Hypotonia in Infants

Hypotonia is reduced resistance to passive movement of joints. The deficits causing hypotonia can originate in the brain, spinal cord, peripheral nerves, neuromuscular junction, and muscle. There are also non-neuromuscular entities that may be associated with hypotonia including:

  1. Prematurity
  2. Hypothyroidism
  3. Rickets
  4. Malnutrition
  5. Kernicterus
  6. Storage diseases
  7. Down Syndrome
  8. Sepsis
  9. Congestive Heart failure
  10. Hypoglycemia

The differential diagnosis of hypotonia is organized anatomically into central and peripheral causes. Peripheral hypotonia is further divided into disorders of anterior horn cells, peripheral nerves, neuromuscular junction, and muscle. In general, a good history, physical examination, and neurologic exam will lead to the diagnosis.

Characteristics of central hypotonia (60-80% of cases)

History:

  • Seizures
  • Delay in attaining normal milestones

Physical Exam:

  • Unable to track objects visually
  • Fail to imitate facial gestures
  • Lethargic 
  • Hyperactive DTRs, clonus, persistence of primitive reflexes
  • Poor head control

Characteristics of Peripheral Hypotonia (15-30% of cases)

History:

  • Normal sleep-wake patterns
  • Feeding difficulties

Physical Exam:

  • Responds appropriately to surroundings
  • Profound generalized weakness
  • Absent reflexes

Causes of Central Hypotonia

Hypoxic encephalopathy (19% of cases)
Intracranial hemorrhage
Perinatal trauma
Infections – meningitis or encephalitis
Structural abnormalities
Chromosomal and Genetic abnormalities (31%)

Trisomy 21 (Down Syndrome)

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http://gizmodo.com/scientists-may-have-found-a-genomic-off-switch-for-do...
 

  • Characteristic features: hypotonia, mental retardation, and congenital heart defects
  • Dysmorphic features present in neonates: flat facial profile and nasal bridge, short neck with excess uncial folds, single transverse palmer crease, upslanting palpebral fissures

Fragile X

fragilex.jpg
http://medgen.genetics.utah.edu/photographs/pages/fragile_x.htm

  • Genetic defect: expansion of trinucleotide repeat (CGG) on X chromosome
  • Hypotonia is mild and kids are usually diagnosed after failure to meet developmental milestones
  • Characteristic features: mental retardation, autistic features, macrocephaly, large ears, increased testicular size in puberty

Prader-Willi syndrome:

  • Characteristic features: hypotonia, hypogonadism, mental retardation, short stature, and obesity
  • Genetic defect: deletion of paternal copy of long arm of chromosome 15q11-13 or maternal uniparental disomy

Causes of Peripheral Hypotonia

Cervical Cord Trauma

  • Secondary to difficult delivery, usually breech or cervical presentation
  • Initially present with hyporeflexia and later develop hyperreflexia and spasticity after days to weeks
  • Development of neurologic deficits below the cervical area including: respiratory depression, vasomotor instability, bladder dysfunction, decreased rectal tone

Anterior Horn Cell Disorders

Werdig-Hoffman syndrome (Spinal Muscle Atrophy)

  • degeneration of anterior horn cells
  • Autosomal recessive
  • 1/3 present in the neonatal period
  • Maternal history: decreased fetal movements and breech presentation
  • Features: hypotonia, weakness, absent reflexes, tongue and muscle fasciculations
  • Infants are very alert and develop normal intelligence

Pompe Disease

pompe_0.jpg
https://en.wikipedia.org/wiki/Glycogen_storage_disease_type_II

  • Glycogen storage disease type II: acid maltase deficiency
  • Glycogen deposits in the anterior horn cells, liver, brain and heart
  • Associated with cardiomyopathy and hepatosplenomegaly
  • Diagnosis is made by muscle biopsy showing vacuolar myopathy (see image)

Poliomyelitis

  • Destruction of anterior horn cells by polio virus
  • Features: abrupt onset of asymmetric weakness, bulbar involvement and encephalitis may be present
  • Can recover virus from stool 

NMJ-Related Disorders

Transient myasthenia gravis (MG)

  • 10% of neonates with mothers who have MG
  • Mother’s antibodies against acetycholine receptor cross the placenta and effect the newborn
  • Features: decreased tone, weakness, poor suck, and decreased movements. May be confused with sepsis.
  • Diagnosis confirmed by temporary reversal of symptoms upon edrophonium or neostigmine challenge
  • Mean duration of symptoms 18 days, typically resolves in 6 weeks

Congenital myasthenia gravis (MG)

  • Presents in early infancy with ptosis and ophthalmoplegia (features uncommon in transient MG)
  • Severe respiratory symptoms requiring assisted ventilation at birth
  • Persistent episodes of apnea and weakness

Infantile botulism

  • Infant ingests C. botulinum spores that germinate in the GI tract and release an serotoxin that interferes with the release of acetycholine.
  • Subacute or acute onset of hypotonia
  • 4-5 day prodrome of constipation, poor feeding, lethargy prior to development of ptosis, decreased eye movements, weakness and areflexia.
  • Progressive muscle weakness can lead to respiratory failure requiring ventilatory support.
  • Usually self limited, lasting 2-6 weeks
  • Treatment: IV human botulism IG

Aminoglycosides - interfere with the presynaptic release of acetylcholine

 Hypermagnesemia

  • Occurring secondary to treatment of eclampsia with magnesium sulfate
  • Mg2+ inhibits release of acetylcholine
  • Leads to weakness, hypotonia, and increased risk of respiratory failure

Congenital Myopathies

  • There are many forms of myopathies that present in the neonatal period.
  • Typical features: hypotonia, hyporeflexic, facial paralysis, high arched palate
  • Diagnosis: muscle biopsy

Congenital Myotonic Dystrophy (Steinert disease)

  • Infants born to mothers with moronic dystrophy
  • Maternal history: polyhydramnios, prolonged labor, and uterine dystocia
  • Symptoms at birth: hypotonia, facial weakness, areflexia, and respiratory distress
  • Characteristic facial features: tenting of upper lip, thin cheeks, wasting of temporalis muscle
  • Motor function improves after 3rd weeks, if infant survives

Benign Congenital Hypotonia

  • Diagnosis of exclusion
  • Hypotonia, but no weakness
  • The reflexes are normal or hypoactive
  • There may be a slight delay in motor milestones, otherwise development is normal
  • IQ usually normal
  • Complications: joint hypermobility leading to frequent joint dislocations especially the shoulder

References

  1. Steifel L. Hypotonia in Infants. Pediatrics in Review. March 1996
  2. Arnon S. et al. Human Botulinism Immune Globulin for the Treatment of Infant Botulism. NEJM Feb 2. 2006.
  3. NEJM Case: A Newborn Boy with Hypotonia.  NEJM Nov. 16 2006
  4. Francisco A.M. and Arnon S. Clinical Mimics of Infant Botulinism.  Pediatrics April 2007
  5. Long S. Infant Botulism and Treatment with BIG-IV.  Pediatric Infectious Disease Journal March 2007
  6. Harris, Susan R. Congenital hypotonia: clinical and developmental assessment. Developemental Medicine & Child Neurology May 2008
  7. Peredo D, Hannibal M.  The Floppy Infant.  Pediatrics in Review September 2009

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