Pediatrics

The floppy infant

OVERVIEW: What every practitioner needs to know

Are you sure your patient has hypotonia? What are the typical findings for this disease?

Signs of Hypotonia

  1. Baby lies in frog leg position with hips abducted and externally rotated

  2. Marked head lag in pull to sit

  3. Inverted "U" position when held in horizontal suspension

  4. "Slip through " with baby held under the axillae in vertical suspension

  5. Decreased resistance to passive movement

  6. Scarf sign

Hypotonia vs. Weakness

It is important to determine if a floppy baby is hypotonic or truly weak. The majority of hypotonic babies are not weak. A weak baby may have physical exam findings such as a high arched palate, "fish mouth" or inverted V appearance of the upper lip, eye lid closure weakness or ptosis, a weak suck and cry, a bell-shaped chest, diminished deep tendon reflexes, decreased muscle bulk, decreased spontaneous movement, or arthrogryposis. Features such as transverse palmar creases, joint laxity, and deep longitudinal plantar creases are non-specific findings.

Encephalopathy is the usual cause of hypotonia without weakness. Decreased level of alertness or alteration in mental status and diminished responses to external stimuli (visual and auditory), poor feeding due to uncoordinated suck and swallow, and brisk deep tendon reflexes are typical findings in these babies. Past infancy, if an intellectual developmental delay is diagnosed, a central nervous system cause of hypotonia is likely.

Central vs. Peripheral Causes of Hypotonia

Signs of central nervous system involvement

  1. Encephalopathy

  2. Seizures

  3. Dysmorphic features

  4. Micro- or macrocephaly

  5. Brisk deep tendon reflexes

Signs of peripheral nervous system involvement

  1. Muscle weakness

  2. Diminished deep tendon reflexes

  3. Fasciculations

  4. Muscle atrophy

What other disease/condition shares some of these symptoms?

  • Central Nervous System Malformation

  • Neuromuscular Disorder

  • Collagen Elastin or Connective Tissue Disorder

  • Metabolic Disorder

  • Genetic Disorder

  • Sepsis

  • Medication/toxin effects

  • Hypoxic-ischemic events

What caused this disease to develop at this time?

Central causes

  • hypoxic-ischemic injury

  • brain malformation

  • sepsis

  • genetic/chromosomal rearrangements

  • metabolic disorders (hypoglycemia, hypothyroidism, calcium abnormalities, inborn errors of metabolism, hyperammonemia, storage disorders)

  • toxin/medication effect (medications causing CNS sedation such as barbiturates or benzodiazepines)

  • perinatal medication exposures (such as maternal medications given during labor and delivery)

Peripheral causes

  • motor neuron disorders (spinal muscular atrophy)

  • neuropathy (inherited neuropathies)

  • neuromuscular junction disorders (infantile botulism, neonatal myasthenia gravis)

  • myopathy/muscular dystrophy (congenital myotonic dystrophy, congenital myopathies, congenital muscular dystrophy)

A careful history and physical exam findings can typically help to determine whether the cause of hypotonia is central or peripheral.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Laboratory testing may be helpful once localization of the etiology has been made (i.e., central or peripheral). The suggested list of laboratory work is not comprehensive but provides a first tier of screening for etiologies of hypotonia.

  • Creatine kinase (CK)--might be elevated due to maternal CK just after birth. If persistently elevated after 2 weeks, consider further evaluation for muscle disorders

  • EMG/NCS) --may be limited in the newborn given the size of the patient, but may distinguish patients with spinal muscular atrophy.

  • Muscle biopsy--this invasive test is reserved for those patients in whom a diagnosis is not possible using clinical exam, genetic testing, imaging studies or laboratory evaluation. Muscle biopsies should be taken from the quadriceps or vastus lateralis muscle.

