Congenital myopathies (CM) are a relatively common group (prevalence approximately 1:20,000) of nondystrophic muscle disorders that, like congenital muscular dystrophies, most typically present in infancy with hypotonia and weakness. Additional signs and symptoms include congenital contractures, hip subluxation/dislocation, small/atrophic muscles, thin body habitus, and characteristic facial appearance (the “myopathic facies”). Symptoms are often nonprogressive or only slowly progressive, although children often have severe lifelong disabilities including wheelchair dependence, severe scoliosis, and respiratory failure. Clinical finding may distinguish CMDs and other dystrophies (e.g., involvement of the facial musculature in congenital myopathies). Diagnosis is ultimately established based on laboratory studies, biopsy findings, and genetic test results. Histopathologic subtypes are distinguished by characteristic features on muscle biopsy, the most common being nemaline myopathy, centronuclear myopathy, and core myopathy. More than 15 different genetic causes have been established for CMs. However, nearly 50% of cases are genetically unresolved. Although no specific therapies currently exist for any CM subtype, several promising therapies have shown efficacy in preclinical models of disease.
Glycogen storage disease type II (Pompe disease) and musclecarnitine deficiency are discussed in Chapters 52 and 55. Several mitochondrial myopathies may present with hypotonia, ophthalmoplegia, and progressive weakness, but the phenotype ofthese disorders is broad (Chapter 57). Endocrine myopathies, including hyperthyroidism, hypothyroidism, hyperparathyroidism, and Cushing syndrome, are associated with proximalmuscle weakness. Periodic paralysis due to familial forms of hypokalemia or hyperkalemia produces episodic weakness.
The diagnostic evaluation should be guided by the clinical history and physical examination (Chapter 179).
Malignant hyperthermia is a life-threatening syndrome manifested by a rapid increase of body temperature, muscle rigidity, metabolic and respiratory acidosis, hypotension, arrhythmias, and convulsions. Acute episodes are precipitated by exposure to anesthetic agents in patients with a genetic predisposition. Patients with Duchenne muscular dystrophy, central core myopathy, and other myopathies are susceptible, although malignant hyperpyrexia can also occur in children without muscle disease as an autosomal dominant genetic disorder. A family history of unexplained death during anesthesia is often noted. Serum CK levels rise and myoglobinuria can result in tubular necrosis and acute renal failure. Diagnosis of idiopathic malignant hyperthermia is possible with genetic testing or an in vitro muscle contraction test that reveals excessive tonic contracture on exposure to halothane and caffeine. Treatment consists of IV dantrolene, sodium bicarbonate, and cooling.
The clinical distinction between upper and lower motor neuron disorders in infants is blurred because incomplete myelinization of the developing nervous system limits expression of many of the cardinal signs, such as spasticity. The two critical clinical points are whether the child is weak and the presence or absence of deep tendon reflexes. Hypotonia and weakness coupled with depressed or absent deep tendon reflexes suggest a neuromuscular disorder. A stronger child with brisk reflexes suggests an upper motor neuron source for the hypotonia. Causes of neonatal weakness are outlined earlier. A diagnostic algorithm for infants with hypotonia or weakness is presented in Figure 182-1.
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Some infants who appear to move well when supine in theircribs are floppy when handled or moved. When lifted, their
Dysmorphic?
CK, cDM1, SMA Brain MRI
S MRI CK, PWS
No Diagnosis?