THE FLOPPY CHILD CLINICAL APPROACH TO THE FLOPPY CHILD

THE FLOPPY CHILD

CLINICAL APPROACH TO THE
FLOPPY CHILD

The floppy infant syndrome is a well-recognised entity for paediatricians and
neonatologists and refers to an infant with generalised hypotonia presenting at birth
or in early life. An organised approach is essential when evaluating a floppy infant,
as the causes are numerous.

A detailed history combined with a full systemic and neurological examination
are critical to allow for accurate and precise diagnosis. Diagnosis at an early
stage is without a doubt in the child’s best interest.

HISTORY

R van Toorn The pre-, peri- and postnatal history is important. Enquire about the quality and
quantity of fetal movements, breech presentation and the presence of either poly-
MB ChB, (Stell) MRCP (Lond), FCP (SA) or oligohydramnios. The incidence of breech presentation is higher in fetuses
Specialist with neuromuscular disorders as turning requires adequate fetal mobility.
Department of Paediatrics and Child Health Documentation of birth trauma, birth anoxia, delivery complications, low cord
Faculty of Health Sciences pH and Apgar scores are crucial as hypoxic-ischaemic encephalopathy remains
Stellenbosch University and an important cause of neonatal hypotonia. Neonatal seizures and an encephalo-
Tygerberg Children’s Hospital pathic state offer further proof that the hypotonia is of central origin. The onset
of the hypotonia is also important as it may distinguish between congenital and
aquired aetiologies. Enquire about consanguinity and identify other affected fam-
ily members in order to reach a definitive diagnosis, using a detailed family
pedigree to assist future genetic counselling.

Ronald van Toorn obtained his medical CLINICAL CLUES ON NEUROLOGICAL EXAMINATION
degree from the University of Stellenbosch,
and completed his paediatric specialist There are two approaches to the diagnostic problem. The first is based on identi-
training at both Red Cross Children’s fying the neuro-anatomical site of the lesion or insult. The second is to determine
Hospital in Cape Town and the Royal whether or not the hypotonia is accompanied by weakness. Careful neurological
College of Paediatricians in London. One examination should, in most cases, localise the site of the lesion to the upper
of his interests is in the field of neuromus- motor neuron (UMN) or lower motor neuron (LMN) unit. Useful clues are listed in
cular medicine. His working experience Fig. 1.
includes the neuromuscular clinics attached
to Birmingham Children’s, Red Cross Next assess whether the hypotonia is accompanied by weakness. Weakness is
Children’s, Guy’s and St Thomas’ hospitals. uncommon in UMN hypotonia except in the acute stages. Hypotonia with pro-
found weakness therefore suggests involvement of the LMN. Assessment of muscle
power of infants is generally limited to inspection.

Useful indicators of weakness are:
• Ability to cough and clear airway secretions (‘cough test’). Apply pressure to

the trachea and wait for a single cough that clears secretions. If more than
one cough is needed to clear secretions, this is indicative of weakness.2
• Poor swallowing ability as indicated by drooling and oropharyngeal pooling
of secretions.
• The character of the cry — infants with consistent respiratory weakness have
a weak cry.
• Paradoxical breathing pattern — intercostal muscles paralysed with intact
diaphragm.

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Floppy strong Floppy weak

Increased tendon reflexes Hypo- to areflexia
Extensor plantar response Selective motor delay
Sustained ankle clonus Normal head circumference
Global developmental delay and growth
Microcephaly or suboptimal Preserved social interaction
head growth Weakness of antigravitational
Obtundation convulsions limb muscles
Axial weakness a significant Low pitched weak cry
feature Tongue fasciculations
Paradoxical chest wall
Upper motor neuron movement
disorder
Central hypotonia Lower motor neuron
disorder
Peripheral hypotonia

Creatine kinase assay
EMG
Nerve conduction
studies

Genetic studies CT/MRI DNA-based mutation Muscle or nerve
Karotyping analysis if available biopsy
FISH methylation studies
VLCFA

