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Psychiatric and Cognitive Difficulties as Indicators of Juvenile Huntington Disease Onset in 29 Patients
Pascale Ribaï, MD;
Karine Nguyen, MD;
Valérie Hahn-Barma, MD;
Isabelle Gourfinkel-An, MD, PhD;
Marie Vidailhet, MD, PhD;
Antoine Legout, MD;
Catherine Dodé, PhD;
Alexis Brice, MD;
Alexandra Dürr, MD, PhD
Arch Neurol. 2007;64(6):813-819.
Background Juvenile Huntington disease (JHD) is a rare clinical entity characterized by an age at onset younger than 20 years. Patients usually have an expansion of more than 60 CAG repeats in the Huntington disease (HD) gene, and the disease is usually inherited from the father. In general, precise age at onset is difficult to assess in HD because of insidious onset and anosognosia. Onset of motor difficulty signs is usually used to define age at onset.
Objectives To evaluate diagnosis delay in patients with JHD and to analyze the clinical and genetic features of JHD.
Design Retrospective clinical and genetic review.
Setting Referral center for HD at Salpêtrière Hospital, Paris, France.
Patients Twenty-nine patients with HD with onset before or at age 20 years who carried an abnormal CAG repeat expansion in the HD gene.
Results The mean ± SD delay before diagnosis was 9 ± 6 years (range, 0-21 years). The most remarkable signs at onset were severe psychiatric and cognitive disturbances (19 of 29 [65.5%]); rigidity was absent. Unusual signs at onset included myoclonic head tremor in 3 patients, severe isolated drug or alcohol addiction in 2, psychotic disorder in 1, and difficulty writing in 1. One patient had progressive cerebellar signs associated with cerebellar atrophy on cerebral magnetic resonance imaging before signs suggestive of HD appeared. During the course of the disease, psychiatric disturbances were severe, with at least 1 suicide attempt in 7 of 29 patients. Transmission was maternal in 25% of patients. Forty-six percent of patients with JHD had fewer than 60 CAG repeats; 6 of these patients inherited the disease from their father. Anticipation (mean ± SD, 18 ± 9 vs 25 ± 11 years; P = .27) and age at onset (mean ± SD, 17.14 ± 2.2 vs 13.29 ± 5.5 years; P = .09) was similar in patients with maternal compared with paternal transmission, respectively.
Conclusions Patients with JHD started showing disease symptoms through nonspecific features, mostly psychiatric and cognitive difficulties. This led to misdiagnosis or diagnosis delay, especially in cases without a familial history of HD. Maternal transmissions and expansions of fewer than 60 CAG repeats were unexpectedly frequent in this series and should not be considered exceptional.
Author Affiliations: Department of Genetics, Cytogenetics, and Embryology (Drs Ribaï, Nguyen, Brice, and Dürr), Fédération de Neurologie (Drs Hahn-Barma and Brice), Federative Institute for Neuroscience Research (Drs Gourfinkel-An, Vidailhet, and Brice), and Pôle d’Epileptologie Clinique (Dr Gourfinkel-An), Salpêtrière Hospital; Department of Neurology, Saint-Antoine Hospital (Dr Vidailhet); and INSERM 679, Neurology and Experimental Therapeutics (Drs Ribaï, Brice, and Dürr), Paris, France; Department of Neurology, Centre Hospitalier du Mans, Le Mans, France (Dr Legout); and Laboratoire de Biochimie et Génétique Moléculaire, Institut Cochin (Dr Dodé), and Salpêtrière Medical School, Pierre and Marie Curie University (Dr Brice), Paris, France.
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