Today, I reviewed and excerpted from Approach to Neonatal Hypotonia, by Nikytha.Antony, Sep 14, 2019 from PedsCases.
All that follows is from the above resource.
This podcast covers neonatal hypotonia, including definition, initial presentation, history, physical exam, common causes, and investigations. This podcast was created by Dr. Nikytha Antony, a Pediatrics resident at the University of Calgary, in collaboration with Dr. David Callen, a Pediatric Neurologist at the McMaster Children’s Hospital and Dr. Kim Smyth, a Pediatric Neurologist at the University of Calgary.
From the script:
Case Presentation
Let’s start with a clinical case. You are a learner doing a rotation in the Neonatal
Intensive Care Unit. Your preceptor tells you that there is a 2-day-old who was found to have hypotonia. They ask you to assess the infant and determine the etiology of the hypotonia. What is your approach to this clinical presentation? What do you need to think about on your differential for neonatal hypotonia?The hypotonic newborn or “floppy baby” has a vast list of potential etiologies. Hopefully by the end of this podcast, you will have a basic approach to the differential diagnosis for this presentation.
Differential Diagnosis
The differential for neonatal hypotonia is vast. It really helps to split things up the differential into categories. We will discuss the differential using 3 main categories: 1) Systemic illness, 2) neurological disorders and 3) metabolic/genetic conditions.
Systemic illness, sepsis/infection, metabolic crises and electrolyte disturbances such as hypokalemia, hypophosphatemia, hypocalcemia, hypo or hypernatremia can alsoinitially present with hypotonia so it is important to rule out conditions such as meningitis or organ failure. This fact makes it imperative that a child’s general health is assessed first in the assessment of hypotonia.
Neurological etiologies can be differentiated into central or peripheral causes of hypotonia. The term “central” refers to problems within the central nervous system, including the brain and spinal cord, whereas “peripheral” refers to problems in a
component of the peripheral nervous system, including the anterior horn cell, nerve, neuromuscular junction, and muscle.Infants with central hypotonia are often “floppy, but strong”. They present with a hypotonic posture, but may be able to respond with near appropriate power to applied external stimuli. They may be hyper-reflexic or have normal reflexes and often show other central nervous system abnormalities such as decreased level of consciousness, seizures, apneas and feeding difficulties, and possible abnormalities on head circumference measurements (2).
Infants with central hypotonia are often “floppy, but strong”. They present with a hypotonic posture, but may be able to respond with near appropriate power to applied external stimuli. They may be hyper-reflexic or have normal reflexes and often show other central nervous system abnormalities such as decreased level of consciousness, seizures, apneas and feeding difficulties, and possible abnormalities on head circumference measurements (2).
Infants with peripheral hypotonia are “floppy and weak”. They are often found in a “frog leg” type posture with both lower legs wide open on the bed and have a very limited motor response to applied external stimuli. They may demonstrate normal or
hyporeflexia and may have diffusely low muscle bulk and/or multiple congenital contractures. Despite this, they are “centrally bright” with preservation of alertness and
consciousness (2).An example of a cause of peripheral hypotonia is spinal muscular atrophy (SMA). This genetic condition causes the degeneration of the anterior horn cells and thus causes motor deficit with no sensory involvement. The most common type in newborns is SMA type 1 which is also known as Werdig-Hoffman disease. This condition is characterized by profound symmetric proximal muscle weakness that is greater in the lower limbs along with decreased or absent deep tendon reflexes. Sometimes fasciculations of the muscles, including the tongue can be seen. SMA is typically diagnosed by genetic testing.*
*Please see Advances in Treatment of Spinal Muscular Atrophy – New Phenotypes, New Challenges, New Implications for Care [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. J Neuromuscul Dis. 2020;7(1):1-13. doi: 10.3233/JND-190424.
