Huntington Disease
Incidence
Autosomal dominant inheritance.
Clinical Characteristics
It is an adult onset degenerative disease.Traditionally a definite diagnosis of HD was made in the presence of (1) a positive family history, consistent with autosomal dominant inheritance; (2) progressive motor disability involving both involuntary and voluntary movement; and (3) mental disturbances including cognitive decline, affective disturbances, and/or changes in personality. Chorea is the major motor sign of the disease, hence the old name \"Huntington chorea.\" These involuntary movements are continuously present during waking hours, cannot be voluntarily suppressed by the patient, and worsen during stress. Although the pattern of the movements may differ between affected patients, they occur in individual patients in a stereotypic manner. Oculomotor disturbances, apart from being among the earliest signs in the transitional phase, are present in the vast majority of affected patients. Disturbances in motor speed, fine motor control, and gait correlate with disease progression and appear to be better measures of duration of illness than chorea. The vast majority of HD patients lose weight in the course of the disease. Gait disturbances exist at least partially independently from chorea, as neuroleptic treatment that suppresses choreic movements does not improve the gait disturbance. Most patients display speech abnormalities, which are present early in the illness. Initially mild disturbance of clarity appears, which is aggravated by changes in rate and rhythm of speech as the disease progresses. Dysphagia or disturbances in swallowing generally occur late with progression of the illness. Initially, this may primarily affect intake of fluids but later will also affect intake of solids. Subcortical dementia is manifested as a global decline in cognitive capabilities ultimately present in all HD patients. In early disease, sleep is essentially normal. Choreic movements disappear during sleep. Approximately 20 percent of all patients are incontinent of urine and feces in the terminal phases of the illness, while in early symptomatic persons, incontinence rarely occurs. The diagnosis of HD is made primarily on clinical examination. Demonstration of atrophy of the caudate nucleus and the putamen by CT or MRI provide additional support. DNA testing confirm the diagnosis. Drug therapy for the management of HD is still limited to symptomatic treatment.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
DB-W, DB-F. The diagnosis of HD is made primarily on clinical examination. Demonstration of atrophy of the caudate nucleus and the putamen by CT or MRI provide additional support. A novel gene containing a trinucleotide repeat (CAG) that is expanded on HD chromosomes has been described. This highly polymorphic CAG repeat, located in the 5´ region of the Huntington gene, has been shown to range from 10 to 30 copies on normal chromosomes, while it is expanded beyond 35 repeats in HD. A finding of CAG expansion in the HD range in a symptomatic patient is further support for the diagnosis of HD. Approximately 99 percent of all patients (995 of 1007 affected persons in one series) with the clinical phenotype of HD have expansion of the CAG repeat. A significant correlation between the number of CAG repeats and the age of onset of HD was demonstrated, with earlier age of onset associated with longer repeat lengths. Therefore, in patients with signs and symptoms suggestive of HD, DNA assessment will be the single most helpful test to confirm that the patient has the molecular changes associated with HD.