Related Experiment Videos
A follow-up study of isolated cases of suspected Huntington's disease
D Bateman1, A M Boughey, F Scaravilli
1University Department of Clinical Neurology, Institute of Neurology, London, UK.
Insights
Huntington's disease (HD) can be diagnosed in 75% of patients with typical symptoms but no family history. This suggests a significant risk for their children, often due to overlooked mild cases or non-paternity.
Area of Science:
- Neurology
- Genetics
- Clinical Medicine
Background:
- Huntington's disease (HD) is a progressive neurodegenerative disorder.
- Diagnosis can be challenging in patients without a known family history of the disease.
- Sporadic cases may be misdiagnosed or attributed to other conditions.
Purpose of the Study:
- To evaluate the diagnostic accuracy of Huntington's disease in patients presenting with suggestive clinical features but no familial history.
- To determine the likelihood of HD in such cases and identify potential explanations for seemingly sporadic occurrences.
Main Methods:
- Retrospective review of 49 patients with suspected Huntington's disease and no reported affected relatives.
- Clinical assessment, including characteristic symptoms like chorea, dementia, and oculomotor abnormalities.
- Confirmation through autopsy findings, identification of affected relatives upon re-examination, or continued clinical probability.
Main Results:
- Of 32 patients with typical HD features, diagnosis was confirmed in 7 (autopsy), 5 had affected relatives, and 13 remained probable.
- In 17 patients with atypical presentations, HD was likely in 2; others had alternative diagnoses (e.g., cerebrovascular disease, tardive dyskinesia).
- The likelihood of HD in patients with typical symptoms but no family history was at least 75%.
Conclusions:
- A significant proportion of patients with typical Huntington's disease symptoms but no family history are indeed affected.
- The risk of transmission to offspring in these 'sporadic' cases is substantial, comparable to familial HD.
- Non-paternity and mild, overlooked late-onset disease in relatives are plausible explanations for seemingly sporadic Huntington's disease cases.
Abstract:
We reviewed 49 patients in whom a diagnosis of Huntington's disease (HD) seemed possible on clinical grounds, but who gave no history of definitely affected relatives. In 32 with the typical clinical features of HD (progressive chorea and dementia, postural instability, abnormal initiation of saccadic eye movements), the diagnosis was confirmed in 7 patients who had had autopsies, affected relatives were found in 5 others, and HD remained probable in a further 13 who were reexamined. In the 17 with a less typical clinical picture, a diagnosis of HD appeared most likely in 2; other causes for chorea such as cerebrovascular disease, neuroacanthocytosis, recrudescence of Sydenham's chorea, and drug-induced tardive dyskinesia could be invoked in the remainder. We conclude that the likelihood of HD in a patient with the typical clinical features of this disorder but no history of affected relatives is at least 75%, which for practical purposes implies a risk to their children hardly less than in familial HD. The most plausible explanations for seemingly sporadic patients with HD are nonpaternity and mild, late-onset disease that is overlooked by other family members.