Typical vs atypical forms of Spinal Muscular Atrophy

Most neurologists, paediatricians and medical geneticists know about thetypical presentations of spinal muscular atrophy (SMA). And more specifically,the ones related to the 5q-linked autosomal recessive form of SMA likeWerdnig-Hoffmann disease or Kugelberg-Welander disease. SMA actuallypresents with different degrees of severity and motor achievements which arenot always easy to categorize clinically into the four reported subtypes (type 1to type 4) suggesting a continuum of phenotypes.Easier access to confirmatory testing of the SMN1 gene and nowadays to NGSstudies (high-throughput sequencing of a myriad of genes) recentlyhighlighted the existence of many non-5q related forms of SMA. Althoughquite rare taken individually, these variants are important to recognize sincetherapeutic options and genetic counselling vary from one syndrome toanother.Among those, Brown-Vialetto-Van Laere syndrome (BVVL) and Fazio-Londesyndrome, two forms of severe childhood bulbospinal muscular atrophy withand without associated sensorineural deafness related to mutations in tworiboflavin transporters genes, are amenable to a cheap, effective therapybased on oral supplementation of high-dose riboflavin (vitamin B2, 30mg/kg/d).