Clinical presentation of juvenile Huntington disease

Abstract

-Objective: To describe the clinical presentation a group of patients with juvenile onset of Huntington disease. Method: All patients were interviewed following a stru c t u red clinical questioner. Patients were genotyped for the trinucleotide cytosine-adenine-guanine (CAG) repeat in the Huntington Disease gene. High resolution brain MRI was perf o rmed in all patients. Results: We identified 4 patients with juvenile onset of disease among 50 patients with Huntington disease followed prospectively in our N e u rogenetics clinic. Age at onset varied from 3 to 13 years, there were 2 boys, and 3 patients had a paternal inheritance of the disease. Expanded Huntington disease allele sizes varied from 41 to 69 trinucleotide repeats. The early onset patients presented with rigidity, bradykinesia, dystonia, dysarthria, seizures and ataxia. MRI showed severe volume loss of caudate and putamen nuclei (p=0.001) and reduced cerebral and c e rebellum volumes (p=0.01). Conclusion: 8% of Huntington disease patients seen in our clinic had juvenile onset of the disease. They did not present with typical chorea as seen in adult onset Huntington disease. There was a predominance of rigidity and bradykinesia. Two other important clinical features were s e i z u res and ataxia, which related with the imaging findings of early cortical atrophy and cerebellum volume loss.KEY WORDS: n e u rodegenerative disord e r, dynamic mutations, genotype-phenotype correlation, basal ganglia, atrophy. Apresentação clínica da forma juvenil da doença de HuntingtonRESUMO -Objetivo: D e s c rever o quadro clínico de um grupo de pacientes com forma juvenil da doença de Huntington. Método: Os pacientes foram entrevistados seguindo um questionário clínico estru t u r ado; genotipados para a repetição do trinucleotídeo citosina-adenina-guanina (CAG) no gene da doença de Huntington; e realizaram exame de RM de alta re s o l u ç ã o . Resultados: Identificamos 4 pacientes com doença de Huntington de início juvenil dentre 50 pacientes com doença de Huntington seguidos pro s p e ctivamente em nosso ambulatório de neurogenética. A idade de início variou entre 3 e 13 anos (2 meninos e 2 meninas). Três pacientes tiveram herança paterna da doença. O tamanho do alelo expandido da doença de Huntington variou entre 41 a 69 repetições de trinucleotídeos. As principais manifestações clínicas no início da doença foram rigidez, bradicinesia, distonia, disartria, crises epilépticas e ataxia. A RM mostro u acentuada atrofia dos núcleos caudado e putamem (p=0.001) e redução do volume cerebral e cere b e l a r (p=0.01). Conclusão: 8% dos pacientes com doença de Huntington acompanhados em nosso ambulatório apresentaram início juvenil da doença. Estes pacientes não apresentaram a manifestação típica de coréia o b s e rvada em adultos. Houve predomínio de rigidez, bradicinesia, crises epilépticas e ataxia, o que tem relação com a atrofia cortical e cerebelar precoce na RM.

Clinical features of Chinese patients with Huntington's disease carrying CAG repeats beyond 60 within HTT gene

“…The neuroimaging features of our four patients were similar to those reported previously (12,28). Onset with epilepsy and intellectual decline were observed in two patients and non-choreiform movements occurred in the other two patients.…”

“…Second, their manifestations were atypical, in which rigidity, bradykinesia, intellectual decline, behavior change, frequent falls, speech impairment, seizures, and ataxia were the initial or predominant (7,14,(19)(20)(21)(22)(23)(24). Fourth, the atrophies in cerebral cortex, striatum or cerebellum and increased density in T 2 -weighted signal in caudate and putamen nuclei in MRI were characteristic imaging features (12,23,28). Third, paternal transmission was predominant pattern of inheritance (19).…”

“…It is reported that the expanded CAG repeat size of juvenile-onset HD (JHD) usually exceeds 60 (10,11). But it could also be below 59 and even as low as 41 (12)(13)(14). Most of the reports focus on JHD and little concerns about the clinical features of (15,16).…”

Cerebellar lipid differences between R6/1 transgenic mice and humans with Huntington’s disease

“…All of these diseases exhibit cerebellar manifestations. Cerebellar gray and white matter volumes have been reported to be smaller in HD subjects than in control subjects (Ruocco et al. 2006; Paradiso et al.…”

Sydenham's chorea in a family with Huntington's disease: case report and review of the literature

“…Some cases have been reported in young children, but the juvenile-onset form (Westphal variant) of chorea is usually rare and the typical presentation is a "Parkinson-like" syndrome, with rigidity, ataxia, seizures, cognitive decline and a tendency towards insanity and suicide. [11][12][13] This diagnosis was ruled out in the light of the neurological manifestations and the presence of carditis. Even though a predictive genetic test is available, there is an international ethical consensus that considers that presymptomatic diagnosing of adult-onset disorders that do not have any preventive or curative treatment should only be requested or performed after obtaining fully informed consent and expression of will from capable individuals who are no longer minors.…”