Recent progress in the genetics of motor neuron disease.

BACKGROUND: Genetic background and pathogenesis of motor neuron diseases (MNDs) have been increasingly elucidated over recent years.

AIMS: To give an overview about publications during the last year concerning the genetic background and phenotypic manifestations of MNDs, such as familial or sporadic amyotrophic lateral sclerosis (fALS, sALS), spinal muscular atrophies (SMA), bulbospinal muscular atrophy (BSMA), and unclassified MNDs.

METHODS: Pubmed search for literature about ALS, SMA, and BSMA for the period 10/2012 to 9/2013.

RESULTS: An increasing number of mutated genes is recognised in fALS but also sALS patients. Genes mutated in sALS include C9orf72, SOD1, TARDBP, FUS, UBQL2, SQSTM1, DCTN1, and UNC13A. Juvenile (onset <20y) and adult ALS (early onset 20-60y, late onset >60y) are differentiated. Juvenile fALS is most frequently caused by mutations in ALS2, SETX, spatacsin, or Sigmar1 and adult fALS by mutations in C9orf72, SOD1, TARDBP, and FUS. Onset, phenotype, progression, and outcome of ALS are variable between different mutations, different genes, and different countries. Differentiation between sALS and fALS cases becomes artificial.

CONCLUSIONS: Further progress has been made over the last year in the clarification and understanding of the aetiology and pathogenesis of MNDs. However, further effort is needed to answer the many remaining questions.