Clinical and genetic characteristics of non-Asian dentatorubral-pallidoluysian atrophy: A systematic review

Mov Disord. 2009 Aug 15;24(11):1636-40. doi: 10.1002/mds.22642.

Abstract

Dentatorubral-pallidoluysian atrophy (DRPLA) is an inherited neurodegenerative disorder regarded as found almost exclusively among the Japanese. We have performed as systematic review of published literature to investigate the clinical and genetic characteristics of non-Asian DRPLA. We identified 183 non-Asian patients in 27 families reported with DRPLA with a variable level of clinical information. Mean age at onset was 31 (range 1-67) with epilepsy, ataxia, and chorea common presenting features. A highly significant relationship was identified between repeat length and age at onset with repeat length accounting for 62% of the observed variation in age at onset (P < 0.0001). In addition, a highly significant relationship between repeat length and main presenting complaint was identified (P < 0.001). There was evidence of marked anticipation with a median intergenerational reduction in age at onset of 19 years with a corresponding increase of five repeats per generation. DRPLA is not exclusively found among the Japanese but has been reported worldwide. As such, DRPLA should be considered in the differential diagnosis of a wide spectrum of neurological disease, particularly if there is a dominant family history. Non-Asian DRPLA clinico-genetic phenomenology are similar to Asian series and our study confirms marked genetic anticipation together with a clear association between repeat length and clinical phenotype and disease severity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Anticipation, Genetic
  • Black or African American / genetics
  • Child
  • Child, Preschool
  • Diagnosis, Differential
  • Female
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Myoclonic Epilepsies, Progressive / ethnology
  • Myoclonic Epilepsies, Progressive / genetics*
  • Nerve Tissue Proteins / genetics*
  • Phenotype
  • Trinucleotide Repeats
  • White People / genetics
  • Young Adult

Substances

  • Nerve Tissue Proteins
  • atrophin-1