Triosomy 21 Hypoxic ischaemic Spinal muscuar Congenital
Prader-Willi syndrome encephalopathy dystrophy structural
Zellweger syndrome Cerabral malformations Congenital myotonic myopathies
dystrophy
Congenital muscular
dystrophies

Fig. 1. Clinical clues on neurological examination (EMG = electromyogram: CT= computed tomograph; MRI = magnetic
resonance imaging; VLCFA = very long-chain fatty acids; FISH = fluorescent in situ hybridisation)

• Frog-like posture and quality of Further confirmation of the last indica- support with a sensation of ‘slipping
spontaneous movements — poor tor can be obtained by means of infor- through he hands’ during vertical sus-
spontaneous movements and the mal neurological examination in the pension testing and inverted U posi-
frog-like posture are characteristic test positions. Excessive head lag will tion on ventral suspension are further
of LMN conditions. be evident on ‘pull to sit’. Minimal indicators (Fig. 2.1 and 2.2).3

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THE FLOPPY WEAK INFANT The presence of a facial diplegia
(myopathic facies) suggests either a
Table I gives a comprehensive congenital structural myopathy or
approach to the clinical clues and myasthenia gravis. Respiratory and
investigations for the more common bulbar weakness can accompany
phenotypes of the weak floppy infant. both conditions. Fluctuation in strength
would favour myasthenic syndromes
Once the lesion has been localised to (Fig. 6).
the LMN proceed with further neu-
Fig. 2.1. A 12-week-old male infant with roanatomical localisation according to
excessive headlag evident on ‘pull-to-sit’. the compartments of the LMN. The
Note the hypotonic posture of the legs compartments and disease associa-
with external rotation. tions are listed in Fig. 3.

Fig. 2.2. The same infant in horizontal Examine the tongue for size and fasci-
suspension. Note the inverted U posture. culations. Fasciculations, irregular
twitching movements, generally indi-
A distinct pattern of weakness may cate an abnormality of the anterior
favour certain aetiologies: horn cells (Fig. 4). Do not examine the
• Axial weakness is a significant fea- tongue while the infant is crying. The
co-existence of atrophy would strongly
ture in central hypotonia. favour a denervative aetiology. An
• Generalised weakness with sparing ECG may be helpful in demonstrating
baseline fasciculations of the inter-
of the diaphragm, facial muscles, costal muscles (Fig 5). Enlargement of
pelvis and sphincters suggests ante- the tongue may suggest a storage dis-
rior horn cell involvement. order such as Pompe’s disease.
• With myasthenic syndromes, the
bulbar and oculomotor muscles Fig. 6. Ptosis and external ophthalmo-
exhibit a greater degree of involve- plegia in a floppy weak child sugges-
ment. tive of myasthenia gravis.
• Progressive proximal symmetrical
weakness suggests a dystro- Fig. 4. Tongue fasciculations in a child Where clinical evaluation suggests
phinopathy. Signs of proximal with spinal muscular atrophy. The com- complex multisystem involvement (i.e.
weakness in the older infant bination of fasciculations with atrophy hypotonia plus) inborn errors of
include a lordotic posture, is strongly indicative of muscle dener- metabolism should be excluded.
Trendelenburg gait and Gower vation. Referral to a tertiary centre for meta-
sign. bolic investigations would then be
• A striking distribution of weakness indicated.
of the face, upper arms and shoul-
ders suggests fascioscapulohumeral THE FLOPPY STRONG CHILD
muscular dystrophy.
• Distal muscle groups are predomi- The presence of facial dysmorphism
nantly affected with peripheral neu- should alert the doctor to the possibili-
ropathies. Signs suggesting distal ty of an underlying syndrome or genet-
weakness in an older infant would
include weakness of hand grip, Fig. 5. ECG of a floppy infant with spinal muscular atrophy demonstrating base-
foot drop and a high stepping, line fasciculations arising from the underlying intercostal muscles.
slapping gait.

