Chang-Yong Tsao, MD, FAAN, FAAP

DESCRIPTION

The term hypotonic infant refers to an infant with hypotonia or decreased muscle tone. Muscle tone is controlled by afferent muscle spindles and α- and γ-motor neurons in the spinal cord and also is affected by upper motor neurons and corticospinal tract. Hypotonia is characterized by diminished resistance to passive movements and an excessive range of joint mobility. Hypotonic infant syndrome may be seen not only with severe muscle weakness, but also with only mild weakness or even without obvious weakness.

EPIDEMIOLOGY

Incidence

Hypotonic infant syndrome is commonly seen in the clinical practice; however, its incidence or prevalence is not known because it is seen with a large variety of diseases.

Prevalence

Same as above.

RISK FACTORS

Occurs more often in the newborn period and the first year of life.

Genetics

Varies depending on the underlying conditions.

GENERAL PREVENTION

Vaccinations can prevent illness and worsening of hypotonia.

PATHOPHYSIOLOGY

Varies depending on the underlying conditions.

ETIOLOGY

Lesions at any level of the nervous system, including upper and lower motor units, can cause hypotonia. Hypotonia combined with severe muscle weakness usually is associated with lower motor neuron disorders, including diseases affecting anterior horn cells of the spinal cord, peripheral nerves, neuromuscular junctions, and muscles. Hypotonia without obvious weakness often points to diseases of the CNS, connective tissue disorders, and chromosomal diseases or those involving metabolic, endocrine, or nutritional problems.

COMMONLY ASSOCIATED CONDITIONS

Medically treatable hypotonia refers to a condition that can be cured with specific medical treatment. Hypothyroidism due to thyroid hormone deficiency may present with hypotonia, constipation, failure to thrive, developmental delay, jaundice, and retardation of bone growth. Biotinidase deficiency may present with hypotonia, seizures, ataxia, alopecia, skin rash, developmental delay, sensorineural deafness, and lactic acidosis. Neonatal myasthenia gravis may present with hypotonia, severe generalized weakness, and respiratory failure. Infantile botulism due to Clostridium botulinum toxins occurs in previously healthy infants in the first few months of life, with sudden generalized weakness, hypotonia, poor sucking and swallowing, constipation, ptosis, dilated pupils with sluggish light reflex, lethargy, and respiratory distress. Infantile Guillain–Barré syndrome is characterized by progressive generalized weakness and areflexia, hypotonia, and respiratory failure. Tick paralysis is caused by the persistent tick bite with secretion of its toxin, leading to sudden generalized weakness and areflexia and hypotonia in a formerly normal child.

[Outline]

• Information
• Description
• Epidemiology
  • Incidence
  • Prevalence
• Risk Factors
  • Genetics
• General Prevention
• Pathophysiology
• Etiology
• Commonly Associated Conditions

HISTORY

Hypotonic infants may present with severe weakness, mild weakness, or no weakness; may have dysmorphic features, seizures, speech or language delay, or other organ abnormalities.

PHYSICAL EXAM

• Hypotonia is characterized by diminished resistance to passive movements and an excessive range of joint mobility.
• Hypotonia with significantly severe muscle weakness and atrophy, decreased or absent deep tendon reflexes, and fasciculation, but without Babinski's sign or clonus, frequently suggests lower motor unit diseases involving anterior horn cells, peripheral nerves, neuromuscular junction, or muscles.
• Hypotonia with little or no weakness, normal or increased deep tendon reflexes, craniofacial dysmorphic features, Babinski's sign, ankle or knee clonus, or other brain dysfunctions such as language delay, mental retardation, progressive intellectual decline, seizures, aggressive behavior problems, or attention deficit hyperactivity often indicates upper motor unit diseases that affect the cerebrum, cerebellum, brainstem, or spinal cord above anterior horn cells.
• However, there are diseases with both upper and lower motor unit involvements, such as mitochondrial encephalomyopathy, congenital myotonic dystrophy, and metachromatic leukodystrophy.

DIAGNOSTIC TESTS AND INTERPRETATION

Lab

Initial Lab Tests

• For lower motor unit diseases
  • Serum creatine kinase may be increased in a variety of muscle disorders and some spinal muscular atrophy and should be done before electromyography and nerve conduction studies.
• For upper motor unit diseases
  • Serum studies: Very long chain fatty acids for neonatal adrenoleukodystrophy; amino and organic acids, lactate, pyruvate, ammonia, carnitine for disorders of amino acids, organic acids, lactic acids, and urea cycle; lysosomal enzymes for lysosomal disorders; thyroid hormones for hypothyroidism; antibody titers for intrauterine infections (toxoplasmosis, rubella, cytomegalovirus, herpes), blood and urine guanidinoacetate, creatine, and creatinine for inborn errors of creatine metabolism.

