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CHCHD10 mutations and motor neuron disease: the distribution in Finnish patients
  1. Sini Penttilä1,
  2. Manu Jokela2,
  3. Anna Maija Saukkonen3,
  4. Jari Toivanen3,
  5. Johanna Palmio1,
  6. Janne Lähdesmäki2,
  7. Satu Sandell4,
  8. Mariia Shcherbii5,
  9. Mari Auranen6,
  10. Emil Ylikallio5,
  11. Henna Tyynismaa5,
  12. Bjarne Udd1,7,8
  1. 1Neuromuscular Research Center, Tampere University and University Hospital, Tampere, Finland
  2. 2Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland
  3. 3Department of Neurology, Central Hospital of Northern Karelia, Joensuu, Finland
  4. 4Department of Neurology, Seinäjoki Central Hospital, Seinäjoki, Finland
  5. 5Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland
  6. 6Department of Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
  7. 7Folkhälsan Institute of Genetics and Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland
  8. 8Department of Neurology, Vasa Central Hospital, Vasa, Finland
  1. Correspondence to Sini Penttilä, University of Tampere, Neuromuscular Research Unit, ARVO, room F354, PL 100, 33014 University of Tampere, Finland; sini.penttila{at}uta.fi

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Introduction

Motor neuron disorders (MNDs) are a heterogeneous group of diseases that result from degeneration of motor neurons. If both upper and lower motor neurons (UMNs and LMNs) are affected, the disease is classified as amyotrophic lateral sclerosis (ALS). Primary lateral sclerosis (PLS) and progressive muscular atrophy (PMA) selectively affect the UMNs or LMNs, respectively, but are sometimes considered to be incomplete ALS variants because their phenotype may evolve into typical ALS over time. Bulbar affection in a UMN disease would favour a diagnosis of PLS over hereditary spastic paraplegia (HSP), whereas rapid progression may separate PMA from adult-onset spinal muscular atrophy (SMA).

Some SMA-like or even ALS-like phenotypes have been incorporated into the large category of sensorimotor axonal neuropathies (Charcot-Marie-Tooth disease type 2, CMT2),1 although sensory abnormalities may be subtle in some forms.2 On the other hand, spinal and bulbar muscular atrophy (Kennedy disease) is classified as a form of adult-onset SMA despite prominent sensory abnormalities. It has recently been argued that the current classification system of MNDs is unsatisfactory and should be revised to include genetically and prognostically important categories.3

We have recently identified a new form of motor neuron disease in 55 patients from 17 Finnish families, where distinctive phenotype did not match any pre-existing neuromuscular disease category.4–6 Spinal muscular atrophy Jokela type (SMAJ, OMIM #615048) is characterised by painful cramps, fasciculations, decreased or absent tendon reflexes, elevated creatine kinase and hand tremor. The first symptoms appear commonly after age 30–40. Electromyography (EMG) and muscle biopsy display widespread neurogenic findings and a proportion of patients show sensory abnormalities. Muscle weakness and atrophy appear much later in the disease course, and patients have remained ambulant for several decades and their life expectancy is within normal range.4 ,5 SMAJ is caused by a dominant …

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