Juvenile Huntington’s disease: two case reports and a review of the literature (original) (raw)
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Biological and clinical manifestations of juvenile Huntington's disease: a retrospective analysis
The Lancet Neurology, 2018
Background Huntington's disease is a rare, neurodegenerative disease caused by an expanded CAG repeat mutation in the huntingtin gene. Compared with adult-onset Huntington's disease, juvenile Huntington's disease (onset ≤20 years) is even rarer and has not been studied extensively. We aimed to further characterise juvenile Huntington's disease by examining the effect of CAG repeat size on disease presentation, progression, and survival. Methods We did a retrospective analysis of patients with juvenile Huntington's disease aged 20 years or younger, according to the length of their CAG repeat and who had disabling psychiatric symptoms (with motor symptoms) or motor symptoms alone, and of patients with adult-onset Huntington's disease manifesting aged 30-60 years with 40 or more CAG repeats, from the REGISTRY and ENROLL-HD platforms and from two institutional databases (Lega Italiana Ricerca Huntington Foundation and the Instituto Neurociencias de Buenos Aires and the Sanatorio de la Trinidad Mitre). Patients with psychiatric but no motor symptoms were excluded. We compared symptoms at onset and longitudinally in patients with juvenile Huntington's disease with highly expanded (HE subgroup) or low expansion (LE subgroup) mutations, grouped by hierarchical clustering analysis. We also compared disease progression (longitudinal change in Unified Huntington's Disease Rating Scale-Total Motor Score) and survival of patients with juvenile and adult-onset Huntington's disease. Findings We extracted medical records from 580 patients entered into the studies or databases between June 23, 2004, and March 31, 2018, of whom 36 patients met our definition of juvenile Huntington's disease and 197 for adult-onset Huntington's disease. According to caregiver reports, gait disturbance was more often a first presenting symptom in the HE subgroup (eight [80%] of 10 patients) than in the LE subgroup (seven [27%] of 26 patients; p=0•0071), whereas loss of hand dexterity was more common in the LE subgroup (11 [42%] of 26 patients) than in the HE subgroup (0 [0%] of 10 patients; p=0•0160). Compared with the LE subgroup, development delay (0 [0%] in the LE subgroup vs nine [90%] in the HE subgroup; p<0•0001), severe gait impairment (nine [35%] in the LE subgroup vs nine [90%] in the HE subgroup; p=0•0072), and seizures (three [11%] in the LE subgroup vs eight [80%] in the HE subgroup; p<0•0001) prevailed over time in the HE subgroup. Disease progression was more rapid in juvenile Huntington's disease (n=14) than in adult-onset Huntington's disease (n=52; generalised estimating equation model, p=0•0003). Of 121 deceased patients, median survival was shorter in the juvenile Huntington's disease (n=17) cohort than in adultonset Huntington's disease (n=104) cohort (hazard ratio 2•18 [95% CI 1•08-4•40]; p=0•002). Interpretation Patients with HE juvenile Huntington's disease differ clinically from patients with LE juvenile Huntington's disease or adult-onset Huntington's disease, suggesting reclassification of this particularly aggressive form of Huntington's disease might be required.
A case report of juvenile Huntington disease
Journal of Pediatric and Neonatal Individualized Medicine, 2017
Huntington disease (HD) is a progressive neurodegenerative disorder, characterized by autosomal dominant inheritance, movement disorder, dementia, and behavioural disturbances. It is caused by a mutation in IT15 gene on chromosome 4p16.3, which leads to unstable CAG trinucleotide repeat expansion. The onset of juvenile HD occurs before the 2 nd decade of life and comprises approximately 10% of total HD patients. Juvenile HD differs in symptomatology and is usually transmitted from paternal side with genetic anticipation phenomenon. Magnetic resonance imaging (MRI) of the brain shows specific changes of early affection of caudate nucleus and putamen. Multidisciplinary approach with symptomatic treatment of specific symptoms is the current available management. Gene editing and gene silencing treatment are under trial. Hereby, we introduce a case of an 8-year-old boy, who presented with typical symptoms of juvenile HD, positive family history with genetic anticipation phenomenon and c...
Juvenile Huntington’s Disease: A Case Report and a Review of Diagnostic Challenges
Cureus, 2023
Juvenile Huntington's Disease (JHD) is a rare variant of the hereditary neurodegenerative disorder Huntington's disease (HD). Clinical symptoms in JHD are broad and non-specific, making the initial diagnosis difficult. In this report, we describe a young Hispanic male who gradually developed cognitive decline, dystonia, and seizures. His diagnosis was delayed despite multiple visits to his pediatrician, developmental specialist, and neurologist. A history of developmental regression and unusual imaging findings prompted genetic testing, which led to the diagnosis of JHD. Though changes in the striatum on MRI are hallmarks of JHD, family and developmental history often provide the most important diagnostic clues. Careful history-taking in patients with non-specific neurological exam findings, as in patients with JHD, can prevent diagnostic delays and allow for early interventions to improve quality of life.
Neurodegenerative disease management, 2017
The symptoms of Huntington's disease are well known, yet the symptoms of juvenile Huntington's disease (JHD) are less established due to its rarity. The study examined a cluster of symptoms considered to be common, but under-recognized in JHD: pain, itching, sleeping difficulties, psychosis and tics. A symptom survey was constructed using the online tool Qualtrics and dispersed to JHD caregivers through websites. A total of 33 surveys were completed. Disrupted sleep was the most prevalent symptom (87%), followed by tics (78%), pain (69%), itching (60%) and psychosis (39%). Despite limitations, the study supports that there are symptoms in the JHD population that are not considered classic, however, are common and significant for patients and caregivers.