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Anterior horn cell:
Spinal muscular atrophy
Poliomyelitis

Nerve fibre: neuropathies
(Demyelinating or axonal)
Acquired: Guillain-Barré syndrome
Infectious: diphtheria, syphilis, coxsackie, HIV
Toxic: drugs, heavy metals
Nutritional: Vit B1, B6, B12, E, folate
Endocrine: Diabetes, uraemia
Metabolic neurodegenerative causes
Hereditary: Charcot-Marie-Tooth disease

Neuromuscular junction
Myasthenia gravis
Botulism

Muscle
Dystrophinopathies (lack of specific muscle protein):
Duchenne, Becker’s fascioscapular humeral, limb gir-
dle and congenital muscular dystrophies
Congenital myopathies (abnormal muscle structure)
Muscle membrane disorders: congenital myotonias,
congenital myotonic dystrophies
Inflammatory myopathies: dermatomyositis,
poliomyositis
Metabolic myopathies: lipid glycogen storage dis-
eases
Endocrine myopathies: hypothyroidism
Energy depletion within muscle: mitochondrial, free-
fatty acid oxidatation and carnitine disorders

Fig. 3. LMN comportments and disease associations.

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Table I. Clincical clues and investigations of the more common phenotypes of the floppy weak infant

Condition Clinical clues Investigations

Spinal cord transection or Haemangioma or tuft of hair in midline MRI spinal cord
disease Scoliosis
Syringomyelia or other forms Evidence of bladder or bowel dysfunction ECG: Baseline fasciculations
of spinal dysraphism Mixed deep tendon reflexes with absent Deletion of the survival motor
Spinal muscular atrophy abdominal and anal reflexes neuron (SMN) gene by PCR
Tongue atrophy and fasciculations testing
Peripheral neuropathy Paradoxical breathing pattern
Severe proximal muscle weakness with Motor nerve conduction
absent tendon reflexes studies
Preserved social interaction Sural nerve biopsy
Weakness predominantly distal Molecular DNA testing is
In most cases absent deep tendon reflexes available for specific
Pes cavus demyelinating disorders
Response to acethylcholine
Myasthenia gravis Greater involvement of oculomotor and esterase inhibitors
bulbar muscles Single-fibre EMG
Infantile botulism True congenital myasthenia due to receptor Serum antibodies to
Congenital muscular defects is rare acethylcholine receptors
dystrophy Exclude transient neonatal form from Electrodiagnostic studies not
Congenital myotonic maternal history universally positive in young
dystrophy patients
Acute onset descending weakness, Isolation of organism from
Congenital structural cranial neuropathies, ptosis, stool culture
myopathy unreactive pupils, dysphagia, Presence of toxin in the stool
constipation
Glycogen storage disease Hypotonia, weakness and contractures Creatine kinase usually
Pompe’s disease at birth elevated
Associated brain and eye problems Brain MRI for structural and
white matter abnormalities
Polyhydramnios with reduced fetal Muscle biopsy: merosin stain
movements Molecular DNA testing by
Inverted V-appearance of the mouth determining number of CTG
Examination of mother’s face shows inability repeats (normal range 5 - 39
to bury her eyelashes and grip myotonia repeats)
Premature cataract surgery in the mother EMG of the mother
Slender stature
Hypotonia with feeding problems at birth CK and EMG usually not
Weakness that is often non-progressive helpful
Nemaline myopathy: often associated with Muscle biopsy is critical for
feeding problems definitive diagnosis.
Central core: most often associated with ECG when nemaline and
malignant hyperthermia desmin myopathies are
Myotubular myopathy: Ptosis and suspected
extraocular palsies consistent The genetic basis for several
clinical features of the congenital myopathies
Enlarged heart in a very floppy weak has now been determined
newborn Blood smear vacuolated
Unexplained cardiac failure lymphocytes
Tongue may appear large Urine oligosaccharides
Typical ECG and ECHO
changes
Acid maltase assay in
cultured fibroblasts
Muscle biopsy usually not
necessary

