Hypotonia in infants

Hypotonia is decreased muscle tone characterized by reduced resistance to passive movement that is often described by caregivers as "floppiness" in infants. It is classified as central when the underlying disorder affects the central nervous system (CNS) and peripheral when it affects the peripheral nervous system (PNS), although some conditions have mixed central and peripheral features. CNS causes include genetic syndromes (e.g., Down syndrome, Prader-Willi syndrome) and brain injury, while PNS causes include spinal muscular atrophy and infant botulism. The clinical evaluation begins with a detailed history and complete neurological examination to differentiate hypotonia from weakness and classify the hypotonia as central and/or peripheral. Initial diagnostic studies aim to identify immediately treatable systemic conditions (e.g., pediatric sepsis, hypoglycemia). Additional specialist-directed diagnostics (e.g., neuroimaging, genetic testing) are based on clinical presentation and the suspected underlying cause. Acute management focuses on stabilization and treating any life-threatening secondary causes. Long-term management involves treating the primary underlying cause and providing multidisciplinary supportive care for hypotonia.

Hypotonia in infants is classified as central if the cause is a disorder affecting the CNS or peripheral if the cause is a disorder affecting the PNS.

Central nervous system ^[1]

Brain

• Genetic syndromes, e.g. : ^[4][5]
  • Prader-Willi syndrome and Angelman syndrome
  • Down syndrome
  • Noonan syndrome
  • 22q11.2 deletion syndrome
  • Neurofibromatosis type 1
• Structural brain malformations ^[2]
  • Lissencephaly
  • Holoprosencephaly ^[6]
  • Chiari malformation
• Infections
  • Neonatal meningitis
  • Congenital TORCH infections
• Acquired brain injury
  • Hypoxic-ischemic encephalopathy
  • Intracranial hemorrhage
• Inborn errors of metabolism, e.g.:
  • Urea cycle disorders
  • Organic acidemias
  • Lysosomal storage diseases
  • Peroxisomal disorders
• Fetal drug exposure: alcohol, benzodiazepines, opioids, antidepressants

Spinal cord

• Spinal cord injury (e.g., due to birth trauma) ^[2]
• Spina bifida
• Syringomyelia
• Arteriovenous malformation

Systemic conditions

• Neonatal bacterial sepsis and pediatric sepsis
• Congenital heart disease 37847
• Neonatal hypoglycemia
• Congenital hypothyroidism

Peripheral nervous system ^[1][2]

Motor neuron

• Spinal muscular atrophy (type 0 SMA and type 1 SMA)
• Poliomyelitis

Peripheral nerve

• Hereditary motor sensory neuropathy
• Hereditary sensory and autonomic neuropathy type III
• Spinal muscular atrophy with respiratory distress type 1
• Guillain-Barré syndrome (rare in infants)

Neuromuscular junction

• Congenital myasthenic syndromes
• Transient neonatal myasthenia gravis
• Infant botulism
• Aminoglycoside toxicity

Muscle and connective tissue

• Progressive muscular dystrophies, e.g.:
  • Duchenne muscular dystrophy
  • Congenital muscular dystrophy
• Congenital myopathies (e.g., central core disease, nemaline myopathy)
• Congenital myotonic dystrophy
• Infantile-onset type 2 glycogen storage disease
• Mitochondrial myopathies
• Carnitine transporter deficiency
• Ehlers-Danlos syndrome and Marfan syndrome

Approach ^[7][8]

• Identify red flags in infantile hypotonia.
  • Initiate acute stabilization measures in the ICU as indicated, e.g.: ^[7]
    • Airway management in children
    • Pediatric respiratory support
    • Continuous cardiac monitoring and pulse oximetry
    • Hemodynamic support
    • Acute seizure management
  • Immediately consult a specialist (e.g., pediatric neurologist, critical care).
• Review newborn screening results, if available. ^[5]
• Perform initial diagnostics to identify treatable conditions (e.g., neonatal bacterial sepsis, neonatal hypoglycemia).
• Obtain additional diagnostic testing based on the suspected underlying etiology.

Red flags in infantile hypotonia ^[8]

Any of the following requires immediate intervention and/or immediate pediatric neurology consultation.

