Huntington's disease and Huntington's disease-like syndromes: an overview

Curr Opin Neurol. 2013 Aug;26(4):420-7. doi: 10.1097/WCO.0b013e3283632d90.

Abstract

Purpose of review: The differential diagnosis of chorea syndromes may be complex and includes various genetic disorders such as Huntington's disease and mimicking disorders called Huntington's disease-like (HDL) phenotypes. To familiarize clinicians with these (in some cases very rare) conditions we will summarize the main characteristics.

Recent findings: HDL disorders are rare and account for about 1% of cases presenting with a Huntington's disease phenotype. They share overlapping clinical features, so making the diagnosis purely on clinical grounds may be challenging, however presence of certain characteristics may be a clue (e.g. prominent orofacial involvement in neuroferritinopathy etc.), Information of ethnic descent will also guide genetic work-up [HDL2 in Black Africans; dentatorubral-pallidoluysian atrophy (DRPLA) in Japanese etc.], Huntington's disease, the classical HDL disorders (except HDL3) and DRPLA are repeat disorders with anticipation effect and age-dependent phenotype in some, but genetic underpinnings may be more complicated in the other chorea syndromes.

Summary: With advances in genetics more and more rare diseases are disentangled, allowing molecular diagnoses in a growing number of choreic patients. Hopefully, with better understanding of their pathophysiology we are moving towards mechanistic therapies.

Publication types

  • Review

MeSH terms

  • Genetic Predisposition to Disease / genetics
  • Heredodegenerative Disorders, Nervous System / classification
  • Heredodegenerative Disorders, Nervous System / genetics
  • Heredodegenerative Disorders, Nervous System / physiopathology
  • Humans
  • Huntington Disease / classification
  • Huntington Disease / genetics*
  • Huntington Disease / physiopathology*
  • Iron Metabolism Disorders / genetics
  • Membrane Proteins / genetics
  • Mutation / genetics*
  • Myoclonic Epilepsies, Progressive / genetics
  • Neuroaxonal Dystrophies / genetics
  • Phenotype
  • Prions / genetics
  • Syndrome
  • TATA-Box Binding Protein / genetics

Substances

  • Membrane Proteins
  • Prions
  • TATA-Box Binding Protein
  • TBP protein, human
  • junctophilin

Supplementary concepts

  • Huntington Disease-Like Syndrome
  • Neuroferritinopathy