Page 355 - Motor Disorders Third Edition
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of life and sometimes at birth. Neither plasma exchange nor THE HYPOTONIC INFANT / 337
immune suppression offer a demonstrable benefit, but some hypertrophic cardiomyopathy. Electromyography shows
patients may respond favorably to cholinesterase inhibitors, evidence of a generalized myopathy with occasional posi-
quinidine, or 3, 4-diaminopyridine. tive sharp wave activity, fibrillation potentials, bizarre repeti-
tive discharges, and myotonic discharges in the absence of
Primary muscle disease is an important cause of infan- clinically detectable myotonia (43, 44). Muscle biopsy shows
tile hypotonia. The congenital myopathies are clinically and vacuolar myopathy that stains positively with the periodic
morphologically distinctive on skeletal muscle biopsy. They acid-Schiff technique. Diastase digestion of fresh frozen tis-
include multicore and central core disease, nemaline myop- sue sections removes most vacuolar material, consistent with
athy, myotubular or centronuclear myopathy, and congeni- the presence of glycogen. EM shows glycogen sequestered
tal fiber type disproportion of small type I and large type into membrane-bound autophagic vacuoles (43, 44). Other
II myofibers (37) each of which presents with true muscle metabolic myopathies that present with infantile hypotonia
weakness, feeding difficulty, decreased tendon reflexes, and include the mitochondrial DNA depletion syndrome, cyto-
respiratory failure, often in association with mental retarda- chrome c oxidase (COX) deficiency, glycogenosis type IV or
tion, dysmorphic physical features, scoliosis, and congeni- debrancher enzyme deficiency, and glycogenosis type V or
tal hip dislocation. myophosphorylase deficiency. Lactic acidosis is a frequent
associated finding in mitochondrial DNA depletion syn-
By comparison, CMD shows primary myopathic changes drome and COX deficiency.
in a skeletal muscle biopsy without distinctive histochemical
or ultrastructural features. Infants with CMD are symptom- The possibility of an exogenous toxin should be consid-
atic from birth or the first few months of life. They manifest ered in cases of acute and recurrent hypotonia. Although
hypotonia, delayed motor milestones, early and severe con- routine urine toxicology screens commonly detect drugs,
tractures, and joint deformity. Serum creatine kinase (CK) one should remain alert to the continued possibility of a
is up to 30 times normal in early disease stages and then toxic substance when the initial screen is reported to be nega-
decreases rapidly. The Fukuyama form of CMD caused by tive. In a report of Munchausen syndrome, chronic ipecac
mutations in the gene encoding fukutin is characterized by or emetine poisoning in infancy resulted in hypotonia, poor
severe mental retardation in all cases and seizures in about suck, and respiratory insufficiency (45). Carbamate and
half. MRI reveals cerebral and cerebellar polymicrogyria organophosphate poisoning results in meiosis, flaccid mus-
reflecting a neuronal migration defect. Although affected cle tone; fasciculation; dyspnea; and stupor. Atropine sulfate
children never walk, they may live into adulthood (38, 39). in doses of 0.05 mg/kg repeated at regular intervals dra-
An occidental type of CMD occurs in infants from Western matically improves cholinergic crisis symptoms, including a
countries with clinical skeletal muscle involvement alone. A depressed level of consciousness (46). Ingestion of ethylene
subset of both types has a specific absence of merosin, the glycol produces vomiting, irritability, acidosis, and hypoto-
?2 chain of laminin-2, by immunocytochemistry and immu- nia suggestive of a metabolic disorder. Organic acid analysis
noblot (40, 41). Fukuyama CMD shares a common disease reveals glycolic acid and a positive anion gap, and urinalysis
mechanism of hypoglycosylation of ?-dystroglycan with shows hematuria and calcium oxalate crystals (47).
two other CMD, Walker-Warburg syndrome and muscle-
eye-brain disease. The latter disorders due to mutations in Finally, after excluding all other etiologies, a benign condi-
the POMT1 and POMGnT genes, respectively; further simi- tion may be the cause of infant hypotonia. Essential hypoto-
larities include neuronal migration defects and ocular abnor- nia is applied to otherwise healthy infants with unexplained
malities (42). hypotonia, normal strength and tendon reflexes, and normal
physical characteristics. The presence of an older sibling with
Metabolic myopathies frequently cause myotonia and infantile hypotonia as an isolated finding and normal tone
weakness. Pompe disease or glycogen storage disease (GSD) later in childhood is supportive.
type II, is an AR metabolic myopathy due to deficiency of
the enzyme acid maltase. Affected infants are normal at birth ACKNOWLEDGMENT
but soon develop generalized hypotonia, weakness, macro-
glossia, and hepatomegaly. Electrocardiogram abnormalities Funding was provided by The Colleen Giblin Foundation.
include giant QRS complexes, short PR interval, and ven-
tricular hypertrophy. Echocardiography reveals concentric