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THE FLOPPY CHILD

ic disorder. Conditions that need to be VALUE AND CHOICE OF means that most neuromuscular condi-
excluded include trisomy 21, Prader- DIAGNOSTIC MODALITIES tions can now be diagnosed by molec-
Willi and Zellweger syndrome. At ular testing. Examples include spinal
birth the facial anomalies in Prader- Special investigations should be guid- muscular atrophy which can now be
Willi syndrome are often insignificant ed by clinical findings. Evaluation of confirmed by polymerase chain reac-
and the diagnosis is usually only tone and power should be delayed in tion (PCR) testing for a deletion of the
established after onset of obesity. the systemically unwell nutritionally survivor motor neuron (SMN) gene
Useful early markers include the pres- compromised child. Infective and bio- and congenital myotonic dystrophy
ence of feeding difficulties, small chemical parameters should first be which can be diagnosed by demon-
hands and feet, almond shaped eyes, normalised before attempts are made strating an expansion of cytosine
narrow bifrontal diameter and hypogo- to examine tone and power. thymine guanine (CTG) triplet repeats.
nadism (Fig. 7). Failure to identify Hypokalaemia and hypophospha-
electrophysiological abnormalities in a taemia in particular will cause DNA Xp21 deletion testing (PCR
neonate with profound hypotonia reversible weakness. Serum albumin, assays) can confirm the diagnosis in
should prompt testing for Prader-Willi calcium, phosphorus, alkaline phos- 65% of males with Duchenne muscular
syndrome. This can be done by a phatase and thyroxine levels will pro- dystrophy and 80% of males with
DNA methylation study which will vide confirmation of clinical suspicion Becker’s muscular dystrophy. Only in
detect 99% of cases. in malnutrition, ricketts and hypothy- the remaining cases is muscle biopsy
roidism. still advocated. Muscle enzymes levels
Fig. 7. A 1-year-old girl with Prader- (creatine kinase assay) are rarely help-
Willi syndrome. Marked hypotonia SUSPECTED CENTRAL CAUSE ful in the floppy infant, with the excep-
and feeding difficulties were evident tion of muscle disorders where crea-
during the first few months of her life. For infants with central hypotonia, ini- tine kinase values are elevated, such
tial investigations include karyotype as congenital muscular dystrophies
Zellweger syndrome presents in the and neuroimaging (CT or MRI scan). A and in some of the congenital structur-
newborn with typical facial dysmor- karyotype is a must in the dysmorphic al myopathies.
phism including high forehead, wide hypotonic child. This can be combined
patent fontanelles and sutures, shallow with FISH testing if Prader-Willi syn- Electromyography (EMG) should not
orbital ridges, epicanthus and microg- drome is suspected. Cranial MRI will be performed in isolation. It does not
nathia. Neurological manifestations identify patients with structural CNS allow for a definitive diagnosis as
are dominated by severe hypotonia malformations, neuronal migration there are virtually no waveforms that
with depressed or absent tendon defects and those with white matter are pathognomonic for specific dis-
reflexes, and poor sucking and swal- changes (congenital muscular dystro- ease entities. In the floppy child, EMG
lowing. Hepatomegaly and liver dys- phies in particular). Hypotonia may is indispensable in deciding whether
function are consistent findings. also be prominent in connective tissue there is true weakness due to neuro-
diseases such as Ehlers Danlos or muscular disease, or merely hypotonic-
Marfan’s syndrome. An excessive ity from causes in other systems or
range of joint mobility, unusual joint other parts of the nervous system. The
postures, the ability to do various con- abnormalities detected may then assist
tortions of the limbs and/or hyperelas- in localizing the disease process to the
ticity of the skin are important diag- neuron, neuromuscular junction or
nostic clues. Although metabolic disor- muscle. EMG is also useful to confirm
ders are well recognised as the cause a clinical suspicion of myotonia in the
for central hypotonia, because of the older child.
rarity of the conditions, the diagnostic
yield is low. Very long-chain fatty Nerve conduction studies are useful in
acids (VLCFA) testing should be per- the investigation of hereditary motor
formed if a peroxisomal disorder such sensory neuropathies and distinguish-
as Zellweger is suspected. ing axonal from demyelinating disor-
ders. Molecular DNA testing can then
SUSPECTED PERIPHERAL be used for specific demyelinating dis-
CAUSE orders. Commercial testing is not yet
available for most axonal forms of
Major discoveries have been made in hereditary neuropathies.
the genetic analysis of the muscular
dystrophies, spinal muscular atrophies Muscle biopsy remains the investiga-
and hereditary neuropathies. This tion of choice in an infant with a sus-

