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Hi my name is Dr. Nikytha Antony and I am currently a Pediatrics resident at the University of Calgary. This podcast will review an approach to neonatal hypotonia, or the “floppy baby.” This podcast was done 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.
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.
Tone is defined as muscle’s intrinsic resistance to passive stretch. Tone is distinct from strength or power, which is a measure of how much force a muscle can generate. Neonatal hypotonia is defined as poor muscle tone in the muscles of the trunk, limbs and face (1). This means that the muscles provide little resistance when someone else is passively moving them. In contrast, a patient with increased tone would have spasticity or rigidity. Hypotonia can be categorized as axial or truncal, predominantly
affecting the neck and spinal muscles; appendicular, affecting predominantly the extremities; or global, affecting the entire body. It is identified early in life when the newborn is unable to obtain a normal posture during movements or at rest. (1)
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 also initially 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).
An example of a central cause for hypotonia would be hypoxic-ischemic
encephalopathy or HIE. This condition is caused by the brain not receiving enough oxygen to function for a period of time. Usually there is clear evidence correlating the event and the subsequent neurological sequelae and the degree of hypotonia can vary based on the severity of the injury to the brain. (6) Other causes of central hypotonia include malformations of brain development and vascular events such as intracranial bleeds or strokes.
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
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.
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 of antibodies 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)
May other genetic conditions, such as Down Syndrome, and chromosome deletion and duplication syndromes also present with neonatal hypotonia.
Initially on history you will want to assess the timing and the progression of the hypotonia. Was it present at birth, or did it evolve over time? Is it getting better or is it getting worse? Depending on the age of the child you can ask about developmental milestones, and see if the child is attaining appropriate gross motor and fine motor skills.
A thorough prenatal, birth and neonatal history of the newborn is essential in order to determine the cause of hypotonia.
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.
So given that the differential diagnosis for a newborn with hypotonia is vast, the potential diagnostic workup can be extensive and hence should be guided by your history and physical examination.
For systemic illness, initial investigations should be conducted to rule out life-threatening 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.
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 examination and special tests for hypotonia.
3) The differential diagnosis includes 3 main categories: 1) systemic illness like infection 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.