• Clinical features of respiratory distress in children
• Signs of serious infection, e.g.:
  • Clinical features of sepsis in children
  • Clinical features of neonatal bacterial infection
• Signs of bulbar dysfunction
• Seizures or altered mental status
• Severely elevated (e.g., serum creatine kinase > 50,000 U/L) ^[8]

Focused history ^[1][5]

• Prenatal and birth history
  • Birthing parent medical conditions and medication use
  • Pregnancy and/or delivery complications
• Infant history
  • Onset and progression of hypotonia
  • Signs and symptoms suggesting a CNS disorder, e.g.:
    • Reduced alertness
    • Feeding issues
    • Respiratory problems
    • Seizures
  • Developmental milestones
• Family history ^[5]
  • Neurological conditions and neuromuscular disease
  • Genetic disorders
  • Pregnancy loss
  • Motor or other developmental delay
  • Consanguinity

Physical examination

Focused general examination ^[1][5]

• Signs of pediatric respiratory distress
• Pediatric vital signs
• Pediatric growth assessment
• Features of an underlying cause, e.g.:
  • Facial features characteristic of genetic disorders
  • Chest and limb abnormalities (e.g., contractures, deformities)
  • Skin dimpling of the knees and/or elbows ^[1][2]
  • Organomegaly

Infants with neuromuscular weakness may develop respiratory failure without obvious preceding symptoms (e.g., dyspnea). ^[9]

Complete neurological examination ^[1][5]

• Alertness
• Cranial nerve assessment
  • Facial weakness and ptosis
  • Extraocular movements
  • Tongue fasciculations
• Muscle bulk
• Evaluation of muscle tone and strength (both active and passive) including:
  • Spontaneous antigravity movements
  • Resting posture (supine and/or sitting position) ^[1]
  • Maneuvers to assess postural tone and strength
    • Axial suspension: assesses shoulder girdle tone
    • Ventral suspension: assesses tone of the trunk, neck, and extremities
    • Traction response: assesses for head lag
    • Scarf sign: assesses shoulder girdle tone
• Reflexes
  • Deep tendon reflexes
  • Primitive reflexes

The absence of antigravity movement is strongly suggestive of a peripheral cause of hypotonia in infants. ^[7]

Muscle tone and muscle strength are not synonymous and must be evaluated individually. ^[1]

Initial laboratory studies for hypotonia in infants ^[1][7]

• CBC
• CMP
• Thyroid function tests
• Creatine kinase ^[1][5]
• Serum ammonia and lactate
• ABG
• Troponin, CK-MB
• Suspected sepsis ^[1]
  • Neonates: diagnostics for neonatal bacterial sepsis
  • Older infants: initial studies for sepsis in children

Review newborn screening results in all patients with hypotonia, as they may reveal potential causes of hypotonia (e.g., inborn errors of metabolism, spinal muscular atrophy). ^[1][5]

Additional studies ^[1][5]

Obtain additional studies in consultation with a specialist, based on clinical presentation and the suspected underlying cause.

• Imaging
  • Central hypotonia: neuroimaging (cranial ultrasound, brain MRI, and/or spine MRI)
  • Suspected heart disease: echocardiogram and chest x-ray
  • Organomegaly: abdominal imaging
  • Suspected fractures: skeletal survey
• ECG: suspected underlying genetic syndrome
• EEG: patients with seizures and/or encephalopathy
• CSF analysis: for suspected CNS infection or metabolic disorder ^[1]
• Biochemical testing: for suspected inborn errors of metabolism ^[3]
• Genetic testing
  • For suspected genetic causes of central or peripheral hypotonia
  • Modalities include microarray, karyotype, targeted gene testing, and whole genome sequencing.
• Muscle and/or nerve studies ^[1][7]
  • Typically reserved for diagnostic uncertainty after genetic testing in peripheral hypotonia
  • Modalities include electrodiagnostic studies and muscle and/or nerve biopsy.
• Referrals for ophthalmologic examination and diagnostics for hearing loss in children to evaluate for associated abnormalities. ^[1]

In peripheral hypotonia, genetic testing is typically performed before more invasive testing, such as electrodiagnostic studies and biopsy. ^[1][2][7]

In addition to disease-specific therapies, children may require long-term management of symptoms and associated conditions, including: ^[2][9]

• Respiratory support in children (e.g., spirometry, airway clearance, noninvasive ventilation) ^[21]
• Nutritional support (e.g., gastrostomy tube placement)
• Physical and occupational therapy for motor and functional impairments
• Speech therapy and/or chestfeeding support for sucking, swallowing, and speech difficulties ^[5]
• See also "Management of abnormal pediatric development." ^[5]