Medicine ◽

10.3390/jpm11070671 ◽

2021 ◽

Vol 11 (7) ◽

pp. 671

Author(s):

Oihane Pikatza-Menoio ◽

Amaia Elicegui ◽

Xabier Bengoetxea ◽

Neia Naldaiz-Gastesi ◽

Adolfo López de Munain ◽

...

Keyword(s):

Skeletal Muscle ◽

Amyotrophic Lateral Sclerosis ◽

Muscle Tissue ◽

Motor Neurons ◽

Neurodegenerative Disorder ◽

Disease Onset ◽

Fine Tuning ◽

Current State ◽

The Central Nervous System ◽

Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that leads to progressive degeneration of motor neurons (MNs) and severe muscle atrophy without effective treatment. Most research on ALS has been focused on the study of MNs and supporting cells of the central nervous system. Strikingly, the recent observations of pathological changes in muscle occurring before disease onset and independent from MN degeneration have bolstered the interest for the study of muscle tissue as a potential target for delivery of therapies for ALS. Skeletal muscle has just been described as a tissue with an important secretory function that is toxic to MNs in the context of ALS. Moreover, a fine-tuning balance between biosynthetic and atrophic pathways is necessary to induce myogenesis for muscle tissue repair. Compromising this response due to primary metabolic abnormalities in the muscle could trigger defective muscle regeneration and neuromuscular junction restoration, with deleterious consequences for MNs and thereby hastening the development of ALS. However, it remains puzzling how backward signaling from the muscle could impinge on MN death. This review provides a comprehensive analysis on the current state-of-the-art of the role of the skeletal muscle in ALS, highlighting its contribution to the neurodegeneration in ALS through backward-signaling processes as a newly uncovered mechanism for a peripheral etiopathogenesis of the disease.

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A Case of Familial Creutzfeldt-Jakob Disease Presenting with Dry Cough

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100005072 ◽

2006 ◽

Vol 33 (2) ◽

pp. 243-245 ◽

Cited By ~ 3

Author(s):

Sandrine Larue ◽

Steve Verreault ◽

Peter Gould ◽

Michael B. Coulthart ◽

Catherine Bergeron ◽

...

Keyword(s):

Clinical Presentation ◽

Mutation Screening ◽

Disease Onset ◽

Visual Hallucinations ◽

Progressive Dementia ◽

Gene Encoding ◽

Progressive Ataxia ◽

Persistent Cough ◽

Jakob Disease ◽

Classical Triad

ABSTRACT:Background:Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is based on the classical triad of rapidly progressive dementia, myoclonus and abnormal EEG. The 200k mutation within the gene encoding PrP, located on the short arm of chromosome 20, accounts for more than 70% of families with CJD worldwide.Case Report:Herein, we report a patient who developed persistent dry cough and classical signs of CJD, including severe cognitive decline, cerebellar signs, and myoclonic jerks, leading to death a few weeks after disease onset. Mutation screening showed that he had the 200k point mutation in the PRNP gene. His mother had died twenty years earlier with neuropathologically confirmed CJD. She had presented a rapidly progressive ataxia with myoclonus, dementia, visual hallucinations, and the same persistent dry cough.Conclusions:The clinical presentation of this familial CJD case with persistent dry cough is quite unusual. Therefore, a neurological etiology should be sought when confronted with an unexplained persistent cough.

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