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Genetic testing of children at risk for Huntington's disease. US Huntington Disease Genetic Testing Group
1Hennepin County Medical Center, Minneapolis, MN, USA.
Insights
Huntington's disease (HD) gene testing in children requires careful consideration. Most symptomatic children with CAG repeat expansions had a positive family history and specific clinical signs, guiding diagnosis.
Area of Science:
- Genetics
- Pediatric Neurology
- Neurodegenerative Diseases
Background:
- Huntington's disease (HD) is a progressive neurodegenerative disorder.
- Genetic testing for CAG repeat expansions in the HTT gene is crucial for HD diagnosis.
- Understanding early-onset HD symptoms in children is vital for timely intervention.
Purpose of the Study:
- To characterize the clinical and historical profiles of pediatric patients tested for Huntington's disease.
- To evaluate the utility of genetic testing for HD in children with varying symptom presentations.
- To provide guidance for physicians regarding genetic testing for HD in pediatric populations.
Main Methods:
- Retrospective review of 44 symptomatic children tested for CAG repeat expansions in the HD gene.
- Analysis of clinical data, including age of onset, symptoms, and family history.
- Correlation of genetic test results with clinical phenotypes.
Main Results:
- Thirty-three out of 44 children had confirmed CAG repeat expansions.
- All patients with expansions had a positive family history of HD.
- Early-onset HD (first decade) with >80 CAG repeats presented with specific symptoms like declining school performance, seizures, and motor deficits.
Conclusions:
- CAG repeat expansions are strongly associated with a positive family history in pediatric HD cases.
- Specific clinical features aid in identifying children likely to have HD.
- Physicians should exercise caution when ordering HD gene tests for children with atypical symptoms or no family history, as results may be normal or unrelated.
Abstract:
We reviewed 44 symptomatic children tested for CAG repeat expansions in the gene responsible for Huntington's disease (HD). Thirty-three patients had CAG repeat expansions, and 11 did not. No patient with a CAG repeat expansion had a negative family history of HD. Of the 15 patients presenting in the first decade, 12 had greater than 80 CAG repeats and a clinical profile at the time of the test that included two or more of the following: declining school performance, seizures, oral motor dysfunction, rigidity, and gait disorder. Three patients with smaller CAG repeat expansions had incomplete or atypical symptom profiles. Symptom patterns in patients presenting in the second decade were more varied but usually included behavioral and motor symptoms. Patients without CAG expansions had incomplete or atypical symptom profiles. We define the historical and clinical profiles of HD presenting in the first two decades and suggest that physicians exercise restraint in using a "diagnostic" gene test for HD in the evaluation of at-risk children with incomplete or atypical symptom profiles or no family history of HD, in whom test results are very likely to be normal or unrelated to the patient's symptoms.