Spinal Muscular Atrophy Questions & Answers

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9. Burglen L, Lefebvre S, Clermont O, et al. Structure and organization of the human survival motor neurone (SMN) gene. Genomicx. 1996. 32:479-482.

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11. Harding AE. Inherited neuronal atrophy and degeneration predominantly of lower motor neurons. Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 3rd ed. Philadelphia: WB Saunders; 1993. 1051-64.

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14. Hausmanowa-Petrusewicz I, Zaremba J, Borkowska J, Szirkowiec W. Chronic proximal spinal muscular atrophy of childhood and adolescence: sex influence. J Med Genet. 1984 Dec. 21(6):447-50. [QxMD MEDLINE Link].

15. Walton JN. The limp child. J Neurol Neurosurg Psychiatry. 1957 May. 20(2):144-54. [QxMD MEDLINE Link].

16. Rudnik-Schoneborn S, Forkert R, Hahnen E, et al. Clinical spectrum and diagnostic criteria of infantile spinal muscular atrophy: further delineation on the basis of SMN gene deletion findings. Neuropediatrics. 1996 Feb. 27(1):8-15. [QxMD MEDLINE Link].

17. Fenichel GM. Clinical Pediatric Neurology. 3rd ed. WB Saunders: Philadelphia; 1997. 151-74.

18. Joynt R, Griggs R. Clinical Neurology. Philadelphia: Lippincott; 1997. Vol 4: 11-5.

19. Okamoto K, Saito K, Sato T, Ishigaki K, Funatsuka M, Osawa M. [A case of spinal muscular atrophy type 0 in Japan]. No To Hattatsu. 2012 Sep. 44(5):387-91. [QxMD MEDLINE Link].

20. McShane MA, Boyd S, Harding B, et al. Progressive bulbar paralysis of childhood. A reappraisal of Fazio-Londe disease. Brain. 1992 Dec. 115 ( Pt 6):1889-900. [QxMD MEDLINE Link].

21. Kennedy WR, Alter M, Sung JH. Progressive proximal spinal and bulbar muscular atrophy of late onset. A sex-linked recessive trait. Neurology. 1968 Jul. 18(7):671-80. [QxMD MEDLINE Link].

22. Kaeser HE. Scapuloperoneal muscular atrophy. Brain. 1965 Jun. 88(2):407-18. [QxMD MEDLINE Link].

23. Kondo K, Tsubaki T, Sakamoto F. The Ryukyuan muscular atrophy. An obscure heritable neuromuscular disease found in the islands of southern Japan. J Neurol Sci. 1970 Oct. 11(4):359-82. [QxMD MEDLINE Link].

24. Rudnik-Schöneborn S, Senderek J, Jen JC, Houge G, Seeman P, Puchmajerová A, et al. Pontocerebellar hypoplasia type 1: clinical spectrum and relevance of EXOSC3 mutations. Neurology. 2013 Jan 29. 80(5):438-46. [QxMD MEDLINE Link]. [Full Text].

25. Young ID, Harper PS. Hereditary distal spinal muscular atrophy with vocal cord paralysis. J Neurol Neurosurg Psychiatry. 1980 May. 43(5):413-08. [QxMD MEDLINE Link].

26. Bertini E, Gadisseux JL, Palmieri G, 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 Jul. 33(3):328-35. [QxMD MEDLINE Link].

27. Kamoshita S, Takei Y, Miyao M, Yanagisawa M, Kobayashi S, Saito K. Pontocerebellar hypoplasia associated with infantile motor neuron disease (Norman's disease). Pediatr Pathol. 1990. 10(1-2):133-42. [QxMD MEDLINE Link].

28. Eckart M, Guenther UP, Idkowiak J, Varon R, Grolle B, Boffi P, et al. The natural course of infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1). Pediatrics. 2012 Jan. 129(1):e148-56. [QxMD MEDLINE Link].

29. Penttilä S, Jokela M, Hackman P, Maija Saukkonen A, Toivanen J, Udd B. Autosomal dominant late-onset spinal motor neuronopathy is linked to a new locus on chromosome 22q11.2-q13.2. Eur J Hum Genet. 2012 Nov. 20(11):1193-6. [QxMD MEDLINE Link]. [Full Text].

30. Rudnik-Schöneborn S, Arning L, Epplen JT, Zerres K. SETX gene mutation in a family diagnosed autosomal dominant proximal spinal muscular atrophy. Neuromuscul Disord. 2012 Mar. 22(3):258-62. [QxMD MEDLINE Link].

31. Frugier T, Nicole S, Cifuentes-Diaz C, Melki J. The molecular bases of spinal muscular atrophy. Curr Opin Genet Dev. 2002 Jun. 12(3):294-8. [QxMD MEDLINE Link].

32. Chen WJ, He J, Zhang QJ, Lin QF, Chen YF, Lin XZ, et al. Modification of phenotype by SMN2 copy numbers in two Chinese families with SMN1 deletion in two continuous generations. Clin Chim Acta. 2012 Nov 20. 413(23-24):1855-60. [QxMD MEDLINE Link].