Myasthenia gravis is an example of a neuromuscular defect leading to peripheral hypotonia. It is an autoimmune illness. Newborns with myasthenia gravis present with
global hypotonia and/or feeding and respiratory difficulties or apneas. In adults myasthenia gravis is typically an acquired autoimmune disorder where the body creates
antibodies against the acetylcholine receptors, which inhibits neuromuscular transmission. In neonates the cause can either be transient due to antibodies from a
mother with myasthenia gravis passing through to the baby (transient neonatal myasthenia gravis), or genetic due to mutations in genes that produce proteins that function within the neuromuscular junction such as the acetylcholine receptor
(congenital myasthenia). Myasthenia gravis is diagnosed through detection ofantibodies to the acetylcholine receptor in the blood, repeated nerve stimulation tests, through clinical response to the anticholinesterase inhibitor, neostigmine, or via specific molecular genetic testing (for congenital forms). (5)Muscle disorders, such as congenital myopathies or muscular dystrophies can also cause neonatal hypotonia.
The third and final category is genetic and metabolic causes. Some genetic syndromes that can present with hypotonia include Prader-Willi syndrome and Down syndrome.
Inborn errors of metabolism can also present with newborn hypotonia. It is important to note that combined genetic and metabolic causes make up about 60% of the causes for a floppy baby (2).Prader-Willi syndrome is a genetic condition that occurs due to the loss of expression of paternal genes on chromosome 15. Typical clinical features in the newborn period include hypotonia and feeding difficulties. Classic physical features include almond shaped eyes, small hands and feet, thin upper lip and hypogonadism. For diagnosis, a DNA based test is required such as a methylation study using polymerase chain reaction (PCR). (4)
Many other genetic conditions, such as Down Syndrome, and chromosome deletion and duplication syndromes also present with neonatal hypotonia.
Physical exam
With all exams, start with a general assessment of the child, including vital signs and level of consciousness. Looking for signs of systemic illness, ensure the child is not unwell as hypotonia can be the first sign of sepsis or a metabolic deterioration.*
*And begin stat evaluation and treatment.
Specifically, when assessing tone, there are three tests that should be done when possible (i.e. if baby is well enough, not intubated) (7):
1) Horizontal suspension – support the baby with one hand on the chest. Normally, the baby should make an attempt to hold its head up and keep the spine straight. If the baby has low tone, you will notice an inverted U shape as the baby rests
against your hand since the baby will make no attempt to straighten out the spine or keep its head up.2) Vertical suspension – Support the baby with two hands under the armpits and lift up vertically. Normally, the baby will have its arms flexed so that it does not fall
out of the examiner’s hand but a baby with hypotonia will slip through the examiner’s hands.3) Traction Response – Hold both of the newborn’s arms with each hand and lift up from the supine position. Normally, the baby older than 3 months will attempt to lift up its head as well as it is lifted by the arms but a floppy baby will have significant head lag.
Investigations
For systemic illness, initial investigations should be conducted to rule out lifethreatening and reversible causes, which include a full septic workup, electrolytes including magnesium and calcium, liver function tests, ammonia and lactate.
For infants with neurological causes of hypotonia, such as risk factors for HIE or signs of central causes of hypotonia, such as lethargy, upper motor neuron signs, or seizures, an MRI of the brain +/- EEG should be completed. In infants with peripheral hypotonia, a creatinine kinase, electromyography/nerve conduction study, and potentially a muscle biopsy could be considered.
For genetic/metabolic causes, additional specialized testing may be needed, including genetic screen through karyotype and microarray analysis depending on the dysmorphic features and congenital anomalies displayed. Specific genetic testing for
disorders such as Prader Willi Syndrome or SMA should also be considered based on the clinical presentation. It is important to get additional specialists involved early, particularly pediatric neurologists.Summary:
Before we finish, let’s leave with a few key take-home points.
1) Neonatal hypotonia is defined as poor muscle tone in the trunk, upper and lower limbs and face.
2) A complete prenatal, birth and postnatal history is essential along with a through physical examination placing special attention on the neurological examinationand special tests for hypotonia.
3) The differential diagnosis includes 3 main categories: 1) systemic illness likeinfection or electrolyte abnormalities, 2) neurologic disease such as central hypotonia stemming from cortical or brainstem deficits or peripheral causes stemming from stemming from anterior horn cell or neuromuscular junction or muscles, and 3) genetic, chromosomal and metabolic abnormalities.
