Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Kugelberg Welander Spinal Muscular Atrophy Clinical Presentation

  • Author: Joyce L Oleszek, MD; Chief Editor: Stephen Kishner, MD, MHA  more...
 
Updated: Apr 27, 2016
 

History

See the list below:

  • Patients with spinal muscular atrophy types III and IV usually present with an insidious onset of weakness, often following a brief period of illness, such as with influenza. The illness may have required a short period of bed rest.
  • Patients most often report symptoms associated with weakness of the hip extensor and hip abductor muscles and describe difficulty climbing stairs or getting up from a seated position on the floor.
  • Some patients also may report a mild tremor and occasional, painful muscle cramps.
  • Difficulty walking or running also is reported by the patient.
  • Parents of younger patients may report delayed developmental milestones or decreased athletic abilities in their children.
  • A family history of such disorders also may be elicited.
Next

Physical

See the list below:

  • Proximal muscle weakness is seen in spinal muscular atrophy, with the pelvic girdle being more affected than the shoulder girdle. [9]
  • Patients have decreased muscle tone.
  • Patients have diminished deep tendon reflexes. Ankle reflexes, however, may be preserved until very late in the disease's progress.
  • Fasciculations may be present in the tongue or shoulder girdle muscles (especially after manual muscle testing).
  • Minipolymyoclonus, a fine, irregular tremor of the outstretched fingers, may be seen. This is the result of denervation followed by reinnervation and the asynchronous firing of restructured and enlarged motor units.
  • Calf pseudohypertrophy has occasionally been noted, but muscle wasting of affected musculature is more prominent.
  • Patients may have a positive Gower sign and a waddling gait.
  • Approximately one third of patients have facial and masseter muscle weakness.
  • Sensory examination findings are normal.
Previous
Next

Causes

The exact etiology of spinal muscular atrophy (SMA) is unknown. SMA is an inherited disorder that almost always occurs in an autosomal recessive pattern. A few cases of autosomal dominant and X-linked recessive patterns have been reported.

All forms of SMA have been linked to a gene deletion on the long arm of chromosome 5, at band 5q13. The 2 genes associated with SMA are SMN1 (survival motor neuron 1) and SMN2, which are adjacent to each other on band 5q. SMN1 is believed to be the primary disease-causing gene.[10] SMN2 differs from it by 1 C-T transition in exon 7, leading to alternate splicing and a nonfunctional protein for 70-90% of the protein produced.[11] An attenuated disease severity and a milder phenotype appears to be correlated with the presence of 3 or more copies of SMN2.

Several mechanisms have been proposed for the relationship between the SMN genes and the natural history of SMA. The SMN1 protein has been associated with the assembly of spliceosomal ribonucleoproteins, which are critical to messenger RNA processing. The SMN1 protein has also been associated with the NAIP (neuronal apoptosis inhibitory protein) gene, a gene that helps to regulate programmed cell death. Some authors have hypothesized that a deletion of the SMN gene may be related to disturbances in the metabolism of 3',5'-adenosine monophosphate. Whether or not these disturbances contribute to neuronal degeneration in SMA remains to be seen.

A study by Sedghi et al indicated that deletions in exons 4 and 5 of NAIP are related to symptom severity in SMA.[12]

Previous
 
 
Contributor Information and Disclosures
Author

Joyce L Oleszek, MD Assistant Professor, Department of Physical Medicine and Rehabilitation, University of Colorado at Denver Health Sciences Center, The Children's Hospital of Denver

Joyce L Oleszek, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation

Disclosure: Nothing to disclose.

Coauthor(s)

Mary Louise Caire, MD Consulting Staff, Department of Physical Medicine and Rehabilitation, Wise Regional Medical Center

Mary Louise Caire, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, Texas Medical Association, American Medical Association

Disclosure: Nothing to disclose.

Stephen Kishner, MD, MHA Professor of Clinical Medicine, Physical Medicine and Rehabilitation Residency Program Director, Louisiana State University School of Medicine in New Orleans

Stephen Kishner, MD, MHA is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Stephanie E Vallee, MS Certified Genetic Counselor, Dartmouth-Hitchcock Medical Center, Children's Hospital at Dartmouth

Disclosure: Nothing to disclose.

Michael Dichiaro, MD Senior Instructor, Pediatric Rehabilitation Medicine, Children's Hospital Colorado

Michael Dichiaro, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, Association of Academic Physiatrists, American Academy of Cerebral Palsy and Developmental Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

Kat Kolaski, MD Assistant Professor, Departments of Orthopedic Surgery and Pediatrics, Wake Forest University School of Medicine

Kat Kolaski, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Physical Medicine and Rehabilitation

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kishner, MD, MHA Professor of Clinical Medicine, Physical Medicine and Rehabilitation Residency Program Director, Louisiana State University School of Medicine in New Orleans

Stephen Kishner, MD, MHA is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Teresa L Massagli, MD Professor of Rehabilitation Medicine, Adjunct Professor of Pediatrics, University of Washington School of Medicine

Teresa L Massagli, MD is a member of the following medical societies: Academy of Spinal Cord Injury Professionals, American Academy of Physical Medicine and Rehabilitation, Association of Academic Physiatrists

Disclosure: Nothing to disclose.

References
  1. Bradley WG, ed. Neurology in Clinical Practice. 5th ed. Philadelphia, Pa: Butterworth-Heinemann/Elsevier; 2008.

  2. Herring JA, ed. Tachdjian's Pediatric Orthopaedics. 4th ed. Philadelphia, Pa: Saunders/Elsevier; 2008.

  3. Wang CH, Finkel RS, Bertini ES, et al. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. 2007 Aug. 22(8):1027-49. [Medline].

