The Hypotonic Infant & Pediatric Neuromuscular Disease

Localizing the floppy infant

Tone versus strength. Hypotonia is reduced resistance to passive movement; weakness is reduced power. Most floppy infants have a central cause, with low tone but relatively preserved strength. Motor unit (peripheral) disease makes an infant floppy and weak, unable to lift the limbs against gravity.

Central clues. Prader-Willi syndrome (loss of paternally expressed genes at 15q11–q13) causes severe neonatal hypotonia, poor suck, and genital hypoplasia, followed later by hyperphagia and obesity; DNA methylation analysis is the best first test because it detects paternal deletion, maternal uniparental disomy, and imprinting defects. Sepsis and metabolic disease also produce central hypotonia.

Spinal muscular atrophy

Genetics. Autosomal recessive homozygous deletion of SMN1 (chromosome 5q) causes degeneration of anterior horn cells. The backup gene SMN2 makes mostly truncated protein because exon 7 is skipped; more SMN2 copies mean milder disease.

Type 1. Onset before 6 months; the infant never sits. Findings: profound symmetric proximal weakness, areflexia, tongue fasciculations, frog-leg posture, weak cry and suck, and a bell-shaped chest with paradoxical abdominal breathing, because intercostals fail while the diaphragm is spared. The face is alert and sensation is normal. Untreated, most die of respiratory failure in early childhood. In type 2 children sit but never walk; in type 3 they walk and later lose the ability.

Diagnosis and treatment. SMA is on the US newborn screening panel; SMN1 deletion testing confirms it. Treatment works best before symptoms:

• Nusinersen — intrathecal antisense oligonucleotide that makes SMN2 include exon 7
• Onasemnogene abeparvovec — one-time IV AAV9 gene therapy delivering SMN1, for children younger than 2 years
• Risdiplam — oral SMN2 splicing modifier

Supportive care includes noninvasive ventilation, cough assistance, gastrostomy feeding, and scoliosis management.

Infant botulism

Pathogenesis. Infants younger than 12 months (most under 6 months) swallow Clostridium botulinum spores from soil, construction dust, or honey. Immature gut flora lets the spores germinate and make toxin in situ; the toxin cleaves SNARE proteins and blocks presynaptic acetylcholine release. Most cases involve no honey, but honey is still avoided before 12 months.

Presentation. Constipation often comes first, then poor suck, weak cry, drooling, ptosis, sluggish pupils, and facial weakness, followed by symmetric descending flaccid paralysis that can reach the respiratory muscles. The infant is afebrile and alert.

Management. Give human-derived botulism immune globulin (BabyBIG) on clinical suspicion; it shortens ventilation and hospital stay. Stool toxin testing confirms the diagnosis days later. Support the airway and feeding.

Avoid aminoglycosides, which worsen neuromuscular blockade and can precipitate respiratory failure; antibiotics are not part of treatment.

Duchenne and Becker muscular dystrophy

Duchenne. X-linked frameshift deletions in the dystrophin gene (Xp21) leave no dystrophin. Boys present at 2–5 years with clumsiness, falls, waddling gait, toe walking, Gowers sign (climbing up the thighs to stand), and calf pseudohypertrophy from fibrofatty replacement. CK is 10–100 times normal, and AST/ALT are elevated from muscle, not liver. DMD deletion/duplication testing confirms the diagnosis; muscle biopsy is reserved for nondiagnostic genetics.

Management. Daily glucocorticoids (prednisone or deflazacort) prolong walking and delay scoliosis and respiratory decline; untreated boys stop walking around age 12. Screen for dilated cardiomyopathy with echocardiography or cardiac MRI and start an ACE inhibitor early; follow pulmonary function and add cough assistance and noninvasive ventilation. Death usually results from respiratory or cardiac failure. Female carriers can develop cardiomyopathy.

Avoid succinylcholine and volatile anesthetics in dystrophinopathies: they can trigger hyperkalemic cardiac arrest and rhabdomyolysis.

Maternal clues and Guillain-Barré syndrome

Congenital myotonic dystrophy. Myotonic dystrophy type 1 is an autosomal dominant CTG repeat expansion in DMPK that enlarges across generations (anticipation); the congenital form comes almost always from an affected mother. Polyhydramnios and reduced fetal movement precede severe hypotonia, facial diplegia with a tented upper lip, poor feeding, respiratory failure, and clubfeet. Examine the mother for grip myotonia and facial weakness.

Transient neonatal myasthenia. Maternal anti-acetylcholine receptor IgG crosses the placenta and affects about 10–20% of infants of mothers with myasthenia gravis, independent of maternal severity. Weak suck and cry, feeding difficulty, hypotonia, and occasionally respiratory weakness appear within 3 days. Care is supportive, with pyridostigmine if needed; weakness resolves over weeks as antibodies clear.

Guillain-Barré syndrome. An acute demyelinating polyradiculoneuropathy 1–3 weeks after a respiratory or GI infection (for example Campylobacter). Children often present with leg pain and refusal to walk, then ascending symmetric weakness with areflexia, sometimes with facial weakness and autonomic instability. CSF shows albuminocytologic dissociation. Monitor breathing closely and give IVIG or plasma exchange for significant or progressive weakness; corticosteroids do not help.

Ascending paralysis with a normal CSF: search the scalp for an engorged tick, because removal cures tick paralysis.