Managing juvenile Huntington's disease
Neurodegenerative disease management, 2013
Huntington's disease (HD) is a well-recognized progressive neurodegenerative disorder that follows an autosomal dominant pattern of inheritance. Onset is insidious and can occur at almost any age, but most commonly the diagnosis is made between the ages of 35 and 55 years. Onset ≤20 years of age is classified as juvenile HD (JHD). This age-based definition is arbitrary but remains convenient. There is overlap between the clinical pathological and genetic features seen in JHD and more traditional adult-onset HD. Nonetheless, the frequent predominance of bradykinesia and dystonia early in the course of the illness, more frequent occurrence of epilepsy and myoclonus, more widespread pathology, and larger genetic lesion means that the distinction is still relevant. In addition, the relative rarity of JHD means that the clinician managing the patient is often doing so for the first time. Management is, at best, symptomatic and supportive with few or no evidence-based guidelines. In t...
Juvenile Huntington's disease: a population-based study using the General Practice Research Database
BMJ open, 2013
The juvenile form of Huntington's disease (HD) is a rare disorder. There are no population-based estimates of either its incidence or prevalence in any population in the world. The present study was undertaken to estimate the frequency of juvenile HD in the UK and to examine the range of pharmacological treatments used in its management. The records of individuals under the age of 21 who had recorded diagnoses of HD were retrieved from the General Practice Research Database from 1990 through 2010. From these data estimates of incidence and prevalence were made as well as the specific treatments used in the treatment of its physical and psychological manifestations. 12 incident and 21 prevalent patients with juvenile HD were identified. The 21 prevalent cases included the 12 incident cases. The minimum population-based estimate of incidence is 0.70 (95% CI 0.36 to 1.22) per million patient-years. The minimum estimate of prevalence is 6.77/million (95% CI 5.60 to 8.12) per million...
Huntingtons Disease: A Case Report
Journal of Pharmaceutical Research International
Background: Huntington’s disease (HD) is a genetic neurodegenerative illness characterized by progressive nerve cell degeneration in the brain, mainly in the basal ganglia. It often manifests itself between the ages of 30 and 40. The disease is including inherited genetic genes, which means that the affected person inherits the gene from a parent who also has the same genes. In populations of western European origin, the incidence of inherited genetic diseases is 3-10 per 1,00000. In India, it is far less common. Case Presentation: This is a case of a 57 -year-old female schoolteacher who was brought to our institution with a trembling movement all over the body and imbalancing while walking. The clinical presentation of characteristics such as difficulty controlling his hands and fingers due to involuntary, uncontrolled motions is used to make the diagnosis He walked without a cane and seemed to be in good physical shape, yet when asked to sit, he slumps heavily into the chair. CT ...
Clinical diagnosis and management in early Huntington's disease: a review
Degenerative Neurological and Neuromuscular Disease, 2015
This review focuses on clinical diagnosis and both pharmacological and nonpharmacological therapeutic options in early stages of the autosomal dominant inherited neurodegenerative Huntington's disease (HD). The available literature has been reviewed for motor, cognitive, and psychiatric alterations, which are the three major symptom domains of this devastating progressive disease. From a clinical point of view, one has to be aware that the HD phenotype can vary highly across individuals and during the course of the disease. Also, symptoms in juvenile HD can differ substantially from those with adult-onset of HD. Although there is no cure of HD and management is limited, motor and psychiatric symptoms often respond to pharmacotherapy, and nonpharmacological approaches as well as supportive care are essential. International treatment recommendations based on study results, critical statements, and expert opinions have been included. This review is restricted to symptomatic and supportive approaches since all attempts to establish a cure for the disease or modifying therapies have failed so far.
Juvenile Huntington disease in Argentina
Arquivos de Neuro-Psiquiatria, 2015
We analyzed demographic, clinical and genetic characteristics of juvenile Huntington disease (JHD) and it frequency in an Argentinean cohort. Age at onset was defined as the age at which behavioral, cognitive, psychiatric or motor abnormalities suggestive of JHD were first reported. Clinical and genetic data were similar to other international series, however, in this context we identified the highest JHD frequency reported so far (19.72%; 14/71). Age at onset of JHD is challenging and still under discussion. Our findings reinforce the hypothesis that clinical manifestations, other than the typical movement disorder, may anticipate age at onset of even many years. Analyses of JHD cohorts are required to explore it frequency in populations with different backgrounds to avoid an underestimation of this rare phenotype. Moreover, data from selected populations may open new pathways in therapeutic approaches and may explain new potential correlations between HD presentations and environm...
General Hospital Psychiatry, 2012
The objective was to describe a case of juvenile Huntington's disease that first presented with seizures and psychosis. Methods: A male patient with no history of epilepsy and psychiatric disorder had his first seizure at the age of 20 years, which was followed by 3 years of psychotic disorder. Results: Laboratory investigations were normal, and mild diffuse cortical atrophy was detected using magnetic resonance imaging. Both the seizures and psychosis were difficult to treat. Three years later, chorea and personality changes appeared. Genetic tests revealed an expanded allele with 60 CAG repeats, confirming the typical Huntington's disease characteristic. Conclusion: Patients with difficult-to-treat seizures and the first episode of psychosis should be considered for the diagnosis of juvenile Huntington's disease.