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NEUROLOGY SUBSPECIALTY ARTICLE
A schematic approach to hypotonia in infancy
JoAnna Leyenaar MD MPH, Peter Camfield MD FRCPC, Carol Camfield MD FRCPC
J Leyenaar, P Camfield, C Camfield. A schematic approach
to hypotonia in infancy. Paediatr Child Health 2005;
10(7):397-400.
Hypotonia may be the presenting sign for many systemic diseases and
diseases of the nervous system. The present paper discusses a rational,
simple and accurate diagnostic approach to hypotonia in infancy,
illustrated by the case of a five-month-old infant girl recently referred
to the IWK Health Centre in Halifax, Nova Scotia. Key points in the
history and physical examination are outlined to allow a tailored
investigation both for the patient and for other hypotonic infants. A
discussion of an important neuromuscular disease, diagnosed in the
present patient, concludes the paper.
Key Words: Hypotonia; Infant; Spinal muscular atrophy
nfants with hypotonia pose challenges for clinicians
I because hypotonia may be the presenting sign of both
benign and serious conditions. On first glance, the magni-
tude of the differential diagnosis, the rarity of associated ill-
nesses, and the ongoing advances in diagnosis and
management may appear overwhelming.
The present paper discusses a practical approach to
hypotonia in infancy. Key elements in the child’s develop-
mental and medical history and physical examination are
outlined. The case of a five-month-old infant girl, recently
seen at the IWK Health Centre in Halifax, Nova Scotia,
provides a basis for discussion.
CASE PRESENTATION
A five-month-old infant girl was brought to her family
physician after a family friend expressed concern that she
was unable to raise her upper body when lying prone. Her
parents stated that she had made no attempts to roll over,
rarely moved her legs and made no attempts to push with
her feet when held upright. She put toys into her mouth
using both hands but did not reach farther than 10 cm for
objects before her. She laughed and interacted with those
around her and became excited at the sight of food. She
breastfed well and seemed to have tolerated the recent
introduction of rice cereal without coughing, choking or
vomiting. She often squealed and seemed to respond to her
name. No loss of milestones was reported.
She had been born at 38 weeks by spontaneous vaginal
delivery with no prenatal or postnatal concerns. Apgar
scores were 8 at 1 min and 5 min, with points lost for colour
and tone. At three months, she had been hospitalized for
Department of Pediatrics, Dalhousie University, IWK Health Centre, Halifax, Nova Scotia
Correspondence: Dr Peter Camfield, IWK Health Centre, 5850 University Avenue, PO Box 3070, Halifax, Nova Scotia B3J 3G9.
Telephone 902-470-8479, fax 902-470-8486, e-mail camfield@dal.ca
Paediatr Child Health Vol 10 No 7 September 2005
Une démarche schématique envers l’hypotonie
pendant la première enfance
L’hypotonie peut être le signe révélateur de nombreuses maladies
systémiques ou du système nerveux. Le présent article traite d’une
démarche diagnostique rationnelle, simple et précise envers l’hypotonie
pendant la première enfance, illustrée par le cas d’une fillette de cinq mois
récemment aiguillée vers le IWK Health Centre de Halifax, en Nouvelle-
Écosse. Les principaux points de l’anamnèse et de l’examen physique sont
exposés afin de permettre une exploration personnalisée de la patiente et
des autres nourrissons hypotoniques. Un exposé sur une importante
maladie neuromusculaire, diagnostiquée chez la patiente, conclut l’article.
respiratory syncytial virus-positive bronchiolitis. The family
history was unremarkable and there was no consanguinity.
The infant’s mother had antiphospholipid syndrome. There
was a seven-year-old, healthy male sibling.
On examination, the infant looked well, with no dys-
morphic features. Height, weight and head circumference
were between the 75th and 90th percentiles. She had a
strong cry and no fasciculations of the tongue were noted.
