Exploring the correlates of intermediate CAG repeats in Huntington disease.

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.