  • Metabolic screening if the patient has hyperammonemia, seizures, encephalopathy, excessive irritability. Screening may include, but is not limited to, serum amino acids, urine organic acids, lactate, pyruvate, ammonia, acylcarnitine, electrolytes including glucose, calcium, and magnesium. Consider cerebrospinal fluid (CSF) lactate if metabolic disorder is suspected. Specific studies can be ordered, such as very long chain fatty acids or lysosomal enzymes if clinical index of suspicion for these disorders is high.

  • Thyroid function studies--typically included on newborn screen, but should be repeated if hypothyroidism is suspected.

  • An EEG is useful to help determine if an encephalopathy is present.

  • If sepsis is suspected, perform a lumbar puncture with WBC, RBC, protein and glucose; CSF cultures and blood and urine cultures.

  • Genetic testing. If patient has dysmorphic features consistent with Down syndrome, do high-resolution chromosomes. If patient has exam findings consistent with spinal muscular atrophy, do gene testing for deletion of exons 7 and 8 on chromosome 5, If patient has myotonic dystrophy phenotype, do DM1 genetic mutation analysis for CTG repeat number. If patient has dysmorphic features consistent with Prader-Willi syndrome, do fluorescence in situ hybridization (FISH) testing for a 15q deletion, or methylation studies. If patient has dysmorphic features, consider a microarray and genetic consult.

Would imaging studies be helpful? If so, which ones?

  • Cranial ultrasound: widely available, no radiation exposure, no sedation required. Helpful to diagnose a major brain malformation.

  • Cranial MRI: available in most hospitals, no radiation exposure, sedation may be required, difficult to interpret for non-pediatric radiologists, best modality for structural lesions and leukodystrophies.

  • CT scan: widely available, radiation exposure, helpful for blood products and intracranial calcification, which can be associated with some congenital infections.

  • Abdominal ultrasound: if the patient has a suspected metabolic disorder and has organomegaly on clinical examination.

If you are able to confirm that the patient has hypotonia, what treatment should be initiated?

  • Treatment for hypotonia and a floppy baby is dependent on the cause. For example, if the cause of hypotonia is sepsis, then antivirals or antimicrobials should be started immediately. If the baby is hypoglycemic, glucose replacement should be instituted immediately. If the baby is very weak in the newborn period, respiratory insufficiency should be assessed and treated. In weak or very hypotonic infants, nippling and oral feeding is frequently affected. Babies should be assessed to make certain they are not at risk for aspiration. In some circumstances, nasogastric feeds or gastrostomy tubes are needed.

  • Long-term treatment is dependent on the cause of hypotonia as well. Usually physical therapy is instituted early on, and progress is monitored. If the baby has oral motor difficulty and problems with feeding, then occupational or speech therapy may be helpful. Therapies are usually supportive.

  • Counseling should be provided when a specific diagnosis is made. This is particularly important when a diagnosis is made that is life-limiting, such as spinal muscular atrophy, complex congenital brain malformation or severe hypoxic ischemic encephalopathy. A genetic counselor or geneticist should be consulted and provide counseling regarding natural history and recurrence risks of disorders such as Down Syndrome, Myotonic Dystrophy, Spinal Muscular Atrophy, Prader-Willi Syndrome.

What are the adverse effects associated with each treatment option?

N/A

What are the possible outcomes of hypotonia?

Outcomes for hypotonia depend on the cause. Typically, benign hypotonia will improve over time as the child grows. An infant who is initially hypotonic due to hypoxic brain injury will usually develop increasing spasticity, cerebral palsy, and cognitive impairment. Hypotonia due to a collagen elastin disorder will usually improve with age. The natural history of hypotonia in genetic disorders is variable. Adolescents with Down syndrome remain hypotonic, while children with Prader-Willi usually improve. Weakness has a different prognosis depending on the specific diagnosis. In some cases, such as spinal muscular atrophy presenting in early infancy, the weakness is rapidly progressive and life-limiting. In myotonic dystrophy, weakness is usually slowly progressive into adulthood. Parents should be counseled on outcomes specific to the diagnosis.