Respiratory, cardiovascular and abdominal examinations
were normal. Cranial nerves were normal, including
extraocular movements. She had marked hypotonia on hor-
izontal and vertical suspension. Tightness of the hip adduc-
tors and knee extensors was noted. She had a weak grasp
and was unable to reach forward. Primitive reflexes were
absent. Deep tendon reflexes could not be elicited.
Step 1: Understanding the terminology
A key distinction is to determine whether the infant has
low tone with or without muscle weakness. Tone is
defined as the resistance of muscles to stretch (1); there-
fore, hypotonia is diminished resistance of muscles to pas-
sive stretching. With respect to infantile hypotonia, it
may be considered the “least resistance that an alert (but
not overstimulated) infant generates while opposing pas-
sive movement” (2). In contrast, weakness is diminished
muscle power or strength. While weak infants are always
hypotonic, hypotonia is often present with normal
strength (2).
Hypotonia is caused by disorders that affect any level of
the nervous system – brain, brain stem, spinal cord, periph-
eral nerves, neuromuscular junction and muscle. Figure 1
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Leyenaar et al
Nerve
• Congenital
hypomyelinating
neuropathy
• Familial dysautonomia
• Infantile neuraxonal
Central Nervous
System
degeneration
• Chromosome
disorders (ie.
Prader-Willi) . a variety of disorders with prenatal onset, developmental
• Metabolic diseases . Muscle
• Spinal cord injuries
• Cerebral
dysgenesis
Motor
Neuron
• Hypoxic-ischemic
• Spinal
injuries
muscular
atrophies
Neuromuscular Junction
• Congenital and transient
myasthenia gravis
• Infantile botulism
Figure 1) Anatomical-clinical correlation illustrating differential diag-
nosis of hypotonia in infancy
illustrates common diseases with hypotonia as a prominent
feature and their anatomical correlates.
The term ‘benign congenital hypotonia’ was historically
used as a diagnosis for infants who were hypotonic in the
absence of other signs and symptoms, and who had normal
tone in later childhood. We urge caution in the use of this
‘diagnosis of exclusion’, especially because it requires many
months of follow-up for confirmation. One author argues
that benign congenital hypotonia has not been an appropri-
ate diagnosis since the 1960s, when central core disease and
a number of other congenital myopathies were described (3).
Step 2: Key elements in the patient’s history
Although the list of conditions to be considered in the dif-
ferential diagnosis of hypotonia in infancy is long, the
patient’s history may narrow the possibilities significantly.
Details of the pregnancy, delivery and postnatal period are
important – a history of preterm delivery; toxoplasmosis,
other infections, rubella, cytomegalovirus infection and
herpes simplex; neonatal seizures; drug and alcohol use; or
other pre- or postnatal insult increases the probability of
central nervous system (CNS) dysfunction as the underly-
ing etiology for low tone. A history of hip subluxation or
arthrogryposis increases the likelihood of hypotonia in
utero (1). Inborn errors of metabolism should be suspected
in an infant with a normal pregnancy and delivery and the
development of hypotonia after the first day or two of life.
A developmental assessment is useful. Motor delay with
normal social and language development decreases the like-
lihood of brain pathology. In contrast, loss of milestones
increases the index of suspicion for neurodegenerative disor-
ders. A dietary/feeding history may point to diseases of the
neuromuscular junction, which may present with sucking
and swallowing difficulties that ‘fatigue’ or ‘get worse’ with
repetition. Several genetic disorders may present with hypo-
tonia, including Prader-Willi syndrome, which in later
childhood shows hypotonia, obesity, mental retardation and
hypogonadism but is characterized in infancy by feeding
398
difficulties and failure to thrive. Therefore, a detailed feeding
history from birth may provide valuable diagnostic clues. A
diagnosis of infantile botulism may be prompted by a history
of honey or corn syrup consumption; contamination of these
products with Clostridium botulism may account for up to 20%
of botulism cases during infancy (1). The family history may
be very revealing: a history of repeated abortions may suggest
• Muscular delay (a chromosomal abnormality), delayed motor mile-
dystrophies
• Metabolic stones (a congenital myopathy) and premature death (meta-
myopathies
• Central core
bolic or muscle disease).
