title: Madras motor neuron disease (MMND) is distinct from the riboflavin transporter genetic defects that cause Brown-Vialetto-Van Laere syndrome.
abstract: BACKGROUND
  Madras motor neuron disease (MMND), MMND variant (MMNDV) and Familial MMND (FMMND) have a unique geographic distribution predominantly reported from Southern India. The characteristic features are onset in young, weakness and wasting of limbs, multiple lower cranial nerve palsies and sensorineural hearing loss. There is a considerable overlap in the phenotype of MMND with Brown-Vialetto-Van Laere syndrome (BVVL) Boltshauser syndrome, Nathalie syndrome and Fazio-Londe syndrome. Recently a number of BVVL cases and families have been described with mutations in two riboflavin transporter genes SLC52A2 and SLC52A3 (solute carrier family 52, riboflavin transporter, member 2 and 3 respectively).
  
  
  RESULTS
  We describe six families and four sporadic MMND cases that have been clinically characterized in detail with history, examination, imaging and electrophysiological investigations. We sequenced the SLC52A1, SLC52A2 and SLC52A3 in affected probands and sporadic individuals from the MMND series as well as the C9ORF72 expansion. No genetic defects were identified and the C9ORF72 repeats were all less than 10.
  
  
  CONCLUSIONS
  These data suggest that MMND is a distinct clinical subgroup of childhood onset MND patients where the known genetic defects are so far negative. The clinico-genetic features of MMND in comparison with the BVVL group of childhood motor neuron diseases suggest that these diseases are likely to share a common defective biological pathway that may be a combination of genetic and environmental factors.
authors.affiliation: Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India. Electronic address: atchayaramnal@yahoo.co.in.
authors.forename: Atchayaram
authors.initials: A
authors.lastname: Nalini
authors.forename: Amelie
authors.initials: A
authors.lastname: Pandraud
authors.forename: Kin
authors.initials: K
authors.lastname: Mok
authors.forename: Henry
authors.initials: H
authors.lastname: Houlden
mesh_terms: D000293:Adolescent; D000328:Adult; D010244:Bulbar Palsy, Progressive / Q000235:genetics*; D002648:Child; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D016472:Motor Neuron Disease / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*
chemical_list: D026901:Membrane Transport Proteins; D043562:Receptors, G-Protein-Coupled; C540350:SLC52A2 protein, human; C548553:SLC52A3 protein, human
keywords: BVVL; Brown–Vialetto–Van Laere syndrome; C9ORF72; MMND; Madras motor neuron disease; Riboflavin receptors