What causes this disease and how frequent is it?

N/A

How do these pathogens/genes/exposures cause the disease?

N/A

Other clinical manifestations that might help with diagnosis and management

N/A

What complications might you expect from the disease or treatment of the disease?

Hypotonic children are typically slower to develop gross motor milestones. They sometimes appear less coordinated when running or performing complex gross motor tasks. Hyperextensibility is increased range of joint movement or joint laxity. Hyperextensible infants and children are at increased risk of sprains, strains and joint dislocation. In certain connective tissue disorders causing hyperextensibility in children, wound healing is affected and scars may appear dystrophic.

Are additional laboratory studies available; even some that are not widely available?

N/A

How can this disease be prevented?

N/A

What is the evidence?

Aydinli, N, Baslo, B, Calickan, M. "Muscle ultrasonography and electromyography correlation for evaluation of floppy infants". Brain Dev. vol. 25. 2003. pp. 22-4.

This prospective study evaluated the correlation between muscle ultrasound and electromyography in the diagnostic evaluation of hypotonia. The authors found that these were complementary studies, but neither will provide a definitive diagnosis. However, both studies are both safe. In particular, ultrasound is a rapid, noninvasive study that can distinguish between a peripheral and a central etiology for hypotonia.

Birdi, K, Prasad, AN, Prasad, C. "The floppy infant: retrospective analysis of clinical experience (1990-2000) in a tertiary care facility". J Child Neurol. vol. 20. 2005. pp. 803-8.

Bodensteiner, JB. "The evaluation of the hypotonic infant". Semin Pediatr Neurol. vol. 15. 2008. pp. 10-20.

This is a comprehensive review of the etiologies of hypotonia in the infant.

Cheung, SW, Shaw, CA, Yu, W. "Development and validation of a CGH microarray for clinical cytogenetic diagnosis". Genet Med. vol. 7. 2005. pp. 422-32.

This article discusses the utility and the difficulties with interpretation of CGH microarray.

David, WS, Jones, HR. "Electromyography and biopsy correlation with suggested protocol for evaluation of the floppy infant". Muscle Nerve. vol. 17. 1994. pp. 424-30.

This article discusses the utility of EMG and biopsy in the evaluation of the hypotonic infant and a logical algorithm for ordering these procedures.

Dubowitz, V. The floppy infant. JB Lippincott. 1980.

This is still one of the best references available on this topic. Very clinically based with pictures and practical information regarding hypotonic infants

Laugel, V, Cossée, M, Matis, J. "Diagnostic approach to neonatal hypotonia: retrospective study on 144 neonates". Eur J Pediatr. vol. 167. 2008. pp. 517-523.

This is a retrospective study of 144 infants in a single center.

Prasad, AN, Prasad, C. "Genetic evaluation of the floppy infant". Semin Fetal Neonatal Med. vol. 16. 2011. pp. 99-108.

This article provides a diagnostic algorithm for genetic testing based on clinical evidence from published studies.

Rabie, M, Jossiphov, J, Nevo, Y. "Electromyography (EMG) accuracy compared to muscle biopsy in childhood". J Child Neurol. vol. 22. 2007. pp. 803-8.

This retrospective study demonstrates the utility and accuracy of EMG in the evaluation of the hypotonic infant. EMG has a high detection rate for neuropathies and neuromuscular junction defects as an etiology of hypotonia, but has a low detection rate for myopathies.

Richer, LP, Shevell, MI, Miller, SP. "Diagnostic profile of neonatal hypotonia: an 11-year study". Pediatr Neurol. vol. 25. 2001. pp. 32-7.

In this retrospective study, the etiologies of neonates presenting with hypotonia were reviewed. The majority of patients had a genetic or metabolic etiology of their hypotonia.

Ongoing controversies regarding etiology, diagnosis, treatment

N/A

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