disease/fibre
myopathies
• Other
congenital
Step 3: The physical examination
myopathies
The physical examination typically narrows the differential
diagnosis markedly. The degree of hypotonia may be initially
inferred by assessing the infant’s posture while supine; truly
hypotonic infants may lie ‘frog-legged’, with hips adducted
and knees flexed. A lack of spontaneous movement suggests
weakness.
In assessing tone, the child should be alert but not cry-
ing. Extremity tone is readily assessed by passive movements.
Truncal and nuchal tone may be best examined using tests of
horizontal and vertical suspension. On vertical suspension, a
healthy infant should maintain the head upright and mid-
line without slipping through the examiner’s hands. On
horizontal suspension, the infant should maintain a straight
back with the head upright and limbs flexed. In contrast,
hypotonic infants may wrap over the examiner’s arms.
While strength may be measured in adults and older
children using a standardized five-point scale, the ability to
point, reach and lift may provide more helpful information
in infants (1). Encouraging the caregiver to become
involved in this portion of the examination may provide
valuable information. Abilities will need to be compared
with age-appropriate developmental norms.
The deep tendon reflexes are likely the most valuable
aspect of the physical examination. Brisk reflexes or clonus
indicate CNS dysfunction, while diminished or absent
reflexes point strongly to disorders of the lower motor unit.
Dysmorphic features sharply increase the likelihood of
CNS dysfunction as an explanation for hypotonia, although
a long, narrow face may indicate muscle weakness. Anterior
horn cell disease usually spares extraocular muscles, while
diseases of the neuromuscular junction may be characterized
by ptosis and extraocular muscle weakness (2). Attention to
the quality of the cry is important because a high-pitched or
unusual-sounding cry suggests CNS pathology, a weak cry
may reflect diaphragmatic weakness, and a fatigable cry may
suggest a congenital myasthenic syndrome.
A head-to-toe physical examination is required to assess
for potentially associated organ dysfunction and to recog-
nize existing syndromes. Abnormalities of internal organs
such as the heart or liver are more likely to be associated
with a number of metabolic diseases. In the presence of
hypotonia, signs of cardiac failure suggest muscle or mito-
chondrial disease. Hepatosplenomegaly suggests a lysosomal
or glycogen storage disease (4).
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Physical examination of the parents may also provide
important diagnostic information, especially because a par-
ent may have very mild symptoms of a serious disorder. For
example, transitory neonatal myasthenia may be suspected
if the mother displays fatiguability of the eyelids with
upward gaze or fatiguability of the arms with sustained for-
ward extension. Infants with congenital myotonic dystro-
phy have severe hypotonia but their mothers are typically
only mildly affected and unaware of their disorder. Mothers
with myotonic dystrophy may show grip myotonia, percus-
sion myotonia, ptosis and/or distal weakness that they were
unaware of. Although myotonic dystrophy is inherited as an
autosomal dominant disorder, when a newborn inherits the
gene and shows the striking weakness and bulbar difficulties
of congenital myotonia, the mother, not the father, is nearly
always affected (5,6).
Step 4: Investigations
The history and physical examination should guide the
investigations. If there is good evidence for CNS dysfunc-
tion, brain imaging may be the first step. Suspicion of meta-
bolic disease will trigger the appropriate tests; an immediate
search for disorders of energy metabolism, amino acid
metabolism, fatty acid metabolism and urea cycle function
should be undertaken immediately if the child presents in
metabolic crisis. These types of disorders may be more read-
ily detected during metabolic crisis than once the child has
been stabilized. The presence of particular dysmorphic fea-
tures may prompt karyotype testing. Screening for hypothy-
roidism should be performed in all infants for whom an
etiology is not clear. If a disorder of the muscles, nerves or
neuromuscular junctions seems likely, a creatine phospho-
kinase (CPK) test may be useful, keeping in mind that most
congenital myopathies are associated with a normal CPK
level, while anterior horn cell disease may be associated
with mild increases. A significant increase in CPK suggests
a form of congenital muscular dystrophy.
