Mov Disord 1998 Nov;13(6):920-8. Topper R, et al.
Westphal Variant of Huntington's Disease
The Westphal variant of Huntington's disease (HD) is a distinct clinical entity of HD characterized by a rigid-hypokinetic syndrome and is often associated with a juvenile onset of disease.
Definite genetic differences between the subtypes of HD have not been delineated so far. Here we present the results of a battery of neuro-physiological tests including somatosensory-evoked potentials, blink reflexes, long-latency reflexes, and measurement of saccadic velocities in a Westphal HD patient.
Although quantitative assessment of his motor performance showed a severe hypokinetic syndrome resembling Parkinson's disease, the results of somatosensory-evoked potentials and blink reflexes were indistinguishable from results obtained in hyperkinetic HD patients. Long-latency reflexes, however, which are typically absent in hyper-kinetic HD patients, were retained in this patient.
It is concluded that neurophysiology in HD patients is not a mere reflection of the patient's symptomatology but can give insight into the underlying patho-physiological process.
HUNTINGTON'S DISEASE
(WESTPHAL VARIANT)
DEFINITION:
A progressive neurodegenerative disorder characterized initially by bradykinesia and rigidity then choreiform movements.
EPIDEMIOLOGY:
- incidence: 5-10/100,000 (prevalance)
- age of onset:
- of patients with Huntingon's Disease
- 10% have onset of symptoms prior to 20 years of age
- 5% have onset of symptoms prior to 14 years of age
- 1% have onset of symptoms prior to 10 years of age
- risk factors:
- familial - autosomal dominant
- father is affected in 83% of cases
- chrom.#: 4p16.3
- gene: Huntington Disease (HD) gene
PATHOGENESIS:
- in Huntington's Disease:
-
the HD gene was isolated by James Gusella's group in winter
of 1993 and an unstable part of the gene was identified in the coding region characterized by numerous repeats of single trinucleotide sequences containing the basescytosine, adenine, and guanine (CAG)
-
the function the the HD gene product is unknown
2. Genetic Defect
- genetic defect -> amplification of the sequence of unstable
trinucleotide repeats (CAG) to greater than 30 -> encodes
a long tract of glutamine residues -> altered protein ->
pheno-typic expression of the disease
-
there is a strong inverse correlation between the length of
the CAG repeat and the age of onset of the disease
CLINICAL FEATURES:
1. Neurologic Manifestations
1. Initial
- initially presents with bradykinesia and rigidity
- may also initially present with behavioural or cognitive
deterioration and poor school performance
2. Late
- chorea tends to involve proximal muscle groups
- associated features
- 50% - generalized tonic-clonic seizures
- 50% - cerebellar signs
- 20% - oculomotor apraxia
- gait disturbance
- more rapid course in children than in adults
- average of 8 years till death (14 years in adults)
INVESTIGATIONS:
- identification of amplified CAG sequences in the HD gene of affected individuals
2. Imaging Studies
- atrophy of the caudate nucleus and frontal cortex
- dilatation of the lateral ventricles
MANAGEMENT:
1. Medical
- movement disorders
- bradykinesia/rigidity - antiparkinsonian drugs
- chorea - dopamine antagonists
- behavioural problems
- neuroleptics and/or antidepressants
- seizure disorder
- very resistant to anticonvulsant therapy
2. Supportive
