Pediatrics: Neuromuscular Disorders

Caused by an abnormality of any component of the lower motor neuron

anterior horn cell
peripheral nerve
neuromuscular junction
muscle

Frequently associated with systemic effects, as some of the pathologic changes may affect skeletal, smooth, and cardiac muscles, the brain, and mitochondria in multiple organs.

May be progressive, acquired, or hereditary.

The most common etiology is genetic. It is crucial to obtain a detailed family history and if possible to obtain diagnostic evaluation of the affected relatives.

Diagnostic evaluation of a child with suspected neuromuscular disorder:

meticulous physical examination
detailed family history
comprehensive past medical history and surgical history
request for additional laboratory and genetic data that may be costly and not readily available must be considered following ascertainment of developmentally appropriate assessment and history

THE MOST COMMON NEUROMUSCULAR DISORDERS IN INFANTS AND CHILDREN

The most common cause of referral for possible neuromuscular disorder is when the infant appears floppy. See Table 5.2-1 on Duchenne muscular dystrophy.

TABLE 5.2-1 Comparison of Duchenne Muscular Dystrophy vs. Becker Muscular Dystrophy

	Duchenne muscular dystrophy	Becker muscular dystrophy
US prevalence (est.)	15,000	2,200
Incidence rate	1/3,500 male births	Unknown
Inheritance	X-linked	X-linked
Gene location	Xp21 (reading frame shifted)	Xp21 (reading frame maintained)
Protein	Dystrophin	Dystrophin
Onset	2-6 years	4-12 years (severe BMD ) Late teenage to adulthood (mild BMD )
Severity and course	Relentlessly progressive Reduced motor function by 2-3 years Steady decline in strength Life span <35 years	Slowly progressive Severity and onset correlate with muscle dystrophin levels
Ambulation status	Loss of ambulation: 7-13 years (no corticosteroids) Loss of ambulation: 9-15 years (corticosteroids)	Loss of ambulation > 16 years
Weakness	Proximal > distal Symmetric Legs and arms	Proximal > distal Symmetric Legs and arms
Cardiac	Dilated cardiomyopathy first to second decade Onset of signs second decade	Cardiomyopathy (may occur before weakness); third to fourth decade frequent
Respiratory	Profoundly reduced vital capacity in second decade Ventilatory dependency in second decade	Respiratory involvement in subset of patients Ventilatory dependency in severe patients
Muscle size	Calf hypertrophy	Calf hypertrophy
Musculoskeletal	Contractures: ankles, hips, and knees Scoliosis: onset after loss of ambulation	Contractures: ankles and others in adulthood
CNS	Reduced cognitive ability (reduced verbal ability)	Some patients have reduced cognitive ability
Muscle pathology	Endomysial fibrosis and fatty infiltration Variable fiber size and myopathic grouping Fiber degeneration/regeneration Dystrophin: absent Sarcoglycans: secondary reduction	Variable fiber size Endomysial connective tissue and fatty infiltration Fiber degeneration Fiber regeneration Dystrophin: reduced (usually 10%-60% of normal)
Blood chemistry and hematology	CK: Very high (10,000-50,000) High AST and ALT (normal GGT) High aldolase	CK: 5,000-20,000 Lower levels with increasing age

ANTERIOR HORN DISORDERS IN CHILDREN

Spinal Muscular Atrophy

The SMAs comprise a group of autosomal recessive disorders characterized by progressive weakness of the lower motor neurons.

SMA type I (acute infantile or Werdnig-Hoffmann): Onset is from birth to 6 months.

SMA type II (chronic infantile): Onset is between 6 and 18 months.

SMA type III (chronic juvenile): Onset is after 18 months.

SMA type IV (adult onset): Onset is in adulthood (mean onset, mid-thirties).

SMA TYPE I – ACUTE INFANTILE OR WERDNIG-HOFFMANN DISEASE

Presents before 6 months of age – 95% of patients have signs and symptoms by 3 months. Severe, progressive muscle weakness and flaccid or reduced muscle tone.
Reports of impaired fetal movements are frequently observed.
Prolonged cyanosis may be noted at delivery.

Clinical signs: