Exploring the correlates of intermediate CAG repeats in Huntington disease

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.