eMedicine Specialties > Physical Medicine and Rehabilitation > Disorders of the Motor Unit

Kugelberg Welander Spinal Muscular Atrophy

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
Coauthor(s): Stephanie E Vallee, MS, Certified Genetic Counselor, Dartmouth-Hitchcock Medical Center, Children's Hospital at Dartmouth; Michael Dichiaro, MD, Chief Resident, Department of Physical Medicine and Rehabilitation, University of Colorado at Denver Health Sciences Center; Mary Louise Caire, MD, Consulting Staff, Department of Physical Medicine and Rehabilitation, Wise Regional Medical Center; Stephen Kishner, MD, Residency Program Director, Professor of Clinical Medicine, Department of Medicine, Section of Physical Medicine and Rehabilitation, Louisiana State University School of Medicine
Contributor Information and Disclosures

Updated: Jul 29, 2008

Introduction

Background

Spinal muscular atrophies (SMAs) represent a rare group of inherited disorders that cause progressive degeneration of the anterior horn cells of the spinal cord. The exact cause of the degeneration is unknown. Loss of these cells results in a progressive lower motor neuron disease that has no sensory involvement and that is manifested as hypotonia, weakness, and progressive paralysis. Kugelberg Welander spinal muscular atrophy (also known as Wohlfart-Kugelberg-Welander syndrome or mild SMA) is a milder form of SMA, with symptoms typically presenting after age 18 months.^1,2,3

SMAs were first described in the 1890s, by Guido Werdnig, a physician from the University of Vienna, in his lecture "On a Case of Muscular Dystrophy with Positive Spinal Cord Findings." Soon after, Professor Johann Hoffmann from Heidelberg University presented a paper describing a syndrome of progressive atrophy, weakness, and death during the early childhood period of siblings with genetically normal parents. Both physicians conducted autopsies on their patients and found severe atrophy of the ventral roots of the spinal cord. They also found histologic evidence of loss of motor neurons in the anterior horn cells of this region. Hoffmann called the syndrome spinale muskelatrophie (spinal muscular atrophy).

In the early 1960s, Byers and Banker classified SMA into categories based on the severity and age of onset of the symptoms, in an effort to predict prognosis. Their system, summarized below, became the basis for the most widely recognized system now used for the classification of SMA.

• Type I
  • Onset of symptoms before age 6 months
  • Also known as infantile onset SMA, or Werdnig-Hoffmann disease
• Type II⁴
  • Onset of symptoms at age 6-18 months
  • Also known as chronic SMA, juvenile SMA, or intermediate SMA
• Type III⁴
  • Onset of symptoms after age 18 months, usually in late childhood or adolescence
  • Also known as Kugelberg Welander SMA, or mild SMA

Although Byers and Banker's classification system focuses on only the above 3 categories, many sources refer to a fourth type of SMA.

• Type IV
  • This category is reserved for onset of symptoms during early adulthood.
  • This disorder usually carries a much more favorable prognosis than do the other types of SMA.

This article focuses only on SMA types III and IV.

Related eMedicine topics:
Focal Muscular Atrophies
Spinal Muscle Atrophy
Spinal Muscular Atrophy

Related Medscape topic:
Resource Center Spinal Disorders

Pathophysiology

Spinal muscular atrophy (SMA) is caused by successive motor unit degeneration. Muscle atrophy, caused by a progressive loss of the anterior horn cells in the spinal cord, is universal. The motor nuclei in the lower brainstem, usually those of cranial nerves V-XII (V, VII, IX, XII), also may be involved. Various stages of degeneration can be observed histologically at these sites. As the nerve cells decrease in number, replacement gliosis, pyknosis, and secondary Wallerian degeneration in the roots and peripheral nerves are observed. These processes generally begin at the caudal end of the cord and typically are symmetrical. The lower limbs usually are affected sooner and more profoundly than are the upper limbs. This degeneration most often affects the proximal musculature before it impacts the distal. Note that, unlike in amyotrophic lateral sclerosis (ALS), no corticospinal tract involvement is seen in SMA.

Frequency

United States

Spinal muscular atrophy has an estimated incidence of 1 case per 15,000 live births. The genetic carrier prevalence is 1:80.

International

Spinal muscular atrophy has an estimated incidence of 1 case per 15,000-20,000 live births worldwide.

Mortality/Morbidity

Spinal muscular atrophy (SMA) types III and IV, unlike types I and II, are consistent with survival well into adulthood.⁵ Significant morbidity occurs from progressive weakness, and patients may frequently fall or may have difficulty with stairs. Most patients use wheelchair mobility by their fourth decade of life. Scoliosis and joint contractures are also extremely common. Morbidity associated with these conditions often can be minimized with spinal surgery, as well as with aggressive physical therapy. Respiratory failure in SMA types III and IV is not as common as in types I and II. Respiratory complaints usually can be managed medically, and mechanical ventilation seldom is necessary.^6,7,8

Race

Spinal muscular atrophy (SMA) affects all races equally.

Sex

Spinal muscular atrophy affects males and females at the same rate; however, disease progression is more severe in males.

Age

The age of onset for spinal muscular atrophy is discussed above in the Background section.

Clinical

History

• 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.

Physical

• 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.

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.

• Search for CME/CE on This Topic »