engleski

Juvenile huntington disease (JHD) presenting as progressive speech impairement

Huntington disease (HD) is an autosomal dominant, lethal neurodegenerative disorder of the central nervous system. It is caused by an uncontrolled expansion of a CAG dynamic mutation in the coding region of the IT 15gene. CAG repeat is translating as a polyglutamine expansion in the huntingtin protein, whose main pathogenic mechanism is a gain of toxic function. In the case of large expansion beyond 60 repeats onset may result in JHD. Although a majority of patients have a midlife onset of symptoms, in a small number of patients ( 10%) disease can manifests before 20 years of age as early onset or JHD. In adults, HD is mainly characterized by involuntary movements, cognitive decline, and behavioral disorders leading to functional disability and dementia. In contrast to patients with adult onset, in which chorea is the major motor abnormality, children often present with spasticity, rigidity, and significant intellectual decline associated with more progressive course. The earlier onset is often associated with a paternal transmission of the disease allele to the offspring. We report here a rather unusual juvenile onset of the disease in a little boy who presented with a history of speech impairment starting at the age of 4 years. During three years discrete ataxic gait and bradykinesia have progressed to rigidity, frequent myoclonus, and impossibility to walk and speak. A paucity of literature with JHD patients presenting early in life as dysarthria has initiated us to present a case report of one 7 years 5 months of age boy followed up during three last years. Last not least to point out the necessity of better information of andrologists /gynecologists about HD in case of male reduced fertility. Family study ; CT and MRI of brain ; molecular analysis of deceased father and affected son ; clinical follow up. Molecular analysis of father demonstrated 43 triplet repeats on one allele and 25 on the other. The son had 19 and 99 CAG repeats, respectively. A marked cerebellar atrophy, a progressive cortical-subcortical atrophy and lesions in the basal ganglia were found on MRI. Evident anticipation with paternal imprinting in four generation studied HD family. Molecular analysis in the son and the father confirms close correlation between size of CAG expansion with clinical features and disease’ s progression. JHD should be considered in small children suffering from progressive speech impairment.

juvenile Huntington disease; speech impairement; anticipation; imprinting

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