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The onset of the hypotonia mal tendon reflexes IN A NUTSHELL
is also important as it may • normal or mild motor retardation that
distinguish between When evaluating a floppy infant,
congenital and aquired improves later on the first goal should be to distin-
aetiologies. • normal muscle enzymes, EMG, guish whether the disorder is cen-
tral or peripheral in origin.
There are two approaches motor nerve conduction studies
to the diagnostic problem. (MNCS) and histology. Hypotonia with weakness suggests
The first is based on identi- a lower motor neuron lesion, where-
fying the neuro-anatomical PRINCIPLES OF as weakness is uncommon in disor-
site of the lesion or insult. MANAGEMENT ders affecting the upper motor neu-
The second is to determine ron except during the acute stage.
whether or not the hypoto- Regular physiotherapy will prevent con-
nia is accompanied by tractures. Occupational therapy is Evaluation of tone and power
weakness. important in facilitating activities of should be delayed in the unwell,
daily living. Vigorous treatment of respi- nutritionally compromised child.
Children with neuromuscu- ratory infections is indicated. Annual flu
lar disorders deserve spe- vaccination is necessary. Annual Muscle enzymes are rarely helpful
cial attention when it orthopaedic review is required to moni- in the floppy child, with the excep-
comes to anaesthesia. tor for scoliosis and to exclude hip dislo- tion of the congenital muscular dys-
cation/subluxation. trophies and some of the structural
pected congenital structural myopathy, Feeding intervention by nasogastric tube congenital myopathies.
as none of the clinical features are or gastrostomy will benefit the under-
truly pathognomonic. Even a CK with- nourished child. Maintenance of ideal EMG does not allow a definitive
in the reference range and normal weight is important, as excessive weight diagnosis but is indispensable in
EMG does not exclude the presence of gain will exacerbate existing weakness. deciding whether there is weakness
a myopathy. Muscle biopsy is also Children with neuromuscular disorders due to neuromuscular disease, or
indicated in infants with suspected deserve special attention when it comes merely hypotonia from causes in
limb-girdle muscular dystrophies to anaesthesia. The anaesthetist should other systems or parts of the nerv-
(LGMD). be forewarned about the possibility of ous system.
an underlying muscle disease even if the
The term ‘benign essential hypotonia’ child has very mild or non-existing The most common of the neuromus-
or ‘hypotonia with favourable outcome’ symptoms. A family history of muscle cular disorders, spinal muscular
should be used with caution since disease or mild hyper-CK-aemia may be atrophy (SMA), is now diagnosable
newer investigative techniques have of importance. Muscle relaxants should by molecular genetic analysis
resulted in most previously labelled only be used if essential because of (PCR).
cases being classified into specific disor- their more profound and prolonged
ders. There are however many benign effect in myopathic children. All children Where clinical evaluation suggests
congenital hypotonia cases that remain with complex multisystem involvement
unclassified, even with detailed exami- neuromuscular disease should also be (i.e. hypotonia plus) inborn errors
nation of the muscles. Patients labelled considered potentially susceptible to of metabolism should be excluded.
as ‘hypotonia with favourable outcome’ malignant hypothermia (the strongest
should fulfil all of the following criteria1: correlation is with central core disease) Children with neuromuscular disor-
and implicating agents should therefore ders deserve special attention when
• early hypotonia, usually since birth be avoided. it comes to anaesthesia.
• active movements of limbs and nor-
Ethical considerations such as the The term ‘benign essential hypoto-
appropriateness of cardiopulmonary nia’ or ‘hypotonia with a
resuscitation in the event of cardiac favourable outcome’ should be used
arrest or acute respiratory failure need with caution and only after compli-
to be addressed sensitively. ance with strict diagnostic criteria.

References available on request.

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