A newborn or young infant with reduced postural tone. Classic findings: head lag on traction, "frog-leg" posture at rest, slipping through the examiner's hands on vertical suspension, a U-shape on ventral suspension. "Floppy" is a chief-complaint word; the work is in localizing where the floppiness comes from.
This is the single most useful bedside distinction and shapes the entire work-up.
| Feature | Central (brain) | Peripheral (motor unit) |
|---|---|---|
| Mental status | Often depressed, less interactive | Alert, engaged, frustrated |
| Reflexes | Preserved or brisk | Reduced or absent |
| Antigravity strength | Weakness less prominent than tone | Profound; can't lift limb against gravity |
| Fasciculations | Absent | May be present (especially tongue in SMA) |
| Cry / suck | Usually normal | Weak |
| Respiratory effort | Usually adequate | Diaphragmatic, paradoxical, fatigues |
| Dysmorphic features | Common (syndromic) | Usually absent |
Rule of thumb: central hypotonia outnumbers peripheral roughly 2:1. But peripheral causes are more often urgent and more often have disease-modifying therapy now, so don't anchor.
The brain is "running the body softly." Look for dysmorphism, anomalies, encephalopathy, seizures.
- Down syndrome: most common chromosomal cause of neonatal hypotonia; usually obvious on exam.
- Prader-Willi syndrome: severe neonatal hypotonia plus poor feeding that later evolves into hyperphagia; almond eyes, narrow bifrontal diameter. Methylation testing is the single best first-line test.
- Hypoxic-ischemic encephalopathy: perinatal event, low Apgars, multisystem injury.
- Congenital infections (TORCH): microcephaly, intracranial calcifications, organomegaly.
- Zellweger spectrum: high forehead, large fontanelle, hepatomegaly plus seizures plus profound hypotonia. VLCFAs are the first-line test.
- Mitochondrial disease (Leigh, others): lactic acidosis, multisystem.
The brain is fine; the lesion is below it. Anatomy from proximal to distal:
Anterior horn cell
- Spinal muscular atrophy (SMA): the must-not-miss diagnosis. Symmetric proximal weakness, tongue fasciculations, areflexia, preserved facial movement. Newborn screening covers it in most US states. Disease-modifying therapies (nusinersen, onasemnogene abeparvovec, risdiplam) work best when started early. Send SMN1 deletion testing today.
Peripheral nerve
- Rare presenting cause in true neonatal hypotonia. Charcot-Marie-Tooth (CMT) generally presents later.
Neuromuscular junction
- Congenital myasthenic syndromes: fluctuating weakness, fatigability, ptosis. Distinguish from transient neonatal myasthenia (mother has MG; resolves).
Muscle
- Pompe disease (GSD type II): hypertrophic cardiomyopathy plus profound weakness. Acid α-glucosidase activity is the diagnostic test; treatable with ERT, so don't miss it.
- Myotonic dystrophy type 1, congenital form: almost always inherited from the mother (anticipation). Tented upper lip, polyhydramnios history, severe weakness, talipes. Check mom for grip myotonia.
- Congenital muscular dystrophies (α-dystroglycanopathies, LAMA2): early weakness with elevated CK; some have brain and eye involvement.
- Mitochondrial myopathies: lactic acidosis with weakness.
- Nemaline / congenital myopathies: biopsy-defined.
- Respiratory distress, weak cry, paradoxical breathing → SMA or congenital muscular dystrophy until proven otherwise. Don't wait for the genetics; admit and monitor.
- Hypertrophic cardiomyopathy + hypotonia → Pompe disease. ERT is most effective if started before 6 months.
- Tongue fasciculations → SMA.
- Massive hepatomegaly + neonatal seizures + dysmorphism → peroxisomal (Zellweger) or LSD.
- Maternal grip myotonia → congenital myotonic dystrophy in the infant.
The right first test depends on the localization step above. A reasonable opening battery for an undifferentiated floppy infant:
- CK: elevated in muscle disease (Pompe, congenital MD), normal in anterior horn cell and central causes.
- SMA deletion testing (or trust the newborn screen if already done). Turnaround is fast, and a positive result changes management immediately.
- Karyotype + chromosomal microarray: Down syndrome, microdeletion syndromes.
- Methylation analysis at 15q11-q13 if Prader-Willi is on the table.
- VLCFAs if a peroxisomal disorder is suspected.
- Lactate, ammonia, acylcarnitines, urine organic acids for metabolic causes.
- MRI brain for central etiologies, especially with seizures or focal findings.
Exome / genome sequencing has overtaken the older tiered approach in most centers when the first-pass tests are unrevealing. Discuss timing with neurology and genetics.
- Always examine the mother. Congenital myotonic dystrophy is the classic "you have to examine mom" diagnosis. Her grip myotonia clinches it before any genetic test runs.
- Central hypotonia + normal CK is the most common combination by far, but the rare peripheral cases are the ones that earn you grudging respect later.
- "Frog-leg posture with full alertness" is the SMA setup question on every exam.