33. Finkel RS, Crawford TO, Swoboda KJ, Kaufmann P, Juhasz P, Li X, et al. Candidate proteins, metabolites and transcripts in the Biomarkers for Spinal Muscular Atrophy (BforSMA) clinical study. PLoS One. 2012. 7(4):e35462. [QxMD MEDLINE Link]. [Full Text].

34. Anderson K, Talbot K. Spinal muscular atrophies reveal motor neuron vulnerability to defects in ribonucleoprotein handling. Curr Opin Neurol. 2003 Oct. 16(5):595-9. [QxMD MEDLINE Link].

35. Hausmanowa-Petrusewicz I, Vrbova G. Spinal muscular atrophy: a delayed development hypothesis. Neuroreport. 2005 May 12. 16(7):657-61. [QxMD MEDLINE Link].

36. Roy N, Mahadevan MS, McLean M, et al. The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell. 1995 Jan 13. 80(1):167-78. [QxMD MEDLINE Link].

37. Brahe C, Bertini E. Spinal muscular atrophies: recent insights and impact on molecular diagnosis. J Mol Med. 1996 Oct. 74(10):555-62. [QxMD MEDLINE Link].

38. [Guideline] Mercuri E, Bertini E, Iannaccone ST. Childhood spinal muscular atrophy: controversies and challenges. Lancet Neurol. 2012 May. 11(5):443-52. [QxMD MEDLINE Link].

39. Arnold WD, Kassar D, Kissel JT. Spinal muscular atrophy: diagnosis and management in a new therapeutic era. Muscle Nerve. 2015 Feb. 51 (2):157-67. [QxMD MEDLINE Link].

40. Palladino A, Passamano L, Taglia A, D'Ambrosio P, Scutifero M, Cecio MR, et al. Cardiac involvement in patients with spinal muscular atrophies. Acta Myol. 2011 Dec. 30(3):175-8. [QxMD MEDLINE Link]. [Full Text].

41. Hausmanowa-Petrusewicz I, Karwanska A. Electromyographic findings in different forms of infantile and juvenile proximal spinal muscular atrophy. Muscle Nerve. 1986 Jan. 9(1):37-46. [QxMD MEDLINE Link].

42. Krivickas LS. Electrodiagnosis in neuromuscular disease. Phys Med Rehabil Clin N Am. 1998 Feb. 9(1):83-114, vi. [QxMD MEDLINE Link].

43. Buchthal F, Olsen PZ. Electromyography and muscle biopsy in infantile spinal muscular atrophy. Brain. 1970. 93(1):15-30. [QxMD MEDLINE Link].

44. Dubowitz V. Muscle disorders in childhood. Major Probl Clin Pediatr. 1978. 16:iii-xiii, 1-282. [QxMD MEDLINE Link].

45. Spinraza (nusinersen) [package insert]. Cambridge, MA: Biogen Inc. 2016 December. Available at [Full Text].

46. A Phase 3, Randomized, Double-blind, Sham-Procedure Controlled Study to Assess the Clinical Efficacy and Safety of ISIS 396443 Administered Intrathecally in Patients With Infantile-onset Spinal Muscular Atrophy - ENDEAR trial. Presented at the British Paediatric Neurology Association (BPNA) Annual Conference in January 2017. Clinical Trials.gov identifier: NCT02193074.

47. A Phase 3, Randomized, Double-blind, Sham-Procedure Controlled Study to Assess the Clinical Efficacy and Safety of ISIS 396443 Administered Intrathecally in Patients With Later-onset Spinal Muscular Atrophy – CHERISH trial. Clinical Trials.gov identifier: NCT02292537.

48. Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW, et al. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med. 2017 Nov 2. 377 (18):1713-1722. [QxMD MEDLINE Link]. [Full Text].

49. Al-Zaidy S, Pickard AS, Kotha K, Alfano LN, Lowes L, Paul G, et al. Health outcomes in spinal muscular atrophy type 1 following AVXS-101 gene replacement therapy. Pediatr Pulmonol. 2019 Feb. 54 (2):179-185. [QxMD MEDLINE Link]. [Full Text].

50. Novartis. AveXis data reinforce effectiveness of Zolgensma in treating spinal muscular atrophy (SMA) Type 1. 2019 Apr 16. Available at https://www.novartis.com/news/media-releases/avexis-data-reinforce-effectiveness-zolgensma-treating-spinal-muscular-atrophy-sma-type-1.

51. Servais L, Baranello G, Masson R, et al. FIREFISH Part 2: efficacy and safety of risdiplam (RG7916) in infants with spinal muscular atrophy (SMA) (1302). Neurology. April 14, 2020;94 (15 suppl). Presented at the 72nd Annual meeting of the American Academy of Neurology, April 25-May 1, 2020. [Full Text].

