engleski

Speech and Language Delay as Early Manifestations of Juvenile Huntington's Disease

Introduction. Huntington’ s disease (HD) is caused by a CAG repeat mutation translating as a polyglutamine expansion in the huntingtin protein, whose main pathogenic mechanism is a gain of toxic function. The clinical features of Juvenile Huntington’ s Disease (JHD) typically defined as onset of symptoms by an age less than 20 years, usually paternal inheritance and large expansions beyond 60 CAG repeats is estimated to comprise 5-7% of all HD patients. Less than 1% of all HD affected persons present before age of 10 years with symptoms markedly different from more common adult-onset. Classical juvenile pathology is characterized by rigidity, early cognitive decline, myoclonus and seizures. We report rather unusual juvenile onset of the disease in one 8 year-old boy who presented with a history of speech impairment starting after the age of 3 years. Last not least it should be to point out the necessity of better information of andrologists /gynaecologists about HD in treating couples with male reduced fertility. Methods. Family history ; clinical study of child and his father ; father’ s CT and child’ s MRI of brain ; molecular analysis of deceased father and affected son with clinical follow up during last 28 months. Results. Molecular analysis of 34-year-old father with classical HD symptoms including dysarthric speech 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 and lesions in the basal ganglia were found on MRI. It seems that speech delay predated motor symptoms by at least 2 to 3 years even child was rather “ clumsy” since very beginning. During last four years discrete ataxic gait and bradykinesia have progressed to rigidity, frequent myoclonus, and impossibility to walk at the age of 7years and 5 months. Conclusion. Speech and language delay present in our proband may be an early feature of JHD that can precede motor symptoms. These findings highlight the importance of screening for speech delay in sibs with a family history of HD. The diagnosis of JHD is difficult to make and differs from that in adults both with respect to clinical presentation and the timing of the decision to proceed with molecular genetic testing because for ethical and psychosocial reasons, genetic testing of presymptomatic children is not common. In described family evident anticipation with paternal imprinting in four generation studied HD family permitted early recognition of diagnosis. Molecular analysis in the son and the father confirms close correlation between size of CAG expansion with clinical features and disease’ s progression.

juvenile Huntington's disease; speech delay; paternal imprinting

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