  4. Russman BS, Buncher CR, White M, et al. Function changes in spinal muscular atrophy II and III. The DCN/SMA Group. Neurology. 1996 Oct. 47(4):973-6. [Medline].

  5. Zerres K, Rudnik-Schöneborn S, Forrest E, 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 Feb 27. 146(1):67-72. [Medline].

  6. Ioos C, Leclair-Richard D, Mrad S, et al. Respiratory capacity course in patients with infantile spinal muscular atrophy. Chest. 2004 Sep. 126(3):831-7. [Medline]. [Full Text].

  7. Lin LC, Jong YJ. Pulmonary function assessment in patients with spinal muscular atrophy type II and type III. Acta Paediatr Taiwan. 2004 Jan-Feb. 45(1):15-8. [Medline].

  8. Muscular Dystrophy Campaign sponsored workshop: recommendation for respiratory care of children with SMA type II and III. Neuromuscular Disord. 2003. 13:184-189.

  9. Moosa A, Dubowitz V. Spinal muscular atrophy in childhood. Two clues to clinical diagnosis. Arch Dis Child. 1973 May. 48(5):386-8. [Medline]. [Full Text].

  10. Simic G. Pathogenesis of proximal autosomal recessive spinal muscular atrophy. Acta Neuropathol. 2008 Jul 16. [Medline].

  11. Mattis VB, Bowerman M, Kothary R, et al. A SMNDelta7 read-through product confers functionality to the SMNDelta7 protein. Neurosci Lett. 2008 Jun 26. [Medline].

  12. Sedghi M, Behnam M, Fazel E, et al. Genotype-phenotype correlation of survival motor neuron and neuronal apoptosis inhibitory protein genes in spinal muscular atrophy patients from Iran. Adv Biomed Res. 2014. 3:74. [Medline]. [Full Text].

  13. Ogino S, Wilson RB. Genetic testing and risk assessment for spinal muscular atrophy (SMA). Hum Genet. 2002 Dec. 111(6):477-500. [Medline].

  14. Wang CC, Chang JG, Ferrance J, et al. Quantification of SMN1 and SMN2 genes by capillary electrophoresis for diagnosis of spinal muscular atrophy. Electrophoresis. 2008 Jul. 29(13):2904-11. [Medline].

  15. Umphred DA, ed. Neurological Rehabilitation. 5th ed. St Louis, Mo: Mosby Elsevier; 2007.

  16. Madsen KL, Hansen RS, Preisler N, Thogersen F, Berthelsen MP, Vissing J. Training improves oxidative capacity, but not function, in spinal muscular atrophy type III. Muscle Nerve. 2015 Aug. 52 (2):240-4. [Medline].

  17. Rodillo E, Marini ML, Heckmatt JZ, et al. Scoliosis in spinal muscular atrophy: review of 63 cases. J Child Neurol. 1989 Apr. 4(2):118-23. [Medline].

  18. Puruckherr M, Mehta JB, Girish MR, et al. Severe obstructive sleep apnea in a patient with spinal muscle atrophy. Chest. 2004 Nov. 126(5):1705-7. [Medline]. [Full Text].

  19. Yasuma F, Kuru S, Konagaya M. Dilated cardiomyopathy in Kugelberg-Welander disease: coexisting sleep disordered breathing and its treatment with continuous positive airway pressure. Intern Med. 2004 Oct. 43(10):951-4. [Medline]. [Full Text].

  20. Merlini L, Granata C, Bonfiglioli S, et al. Scoliosis in spinal muscular atrophy: natural history and management. Dev Med Child Neurol. 1989 Aug. 31(4):501-8. [Medline].

  21. Swoboda KJ, Kissel JT, Crawford TO, et al. Perspectives on clinical trials in spinal muscular atrophy. J Child Neurol. 2007 Aug. 22(8):957-66. [Medline].

  22. Il'ina NA, Antipova RI, Khokhlov AP. [Use of lithium carbonate to treat Kugelberg--Welander spinal amyotrophy]. Zh Nevropatol Psikhiatr Im S S Korsakova. 1980. 80(11):1657-60. [Medline].

  23. Tzeng AC, Cheng J, Fryczynski H, et al. A study of thyrotropin-releasing hormone for the treatment of spinal muscular atrophy: a preliminary report. Am J Phys Med Rehabil. 2000 Sep-Oct. 79(5):435-40. [Medline].

  24. Merlini L, Solari A, Vita G, et al. Role of gabapentin in spinal muscular atrophy: results of a multicenter, randomized Italian study. J Child Neurol. 2003 Aug. 18(8):537-41. [Medline].

  25. de Groot IJ, de Witte LP. Physical complaints in ageing persons with spinal muscular atrophy. J Rehabil Med. 2005 Jul. 37(4):258-62. [Medline].

  26. Liveson JA. Peripheral Neurology: Case Studies in Electrodiagnosis. 2nd ed. Philadelphia, Pa: FA Davis; 1991.

  27. Menkes JH. Textbook of Child Neurology. 5th ed. Baltimore, Md: Williams & Wilkins; 1995.

  28. Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric Neurology: Principles and Practice. 4th ed. Philadelphia, Pa: Mosby; 2006.

  29. Ropper AH, Brown RH. Adams and Victor's Principles of Neurology. 8th ed. New York, NY: McGraw-Hill Medical; 2005.

  30. Younger DS, Gordon PH. Diagnosis in neuromuscular diseases. Neurol Clin. Feb 1 1996. 14:135-68.

  31. Zeinos M, Sampath J, Cole C, et al. Operative treatment for hip subluxations in spinal muscular atrophy. J Bone Joint Surg. 2005. 87-B:1541-4.

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.