52. Evrysdi (risdiplam) [package insert]. South San Francisco, CA: Genentech. August 2020. Available at [Full Text].

53. Kissel JT, Scott CB, Reyna SP, Crawford TO, Simard LR, Krosschell KJ, et al. SMA CARNIVAL TRIAL PART II: a prospective, single-armed trial of L-carnitine and valproic acid in ambulatory children with spinal muscular atrophy. PLoS One. 2011. 6(7):e21296. [QxMD MEDLINE Link]. [Full Text].

54. Swoboda KJ, Scott CB, Crawford TO, Simard LR, Reyna SP, Krosschell 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 Aug 19. 5(8):e12140. [QxMD MEDLINE Link]. [Full Text].

55. Wadman RI, Bosboom WM, van der Pol WL, van den Berg LH, Wokke JH, Iannaccone ST, et al. Drug treatment for spinal muscular atrophy types II and III. Cochrane Database Syst Rev. 2012 Apr 18. 4:CD006282. [QxMD MEDLINE Link].

56. Wadman RI, Bosboom WM, van der Pol WL, van den Berg LH, Wokke JH, Iannaccone ST, et al. Drug treatment for spinal muscular atrophy type I. Cochrane Database Syst Rev. 2012 Apr 18. 4:CD006281. [QxMD MEDLINE Link].

57. Fernandez-Rhodes LE, Kokkinis AD, White MJ, Watts CA, Auh S, Jeffries NO. Efficacy and safety of dutasteride in patients with spinal and bulbar muscular atrophy: a randomised placebo-controlled trial. Lancet Neurol. 2011 Feb. 10(2):140-7. [QxMD MEDLINE Link].

58. van Bruggen HW, van den Engel-Hoek L, van der Pol WL, de Wijer A, de Groot IJ, Steenks MH. Impaired mandibular function in spinal muscular atrophy type II: need for early recognition. J Child Neurol. 2011 Nov. 26(11):1392-6. [QxMD MEDLINE Link].

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60. Mesfin A, Sponseller PD, Leet AI. Spinal muscular atrophy: manifestations and management. J Am Acad Orthop Surg. 2012 Jun. 20(6):393-401. [QxMD MEDLINE Link].

61. Birnkrant DJ, Pope JF, Martin JE, et al. Treatment of type I spinal muscular atrophy with noninvasive ventilation and gastrostomy feeding. Pediatr Neurol. 1998 May. 18(5):407-10. [QxMD MEDLINE Link].

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63. Sugarman EA, Nagan N, Zhu H, Akmaev VR, Zhou Z, Rohlfs EM, et al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet. 2012 Jan. 20(1):27-32. [QxMD MEDLINE Link]. [Full Text].

64. Zerres K, Rudnik-Schoneborn S. Natural history in proximal spinal muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification of existing classifications. Arch Neurol. 1995 May. 52(5):518-23. [QxMD MEDLINE Link].

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69. Brichta L, Holker I, Haug K, Klockgether T, Wirth B. In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate. Ann Neurol. 2006 Jun. 59(6):970-5. [QxMD MEDLINE Link].

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Jeffrey Rosenfeld, MD, PhD, FAAN Professor of Neurology, Associate Chairman, Department of Neurology, Director, Neuromuscular ALS/MND Program, Medical Director, The Center for Restorative Neurology, Loma Linda University Health Systems

Jeffrey Rosenfeld, MD, PhD, FAAN is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Neurological Association, Society for Neuroscience

Disclosure: Nothing to disclose.

Carmel Armon, MD, MSc, MHS Chair, Department of Neurology, Assaf Harofeh Medical Center, Tel Aviv University Sackler Faculty of Medicine, Israel

Carmel Armon, MD, MSc, MHS is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American College of Physicians, American Epilepsy Society, American Medical Association, American Neurological Association, American Stroke Association, Massachusetts Medical Society, Sigma Xi, The Scientific Research Honor Society

Disclosure: Received research grant from: Neuronix Ltd, Yoqnea'm, Israel<br/>Received income in an amount equal to or greater than $250 from: JNS - Associate Editor. UpToDate - Author Royalties.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA Professor of Pediatrics, Neurology, Neurosurgery, and Psychiatry, Medical Director, Tulane Center for Autism and Related Disorders, Tulane University School of Medicine; Pediatric Neurologist and Epileptologist, Ochsner Hospital for Children; Professor of Neurology, Louisiana State University School of Medicine

Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, American Medical Association, American Neurological Association, Association of Military Surgeons of the US, Child Neurology Society, Southern Pediatric Neurology Society

Disclosure: Nothing to disclose.

Bryan Tsao, MD Associate Professor, Department of Neurology, Loma Linda University; Chair and Service Chief, Department of Neurology, Loma Linda University Medical Center

Bryan Tsao, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Robert J Baumann, MD Professor of Neurology and Pediatrics, Department of Neurology, University of Kentucky College of Medicine

Robert J Baumann, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society

Disclosure: Nothing to disclose.

Theresa L LaBarte, DO Resident Physician, Department of Neurology, Loma Linda University Medical Center

Theresa L LaBarte, DO is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

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