Exploring the Correlates of Intermediate CAG Repeats in Huntington Disease

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Ainhi D. Ha, MD and Joseph Jankovic, MD

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Postgraduate Medicine:

Volume 123 No. 5

Category:

Clinical Focus

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DOI: 10.3810/pgm.2011.09.2466
Abstract: Objective: To explore the clinical phenotype in individuals with huntingtin gene CAG repeat lengths between 27 and 35, a range that is termed “intermediate” and below one traditionally considered diagnostic of Huntington disease (HD). Background: The Prospective Huntington Disease At-Risk Observational Study (PHAROS) found that patients with intermediate CAG lengths overlapped with those diagnosed as HD (≥ 37 CAG repeats) on the Unified Huntington’s Disease Rating Scale (UHDRS) behavioral measures. Furthermore, several patients with intermediate CAG repeats demonstrating clinical (and pathological) evidence of HD have been reported. Methods: We reviewed all cases with intermediate CAG repeats who have presented to our clinic, as well as those reported in the literature. Results: We describe 4 patients with intermediate repeats evaluated at our center whose clinical features were highly suggestive of HD. Investigations for HD phenocopies were negative. Anticipation was demonstrated in 1 case with supportive neuropathological evidence of HD. Additionally, we describe the clinical features of 5 other patients reported in the literature. Conclusion: Individuals with huntingtin gene CAG repeats in the intermediate (27–35) range should be considered at risk for the development of HD, particularly if they have a family history of HD, whether they exhibit clinical features of the disease.

Keywords: Huntington disease, trinucleotide repeats, chorea, intermediate repeats, genetic counseling, huntingtin gene