J Med Genet 40:e69 doi:10.1136/jmg.40.5.e69
  • Online mutation report

Neuroferritinopathy in a French family with late onset dominant dystonia

  1. P F Chinnery1,2,
  2. A R J Curtis2,
  3. C Fey2,
  4. A Coulthard3,
  5. D Crompton2,
  6. A Curtis2,
  7. A Lombés4,
  8. J Burn2
  1. 1Department of Neurology, The University of Newcastle upon Tyne, UK
  2. 2Institute of Human Genetics, The University of Newcastle upon Tyne, UK
  3. 3Department of Radiology, Newcastle upon Tyne Hospitals NHS Trust, UK
  4. 4INSERM UR523, Institut de Myologie, Hôpital de La Salpêtriére, Paris, France
  1. Correspondence to:
 Dr P F Chinnery, Department of Neurology, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK; 

    We recently described a dominantly inherited movement disorder in a large family from Cumbria in the north west of England resulting from an adenine insertion at position 460–461 in the ferritin light polypeptide gene (FTL).1 The disease presented between the ages of 38 and 58 years with chorea in some subjects, focal dystonia in other subjects, and an akinetic rigid parkinsonian syndrome in others. Brain imaging showed basal ganglia cavitation that was confirmed at necropsy. Neuronal loss was accompanied by the formation of neuroaxonal spheroids, with intraneural and extraneural iron deposition. Serum ferritin levels were low in the presence of normal serum iron, transferrin and haemoglobin levels. The results of these investigations provided a direct link between a primary disorder of iron storage metabolism and a late onset neurodegenerative movement disorder.1

    Cumbria has a stable, largely white population of Anglo-Saxon and Norman origins. All of the affected subjects described in the original report lived within a 30 mile radius and were traced, using parish records, back to a probable common founder born around 1790.1 A further 10 familial cases with the same mutation were found by screening over 100 patients from northern England with undiagnosed extrapyramidal disease and a small number of other cases referred to us from other parts of the country. The nature of the mutation and our report here of a common haplotype around the gene suggested to us that neuroferritinopathy would be a rare disorder in the UK, likely to have been inherited from a single founder.

    However, a careful review of published reports identified a number of potentially similar families outside the United Kingdom, including one family from the north of France.


    Clinical features

    The French family consisted of seven subjects with dystonia as the primary clinical feature who developed symptoms between 24 …