Spinal muscular atrophies

Summary

The term spinal muscular atrophy (SMA) comprises a clinically and genetically heterogeneous group of diseases characterized by degeneration and loss of anterior horn cells in the spinal cord and sometimes also in the brainstem nuclei, resulting in muscle weakness and atrophy. The autosomal recessive proximal SMA (SMA 5q) is responsible for about 80 to 90% of all SMA cases and is classified according to clinical severity into the types I-III (IV). Since more than 90% of patients show a homozygous deletion of the SMN1 gene, molecular genetic testing has become the most important diagnostic tool. With increasing knowledge of other genes that cause anterior horn cell degeneration, our understanding for the pathogenesis and possible therapeutic interventions will improve. Despite promising results from genetic studies, preliminary clinical trials and experiments with animal models, a curative treatment of SMA is not yet available.

Keywords

Spinal muscular atrophy - proximal SMA - SMA plus forms - SMN1 gene - distal SMA - diagnosis

• Literatur

• 1 International SMA Consortium: Workshop report. Neuromusc Disord 1999; 09: 272-278.
• 2 Zerres K, Rudnik-Schöneborn S. Natural history in proximal spinal muscular atrophy (SMA): Clinical analysis of 445 patients and suggestions for a modification of existing classifications. Arch Neurol 1995; 52: 518-523.
• 3 Oskoui M. et al. The changing history of spinal muscular atrophy type 1. Neurology 2007; 69: 1931-1936.
• 4 Rudnik-Schöneborn S. et al. Genotype-phenotype studies in infantile spinal muscular atrophy (SMA) type I in Germany: implications for clinical trials and genetic counselling. Clin Genet 2009; 76: 168-178.
• 5 Zerres K. et al. A collaborative study on the natural history of childhood and juvenile onset proximal spinal muscular atrophy (type II and III SMA): 569 patients. J Neurol Sci 1997; 146: 67-72.
• 6 Van den Berg-Vos RM. et al. Sporadic lower motor neuron disease with adult onset: classification of subtypes. Brain 2003; 126: 1036-1047.
• 7 Gdynia HJ. et al. Classification of phenotype charactrstics in adult-onset spinal muscular atrophy. Eur Neurol 2007; 58: 170-176.
• 8 Lefebvre S. et al. Identification and characterization of spinal muscular atrophy-determining gene. Cell 1995; 80: 155-165.
• 9 Wirth B. et al. Quantitative analysis of survival motor neuron copies: identification of subtle SMN1 mutations in patients with spinal muscular atrophy, genotype-phenotype correlation, and implications for genetic counseling. Am J Med Genet 1999; 64: 1340-1356.
• 10 Lunn MR, Wang CH. Spinal muscular atrophy. Lancet 2008; 371: 2120-2133.
• 11 Lorson CL. et al. Spinal muscular atrophy: mechanisms and therapeutic strategies. Hum Mol Genet 2010; 19: R111-R118.
• 12 Feldkötter M. et al. Quantitative analyses of SMN1 and SMN2 based on real-time LightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. Am J Hum Genet 2002; 70: 358-368.
• 13 Rudnik-Schöneborn S. et al. Congenital heart disease is a feature of severe infantile spinal muscular atrophy. J Med Genet 2008; 45: 635-638.
• 14 Oprea GE. et al. Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy. Science 2008; 320: 524-527.
• 15 Prior TW. et al. A positive modifier of spinal muscular atrophy in the SMN2 gene. Am J Hum Genet 2009; 85: 408-413.
• 16 Bernal S. et al. The c.859G>C variant in the SMN2 gene is associated with types II and III SMA and originates from a common ancestor. J Med Genet 2010; 47: 640-642.
• 17 Sendtner M. Therapy development in spinal muscular atrophy. Nature Neuroscience 2010; 13: 795-799.
• 18 Swoboda KJ. et al. SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy. PLOS One 2010; 05 e12140: 1-13.
• 19 Burghes AHM, McGovern VL. Antisense oligonucleotides and spinal muscular atrophy: skipping along. Genes Dev 2010; 24: 1574-1579.
• 20 Wang CH. et al. Consensus statement of standard of care in spinal muscular atrophy. J Child Neurol 2007; 22: 1027-1049.
• 21 Nishimura AL. et al. A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Hum Genet 2004; 75: 822-831.
• 22 Zerres K, Rudnik-Schöneborn S. 93rd ENMC international workshop: non-5q-spinal muscular atrophies (SMA) – clinical picture (April 2001, Naarden, The Netherlands). Neuromuscul Disord 2003; 13: 179-183.
• 23 Bertini E. et al. Distal infantile spinal muscular atrophy associated with paralysis of the diaphragm: A variant of infantile spinal muscular atrophy. Am J Med Genet 1989; 33: 328-335.
• 24 Rudnik-Schöneborn S. et al. Long-term observations of patients with infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1). Neuropediatrics 2004; 35: 174-182.
• 25 Grohmann K. et al. Mutations in the gene encoding immunoglobulin mu-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1. Nat Genet 2001; 29: 75-77.
• 26 Chou SM. et al. Infantile olivopontocerebellar atrophy with spinal muscular atrophy (infantile OPCA + SMA). Clin Neuropathol 1990; 09: 21-32.
• 27 Barth P. Pontocerebellar hypoplasias. Brain & Developm 1993; 15: 411-422.
• 28 Renbaum P. et al. Spinal muscular atrophy with pontocerebellar hypoplasia is caused by a mutation in the VRK1 gene. Am J Hum Genet 2009; 85: 281-289.
• 29 Rudnik-Schöneborn S. et al. Extended phenotype of pontocerebellar hypoplasia with infantile spinal muscular atrophy. Am J Med Genet 2003; 117A: 10-17.
• 30 Borochowitz Z. et al. Infantile spinal muscular atrophy (SMA) and multiple bone fractures in sibs: a lethal new syndrome. J Med Genet 1991; 28: 345-348.
• 31 Greenberg F. et al. X-linked infantile spinal muscular atrophy. Am J Dis Child 1988; 142: 217-219.
• 32 Ramser J. et al. Rare missense and synonymous variants in UBE1 are associated with X-linked infantile spinal muscular atrophy. Am J Hum Genet 2008; 82: 188-193.
• 33 Walter MC. et al. Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of adultonset, dominant myopathies are associated with the desmin mutation R350P. Brain 2007; 130: 1485-1496.
• 34 Auer-Grumbach M. et al. Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HSSN2C. Nat Genet 2010; 42: 160-164.
• 35 Irobi J. et al. Unraveling the genetics of distal hereditary motor neuropathies. Neuromolecular Med 2006; 08: 131-146.
• 36 Dierick I. et al. Relative contribution of mutations in genes for autosomal dominant distal hereditary motor neuropathies: a genotype-phenotype correlation study. Brain 2008; 131: 1217-1227.
• 37 Hirayama K. et al. Juvenile muscular atrophy of unilateral upper extremity: A new clinical entity. Psychiatria Neurol Jpn 1959; 61: 2190-2197.
• 38 Elsheikh B. et al. Spinal angiography and epidural venography in juvenile muscular atrophy of the distal arm “Hirayama disease”. Muscle Nerve 2009; 40: 206-212.
• 39 Rhodes LE. et al. Clinical features of spinal and bulbar muscular atrophy. Brain 2009; 132: 3242-3251.
• 40 Mariotti C. et al. Phenotypic manifestations associated with CAG-repeat expansion in the androgen receptor gene in male patients and heterozygous females: a clinical and molecular study of 30 families. Neuromuscul Disord 2000; 10: 391-397.