Following initial screening tests and noninvasive inves-
tigations, electromyography (EMG), nerve conduction
studies and muscle biopsy may be considered. If muscle
biopsy or EMG are considered, blood for a CPK test should
be drawn before these procedures because the procedures
may cause a short-term elevation of the CPK level (1).
Given the advances in genetic testing, muscle biopsies are
not performed with the same frequency as they were in the
past. Specific genetic tests are available for such disorders as
Prader-Willi and the spinal muscular atrophies (SMAs).
However, many muscular disorders that present with hypo-
tonia in the newborn or infancy period can only be diag-
nosed specifically using a muscle biopsy. Processing of the
biopsy must include sophisticated electron microscopy and
special staining – a ‘routine’ biopsy may miss significant
pathology (7).
REVIEW OF THE CASE
Reviewing our case presentation in the context of the
above discussion and Figure 2, a number of points become
Paediatr Child Health Vol 10 No 7 September 2005
A schematic approach to hypotonia in infancy
History:
Prenatal History: TORCH infections? Drugs or alcohol? Maternal illness? Fetal movements?
Neonatal History: Delivery complications? Preterm delivery? Seizures? Initial presentation of
hypotonia?
Past Medical History: History of presenting symptoms? Associated symptoms? Symptoms of systemic
disease? Rate of symptom progression?
Developmental History: Delayed milestone attainment? Loss of milestones? Motor, social and language
incongruence?
Feeding History: Stamina with feeding? Choking or aspiration? Constipation? Honey or corn syrup?
Family History: Other children? Consanguinity? Developmental delay? Neurological disease?
Premature death? Metabolic or genetic diseases?
General Physical Examination:
Head and neck: Microcephaly? Dysmorphic features? Ptosis? Facial
expression? Nutritional wasting?
Systems: Cardiovascular findings? Liver enlargement? Splenomegaly?
Skeletal abnormalities? Arthrogryposis?
Neurological Examination:
Objective – Localize the lesion.
Cranial nerves: Extraocular movements? Muscles of facial expression? Fasciculations of tongue?
Tone: Posture? Horizontal and vertical suspension? Scissoring or spasticity?
Strength: Proximal versus distal weakness? Symmetry?
Reflexes: Hyperactive? Symmetry? Readily elicited? Clonus?
Muscles: Atrophy? Symmetry?
Motor Neuron Nerve NM Junction Muscle
Tone*
Strength
normal/
normal/
Reflexes
Muscle Atrophy
absent absent normal/
normal/
absent/
normal/
Investigations:
General Investigations: TSH, free T4, electrolytes (including calcium)
CNS Dysfunction Suspected: CT/MRI head, consider EEG, consult neurology, and
consider karyotype
Metabolic Disease Suspected: Urine and serum amino acids, urine organic acids,
blood gas, serum ammonia, liver function tests
Lower Motor Neuron Disease Suspected: Creatine kinase, referral to neurology for
specialized tests
Figure 2) Schematic approach to hypotonia in infancy. Pertinent posi-
tives, highlighted in italics, raise suspicion of central nervous system and
metabolic diseases. ↑ Increased; ↓ Decreased; CNS Central nervous
system; CT Computed tomography; EEG Electroencephalography;
MRI Magnetic resonance imaging; NM Neuromuscular; TORCH
Toxoplasmosis, other infections, rubella, cytomegalovirus infection and
herpes simplex; TSH Thyroid-stimulating hormone. *Adapted from ref-
erence 2
relevant. First, the infant’s social and communication skills
were age-appropriate, while her hypotonia was associated
primarily with marked gross motor delay. This increases the
likelihood of a disorder of the lower motor neuron unit. A
diagnosis of lower motor neuron disease is also supported by
the unremarkable pregnancy and early postnatal course.