Follow-Up & Special Considerations

• Blood DNA tests may detect survival motor neuron gene 1 homozygous deletions for spinal muscular atrophy, abnormal CTG trinucleotide repeat expansion for congenital myotonic dystrophy, and mitochondrial DNA mutations of some mitochondrial encephalomyopathies such as mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (1)[A].
• Other: Stool for culture and exotoxin detection of C. botulinum in infantile botulism; CSF for albuminocytologic dissociation in Guillain–Barré syndrome; serum acetylcholine receptor or muscle-specific tyrosine kinase antibodies for myasthenia gravis (1,2)[A].
• Blood microarray and chromosomal studies for Down's syndrome, Prader–Willi syndrome, and other chromosomal disorders (1,2)[A].

Imaging

Initial Approach

Cranial ultrasound study may be necessary at the bedside for neonatal birth asphyxia when MRI is impossible because of the intubation and respiratory support of critically sick and unstable neonates.

Follow-Up & Special Considerations

Cranial MRI may detect intracranial ischemia or hemorrhage, increased T2 density of the white matter in the adrenoleukodystrophy or metachromatic leukodystrophy, periventricular calcification for congenital cytomegalovirus infection, diffuse intracranial calcification in congenital toxoplasmosis, and a variety of other brain anomalies. In mitochondrial encephalomyopathy, it may reveal basal ganglia calcification or cerebral or cerebellar atrophy.

Diagnostic Procedures/Other

For lower motor neuron diseases:

• Electromyography is abnormal in the muscle diseases. Motor and sensory nerve conduction velocity study is useful in the evaluation of peripheral neuropathy (1)[A].
• Muscle or nerve biopsy may be indicated if there is evidence of myopathy or neuropathy and for more specific diagnosis of the muscle disorders and neuropathy. Muscles may be examined for the specific histochemical staining and special enzymes’ studies for Pompe's disease, mitochondrial myopathy, specific congenital myopathies, muscular dystrophies, molecular genetic studies, and other studies (1)[A].
• Repetitive nerve stimulation with low frequency (2–3 Hz) often induces decremental response in myasthenia gravis, whereas stimulation with higher frequency (20–50 Hz) often induces incremental response in infantile botulism or Lambert–Eaton myasthenic syndrome (1)[A].
• Edrophonium (tensilon) IV infusion rapidly and dramatically improves the clinical features of myasthenia gravis, such as ptosis, extraocular ophthalmoplegia, and generalized weakness (1)[A].

Pathological Findings

Varies depending on the underlying conditions.

DIFFERENTIAL DIAGNOSIS

• Hypotonia with prominent weakness (lower motor unit disorders): Spinal muscular atrophy, congenital myotonic dystrophy, congenital muscular dystrophy, neonatal myasthenia gravis, congenital myasthenic syndrome, congenital myopathies, metabolic myopathies (Pompe's disease, mitochondrial myopathy), hereditary motor and sensory neuropathies, Guillain–Barré syndrome, tick paralysis, and infantile botulism
• Hypotonia without prominent weakness
  • Cerebral hypotonia: Perinatal hypoxia, birth trauma, Down's syndrome, Prader–Willi syndrome, Zellweger syndrome, Riley–Day syndrome, neonatal adrenoleukodystrophy, infantile G_M1 gangliosidosis
  • Intrauterine infections (toxoplasmosis, rubella, cytomegalovirus, herpes)
  • Metabolic, endocrine, nutritional problems: Biotinidase deficiency, amino acidosis, organic acidosis, renal tubular acidosis, calcium abnormalities, hypothyroidism, celiac disease, malnutrition
  • Connective tissue disorders: Ehlers–Danlos syndrome, Marfan's syndrome
  • Acute illness
  • Benign congenital hypotonia

[Outline]

• History
• Physical Exam
• Diagnostic Tests and Interpretation
  • Lab
    • Initial Lab Tests
    • Follow-Up & Special Considerations
  • Imaging
    • Initial Approach
    • Follow-Up & Special Considerations
  • Diagnostic Procedures/Other
  • Pathological Findings
• Differential Diagnosis

MEDICATION

First Line

Intravenous immunoglobulin is easier to give to infants with Guillain–Barré syndrome. Intramuscular neostigmine given 30 minutes before feeding is useful for neonatal myasthenia gravis. Biotin is indicated for biotinidase deficiency. Thyroid hormone replacement is necessary for hypothyroidism (1,2)[A].

