KUGELBERG-WELANDER DISEASE
 
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    KUGELBERG-WELANDER DISEASE

     

    DEFINITION:

    A neurological disorder characterized by degeneration of the anterior horn cells of the spinal cord resulting in proximal muscle weakness.

    EPIDEMIOLOGY:

    • incidence: ?
    • age of onset:
      • after 2 years of age -> adulthood
    • risk factors:
      • familial - autosomal recessive
        • chrom. #: 5
        • gene: neuronal apoptotic inhibitor protein (NAIP)
      • M = F

    PATHOGENESIS:

    1. Background

    • the Spinal Muscular Atrophies (SMA) are a group of inherited disorders in which there is degeneration of the anterior horn cells in the spinal column resulting in weakness
    • there are 3 clinical variants based on varying degrees of severity and onset:
      • Type I - Infantile Type - Werdnig-Hoffmann Disease (Severe)
      • Type II - Intermediate Form (Intermediate)
      • Type III - Juvenile Type - Kugelberg-Welander Disease (Mild)
    • SMA may be a polygenic disorder as a second gene has been identified adjacent to the NAIP gene on chromosome 5 and it is hypothesized that the protein products of these two genes interact to form a neuronal apoptotic factor; therefore a mutation in either gene may cause the disease
    • apoptosis means programmed natural cell death and NAIP may act as an inhibitor of programmed neuronal cell death

    2. Genetic Defect

    • genetic defect -> NAIP is unable to stop the programmed neuronal death of anterior horn cells -> premature death of anterior horn cells -> muscle weakness

    CLINICAL FEATURES:

    1. Neurological Manifestations

    1. Muscle Weakness

    1. Lower Limbs

    • proximal muscles are more involved than distal muscles
    • gross motor development delay or regression
    • positive Gower's sign
    • abnormal gait - waddling, flat-footed, and wide based
    • difficulty with running, climbing steps, and jumping
    • everted posture of the feet
    • wasting of the lower legs

    2. Upper Limbs

    • less affected than the lower limbs
    • hand tremor with outstretched arms

    2. Others

    • fasciculations of the tongue
    • joint hypermobility
    • scoliosis
    • normal intelligence, facial movements, sensation, and sphincter function

    INVESTIGATIONS:

    1. Diagnostic

    • atrophy of the anterior horn cells on autopsy
    • ? identification of mutations in the NAIP gene (or adjacent gene) in affected patients

    2. Serum

    • normal or moderately elevated CPK

    3. Muscle Biopsy

    • widespread atrophy involving all fibre types with groups of normal or enlarged type 1 fibres
    • fibre type grouping with focal small group atrophy

    4. Electrophysiological Studies

    1. EMG

    • patterns consistent with denervation and reinnervation

    2. Motor Nerve Conduction Velocity

    • normal

    MANAGEMENT:

    1. Supportive

    • no treatment for the underlying disorder
    • multidisciplinary approach:
      • Paediatrics, Neurology, Orthopedics, Physiotherapy
      • genetic counselling
    • ankle-foot orthoses or calipers for ambulation

    2. Experimental

    1. Gene Therapy

    • delivery of the NAIP gene to the anterior horn cells via genetically-engineered polio virus vectors

    3. Prognosis

    • able to stand and walk unaided
    • weakness is usually static but can also be slowly progressive or lessen with age
    • usually a normal life span but long term survival usually depends upon the respiratory function

     

     

    Pediatric Database - KUGELBERG-WELANDER DISEASE

     

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