The physical examination provides further support: absent
reflexes with decreased strength points decisively to dis-
eases of the motor unit. The absence of ptosis, early severe
feeding difficulties and extraocular muscle weakness suggests
that problems in the neuromuscular junction are unlikely
and increases the likelihood of motor neuron disease.
Given the results of the history and physical examina-
tion, a diagnosis of SMA seemed very likely. EMG con-
firmed dysfunction in the anterior horn cells, and blood sent
for genetic testing confirmed a diagnosis of SMA type 1.
Parents were counselled regarding the nature of the disease
and the value of supportive care.
DISCUSSION
The SMAs are a group of diseases characterized by a pro-
gressive loss of spinal anterior horn cells, leading to muscu-
lar denervation, atrophy and weakness. It is the second most
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Leyenaar et al
common hereditary neuromuscular disease, with a carrier
frequency of one in 50 to one in 80 and an incidence of one
in 10,000 to one in 25,000 (8). The most common forms of
SMA are transmitted by autosomal recessive inheritance,
with the gene defect localized to the motor neuron survival
gene (SMN gene) on chromosome 5q. Rare X-linked and
autosomal dominant forms have been recognized.
SMA type 1, also known as Werdnig-Hoffman disease, is
most commonly described as the acute, infantile form of the
disease, with symptoms recognized within the first six
months of life. Patients with SMA type 1 rarely develop the
ability to sit unassisted and usually die by two years of age
(9). SMA type 2 has intermediate severity, often following a
more chronic course. Patients may be able to sit unassisted,
are generally unable to stand or walk without assistance, but
may survive well into adolescence or young adulthood (10).
SMA type 3, Kugelberg-Welander disease, generally mani-
fests after 18 months of age and follows a slower disease pro-
gression, with survival into adulthood.
Children with SMA type 1 are most frequently per-
ceived by parents to be normal during the first months of
life, with subsequent development of dramatic hypotonia,
proximal muscle weakness and absent deep tendon reflexes.
The disease is not associated with sensory loss or intellectual
impairment. Like our patient, most infants presenting with
SMA type 1 appear normal on first glance because extraoc-
ular movements are spared and muscles of facial expression
relatively so. As weakness develops, fasciculations of the
tongue and fingers may be noted. With disease progression,
feeding and swallowing are compromised, and death usually
results from aspiration and respiratory insufficiency.
Treatment of SMA type 1 is supportive. Although the
disease is generally described as rapidly progressive, the
course may be quite variable. Counselling, respite care,
physiotherapy, occupational therapy and other necessary
supports should be made available.
Several studies have addressed the relative frequency of
the various causes of neonatal/infantile hypotonia
400
(11,12). Cerebral causes predominate and one series (12)
suggested that this group of disorders might explain up to
88% of cases. Prader-Willi syndrome was particularly
important. Paro-Panjan and Neubauer (12) suggested a
six-step approach to diagnosis. Step 1 was simply the clini-
cal examination, which allowed a successful diagnosis in
50% of 138 cases. Step 2 was neuroimaging, which diag-
nosed 13% of cases. Step 3 involved a search for dysmor-
phic syndromes, which diagnosed 9%. Step 4 involved
karyotyping and fluorescence in situ hybridization tests,
which diagnosed an additional 6.5%. Step 5 was made up of
biochemical testing, which diagnosed 6%. Step 6 involved
muscle and/or nerve biopsy, which diagnosed 6%. The
remaining patients were only diagnosed with prolonged
follow-up. Clearly, a careful history and physical examina-
tion will provide most of the clues.
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