Genetically transmitted progressive neurologic disease
characterized by involuntary (choreiform) movements and slowly progressive
dementia, leading to death 15 to 20 years after the first clinical symptoms.
Chorea Chronica Progressiva; Chorea Chronica Progressiva
Hereditaria; Chorea Hereditaria Chronica; Chorea Progressiva Hereditaria;
Chronic Degenerative Chorea; Chorea Major; Erb Vitus Dance; Hereditary
Chorea; Huntington Disease (HD); Lund-Huntington Chorea (or Syndrome);
Microcellular Striatal Syndrome.
Neurodegenerative disorder first described in 1872 by
George Huntington of Ohio, U.S. as a progressive degenerative disorder of the
central nervous system (CNS)
of unknown etiology with involuntary movements and dementia.
Prevalence in the general population is estimated at
4-7:100,000. No sex or racial predilection. However, localized geographic
clusters of disease exist (lowest frequencies have been found in South
African blacks, individuals in Japan, and North American blacks).
Autosomal dominant with complete penetrance.
New mutations are rare. The HC gene is located on the tip of the long arm of
chromosome 4 (locus 4p16.3) and leads to increased length of a CAG triplet
repeat at the end of the mRNA. This longer repeat [46 (range 37-86) in
Huntington disease v 18 (range 9-37) in normals] leads to unstable gene and
gene products. Fully autosomal dominant and homozygotes are no more severely
affected than heterozygotes. Juvenile rigid early-onset form is usually
The disease is characterized by premature
degeneration of nerve cells. The abnormal protein product (huntingtin) of
the HC gene accumulates in selective brain cells in the basal ganglia,
particularly the caudate nucleus and putamen, which are severely damaged.
The mutant huntingtin protein causes neurodegeneration by a direct effect on
mitochondria (decrease in mitochondrial membrane potential and
depolarization at lower calcium loads). There is a general reduction in the
neuronal population in the cerebral cortex. Neurochemical analysis reveals a
decreased gamma-aminobutyric acid and acetylcholine neuronal content.
Neuropathologic changes in juvenile forms are similar to the adult-onset
forms. Marked deficiency of the mitochondrial respiratory chain in the
caudate nucleus of patients with HC, but not in the platelets, has been
Usually not made until the choreic movements are
recognized. Although nondiagnostic, in the late stages of the disease, CT
scanning of the CNS demonstrates loss of the bulge in the wall of the
lateral ventricles, which is normally caused by the head of the caudate
nucleus. Mean bifrontal-to-bicaudate ratio is decreased, indicating atrophy
of the caudate nucleus and putamen. An electroencephalogram (EEG) is not
diagnostic. A positron-emission tomography (PET) scan shows reduced glucose
uptake in the caudate nucleus preceding tissue loss and may be a valuable
indication of affection in the presumed presymptomatic period. Genetic
counseling is necessary.
Average age of onset is 35 to 55 years, but in
1% of cases the disease manifests during the first decade of life.
Affected children develop normally until 4 to 9 years of age. Early signs
include changes in behavior and personality, diminished facial expression,
and slurred speech. ...