Article Text

PDF
British Neuropsychiatry Association 2012 – AGM
A1 Differential diagnosis in relation to Huntington's disease
  1. D Martino

Abstract

Davide Martino, Honorary Clinical Lecturer in Neurology, PhD, MD. University of Bari, Italy: MD 1999 Medicine; Specialist Training 2004 Neurology; PhD in Neuroscience 2008, Clinical Neuroscience. Research/professional experience: 1993–1994: Internship, Institute of Biological Chemistry, Medical Faculty, University of Bari, Italy. 1996–1999: Internship, Neurological University Clinic, Policlinico Hospital, Bari, Italy. 1999–2004: Specialist Registrar in Neurology, Neurological University Clinic, Policlinico Hospital, Bari. April 2003 to October 2003: European Marie Curie Research Fellow, Department of Neuroimmunology, Institute of Neurology, UCL, London, UK (Supervisor: Dr Gavin Giovannoni). October 2003 to June 2004 and April 2005 to June 2006: Research Fellow, Department of Neuroimmunology, Institute of Neurology, UCL, London, UK (Supervisor: Dr Gavin Giovannoni). April 2003 to June 2004 and April 2005 to June 2006: Honorary Clinical Assistant, National Hospital for Neurology & Neurosurgery, London, UK (Supervisors: Professor Kailash P, Bhatia, Professor Niall P Quinn). April 2005 to June 2006: Research Fellow, Sobell Department of Motor Neuroscience, Institute of Neurology, UCL, London, UK (Supervisors: Professor Kailash P, Bhatia, Professor Niall P Quinn). 2004–2008: PhD in Applied Neuroscience, Department of Neurological and Psychiatric Sciences, University of Bari, Italy (Supervisor: Professor Giovanni Defazio). July 2008 to July 2010: Grantee of a Research Assistant Bursary, Department of Neurological and Psychiatric Sciences, University of Bari, Italy. September 2010 to May 2011: Winner of comparative evaluation in September 2010 for a Senior Lecturer position (Ricercatore) in Neurology at the University of Bari, Italy (post currently held in standby, due to financial restrictions imposed by the central Italian government to public universities). Temporary contract as post-doctoral research fellow and clinical assistant at the Department of Neurological and Psychiatric Sciences, University of Bari. May 2011, present: Honorary Clinical Lecturer, Neuroscience & Trauma Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University London. Locum Consultant in Neurology, Neurology Department, Princess Royal University Hospital (Farnborough Common, Orpington).

The history of Huntington's disease-like (HDL) syndromes begins with the identification of the Huntington's disease (HD) gene in 1993, one of the first major achievements in molecular neurogenetics. Between 1% and 8% of patients with a clinical phenotype of HD, however, do not have the typical causative IT15 gene expansion. These conditions may represent look-alikes of the typical young adult-onset phenotype of HD, hence manifesting with generalised chorea, personality and behavioural changes, and cognitive decline; however, another relevant group of HD phenocopies is more commonly overlooked, which resembles the akinetic-rigid (Westphal) variant of HD, typically starting in childhood or peripuberal years. In the first group, spinocerebellar (SCA)-17, or HDL-4, is probably the most common in our geographical areas, accounting for 0.5%–1.8% of all HD-like presentations. Despite similarities in the pattern of inheritance to HD and the heterogeneity of clinical presentation, SCA-17 may be distinguished from HD by the marked cerebellar involvement, concurrent epilepsy, and a different pattern of eye movement abnormalities. Other HDL syndromes include HDL-2, secondary to junctophilin-3 gene mutations, which represent a quantitatively important cause of HD-like presentation among people of African ancestry and one of the most phenomenologically similar to HD, and HDL-1, which is caused by mutation in the prion protein gene. The most important HD phenocopies is characterised by dentatorubropallidoluysian atrophy, which may have a choreic, a myoclonic or an ataxic prevalent presentation. Benign hereditary chorea is a genetically heterogeneous and complex entity, often associated with lung and thyroid involvement, and in rarer adult-onset forms it may be a possible cause of the controversial concept of ‘senile chorea’. Among phenocopies of the young adult-onset phenotype of HD of recessive inheritance, Friedreich ataxia is probably the most commonly encountered. Neuroacanthocytosis syndromes should also not be overlooked, primarily chorea-acanthocytosis and the X linked McLeod syndrome (the latter characterised by a remarkably slower course). Despite the difficult confirmatory diagnosis of neuroacanthocytosis syndromes, the co-occurrence of raised creatine kinase and liver enzymes plasma levels and the presence of a peculiar movement disorder are helpful clues. Other autosomal recessive conditions that enter the differential diagnosis are ataxia with oculomotor apraxia type 1 and ataxia-teleangectasia. The phenocopies of the Westphal variant of HD include primarily autosomal recessive dystonia-parkinsonism syndromes, in most instances associated with brain metal accumulation. These comprise iron accumulation syndromes, for example, pantothenate kinase-associated neurodegeneration, PLA2G6-associated neurodegeneration, neuroferritinopathy and aceruloplasminemia, or copper accumulation as in Wilson's disease. Sporadic, non-degenerative causes of chorea occasionally mimicking HD are high in number and often are associated with systemic illnesses. The aim of this presentation is to provide an overview of the HD phenocopies, highlighting their peculiar clinical features, and then, using an inverse approach, starting from the specific clinical symptom, trying to underscore the main aspects useful in the differential diagnosis.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.