Since the development of the genetic test for Huntington disease (HD), 1 several large series have found that about 1% of patients with the HD phenotype lack the characteristic trinucleotide repeat. 2, 3 The so called ‘‘phenocopies’’of HD include dentatorubral-pallidoluysian atrophy (DRPLA), Spinocerebellar Ataxia 17 (SCA17), Huntington’s disease-like type 1 (HDL1) and type 2 (HDL2), and a variety of other heredodegenerative disorders. Our case raises the possibility that another explanation for the low number of CAG repeats in an otherwise typical case of HD is that the low limit needed for the diagnosis of HD may need to be modified. Since the initial report which characterized the HD genotype, the repeat size associated with disease has decreased from 42 to 36, about one repeat every 2 years. Although based on a large body of clinical data, there is relative paucity of information supporting the suggested low limit of 36 by clinical-pathological correlations. We are pleased that our case report4 has initiated an active dialogue about this issue and would like to take this opportunity to respond to the thoughtful comments from our colleagues.

With regard to Dr. Reynolds comments, the HD test for the proband was indeed repeated. We have reported the test that was done most recently in hopes that its conclusions were more accurate. The first time this patient had testing, the CAG repeat size in the huntingtin gene was equivalent to 28. Dr. Semaka and colleagues bring up several excellent points, but also include a fairly lengthy differential diagnosis, most of which is not relevant in this patient (tardive dyskinesia, chorea gravidarum, etc). Some of their arguments are circular; they define the genetic criteria and state that there are no existing reports of HD with less than 36 CAG repeats. We know of at least one occasion when a patient with the typical phenotype and 35 CAG repeats was submitted for publication, but rejected.