Second Line

Plasma exchange may be useful if intravenous immunoglobulin fails to improve Guillain–Barré syndrome. Pyridostigmine or prednisone may be alternative drugs for myasthenia gravis (1,2)[A].

ADDITIONAL TREATMENT

General Measures

Specific treatment depends on the underlying cause of hypotonia. For example, myasthenia gravis patients require anticholinesterase such as pyridostigmine or neostigmine. Guillain–Barré syndrome may need plasmapheresis or intravenous immunoglobulin or even respiratory support. Hypothyroidism requires treatment with thyroid hormone. Biotin replacement is needed for biotinidase deficiency. Tick paralysis requires removal of the tick from the skin of the patient.

Issues for Referral

When dysmorphic features are noted, genetic referral is needed. For neuromuscular disorders, referral to neuromuscular specialists is needed. For epilepsy, referral to neurologist or epileptologist is needed.

Additional Therapies

Physical, occupational, speech, and language therapy may be helpful when poor fine motor coordination, muscle weakness, and language delay are present.

COMPLEMENTARY AND ALTERNATIVE THERAPIES

Feeding problems may need special nipples, small and frequent feedings, gavage feedings, or even gastrostomy tube. Postural drainage, suctioning, or vigorous respiratory therapy would be necessary if hypotonia and muscle weakness impair cough reflex or pulmonary functions. Stool softener, laxatives, or dietary control may help constipation. Early infant intervention provides useful stimulation.

SURGERY/OTHER PROCEDURES

Gastrostomy tube placement and Nissen fundoplication may be required if the patients have severe feeding problems and gastroesophageal reflux. Tenotomy and tendon transfer or lengthening may be useful for the routine daily care of the patients.

IN-PATIENT CONSIDERATIONS

Initial Stabilization

Respiratory distress from muscle weakness or prolonged seizures may require stabilization at emergency department before admission.

Admission Criteria

Patients may need admission for treatment of prolonged seizures or acute evaluation and treatment of severe weakness associated with hypotonia such as spinal muscular atrophy, congenital muscular dystrophy, neonatal myasthenia gravis, mitochondrial encephalomyopathy, and infantile botulism.

IV Fluids

Infants with feeding difficulty may need IV fluid and nutritional support.

Nursing

Infants with respiratory problems or unstable vital signs may require intensive nursing care.

Discharge Criteria

Once acute weakness improves, vital signs are stable, and there is no need for respiratory support, IV fluid, and nursing care; patients can be discharged.

[Outline]

• Medication
  • First Line
  • Second Line
• Additional Treatment
  • General Measures
  • Issues for Referral
  • Additional Therapies
• Complementary And Alternative Therapies
• Surgery/Other Procedures
• In-Patient Considerations
  • Initial Stabilization
  • Admission Criteria
  • IV Fluids
  • Nursing
  • Discharge Criteria

FOLLOW-UP RECOMMENDATIONS

Patients should be followed regularly after the underlying cause of hypotonia is identified.

Patient Monitoring

Patients with hypotonia may have progressive joint contractures or scoliosis and need proper treatment, such as physical therapy or braces. Other problems, such as seizures, may develop and require antiepileptic drug treatment.

DIET

Ketogenic diet may be needed for intractable epilepsy; gluten-free diet for celiac disease.

PATIENT EDUCATION

Many organizations associated with individual diseases exist to help support patients and their families and research to bring best treatments to the patients.

PROGNOSIS

The clinical course and prognosis depend on the underlying diseases of hypotonia.

COMPLICATIONS

Persistent muscle weakness may occur in severe Guillain–Barré syndrome or other severe neuromuscular disorders; cerebral palsy, mental retardation, and epilepsy may occur in severe perinatal hypoxic infants or other genetic syndromes.

[Outline]

• Follow-Up Recommendations
  • Patient Monitoring
• Diet
• Patient Education
• Prognosis
• Complications

ICD9

781.99 Other symptoms involving nervous and musculoskeletal systems

• Hypotonia with severe muscle weakness indicates lower motor unit disorders.
• Hypotonia without prominent weakness is seen with upper motor unit disorders, connective tissue disorders, chromosomal disorders, acute or chronic systemic illnesses.
  • Mixed hypotonia may be present.

1. Bodensteiner JB. The evaluation of the hypotonic infant. Semin Pediatr Neurol 2008;15(1):10–20.
2. Peredo DE, Hannibal MC. The floppy infant: evaluation of hypotonia. Pediatr Rev 2009;30:e66–e76.