1. 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
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-
or oligohydramnios. The incidence of breech presentation is higher in fetuses
with neuromuscular disorders as turning requires adequate fetal mobility.
Documentation of birth trauma, birth anoxia, delivery complications, low cord
R van Toorn pH and Apgar scores are crucial as hypoxic-ischaemic encephalopathy remains
MB ChB, (Stell) MRCP (Lond), FCP (SA) an important cause of neonatal hypotonia. Neonatal seizures and an encephalo-
Specialist
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
Department of Paediatrics and Child Health
aquired aetiologies. Enquire about consanguinity and identify other affected fam-
Faculty of Health Sciences
ily members in order to reach a definitive diagnosis, using a detailed family
Stellenbosch University and pedigree to assist future genetic counselling.
Tygerberg Children’s Hospital
CLINICAL CLUES ON NEUROLOGICAL EXAMINATION
Ronald van Toorn obtained his medical
degree from the University of Stellenbosch, There are two approaches to the diagnostic problem. The first is based on identi-
and completed his paediatric specialist fying the neuro-anatomical site of the lesion or insult. The second is to determine
whether or not the hypotonia is accompanied by weakness. Careful neurological
training at both Red Cross Children’s
examination should, in most cases, localise the site of the lesion to the upper
Hospital in Cape Town and the Royal
motor neuron (UMN) or lower motor neuron (LMN) unit. Useful clues are listed in
College of Paediatricians in London. One Fig. 1.
of his interests is in the field of neuromus-
cular medicine. His working experience Next assess whether the hypotonia is accompanied by weakness. Weakness is
includes the neuromuscular clinics attached uncommon in UMN hypotonia except in the acute stages. Hypotonia with pro-
found weakness therefore suggests involvement of the LMN. Assessment of muscle
to Birmingham Children’s, Red Cross
power of infants is generally limited to inspection.
Children’s, Guy’s and St Thomas’ hospitals.
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.
August 2004 Vol.22 No.8 CME 449

2. THE FLOPPY CHILD
Floppy weak
Hypo- to areflexia
Floppy strong Selective motor delay
Normal head circumference
Increased tendon reflexes and growth
Extensor plantar response Preserved social interaction
Sustained ankle clonus Weakness of antigravitational
Global developmental delay limb muscles
Microcephaly or suboptimal Low pitched weak cry
head growth Tongue fasciculations
Obtundation convulsions Paradoxical chest wall
Axial weakness a significant movement
feature
Upper motor neuron Lower motor neuron
disorder disorder
Central hypotonia 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
Hypoxic ischaemic Spinal muscuar Congenital
Triosomy 21 dystrophy structural
encephalopathy
Prader-Willi syndrome Congenital myotonic myopathies
Cerabral malformations
Zellweger syndrome 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
450 CME August 2004 Vol.22 No.8

3. THE FLOPPY CHILD
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-
roanatomical localisation according to
Fig. 2.1. A 12-week-old male infant with the compartments of the LMN. The
excessive headlag evident on ‘pull-to-sit’. compartments and disease associa-
Note the hypotonic posture of the legs tions are listed in Fig. 3.
with external rotation.
Examine the tongue for size and fasci-
culations. Fasciculations, irregular
twitching movements, generally indi-
cate an abnormality of the anterior
horn cells (Fig. 4). Do not examine the
tongue while the infant is crying. The
co-existence of atrophy would strongly
favour a denervative aetiology. An
ECG may be helpful in demonstrating
baseline fasciculations of the inter-
costal muscles (Fig 5). Enlargement of
Fig. 2.2. The same infant in horizontal
the tongue may suggest a storage dis-
suspension. Note the inverted U posture.
order such as Pompe’s disease.
A distinct pattern of weakness may Fig. 6. Ptosis and external ophthalmo-
favour certain aetiologies: plegia in a floppy weak child sugges-
• Axial weakness is a significant fea- tive of myasthenia gravis.
ture in central hypotonia.
• Generalised weakness with sparing
of the diaphragm, facial muscles, Where clinical evaluation suggests
pelvis and sphincters suggests ante- complex multisystem involvement (i.e.
rior horn cell involvement. hypotonia plus) inborn errors of
• With myasthenic syndromes, the metabolism should be excluded.
bulbar and oculomotor muscles Referral to a tertiary centre for meta-
exhibit a greater degree of involve- bolic investigations would then be
ment. indicated.
• Progressive proximal symmetrical
Fig. 4. Tongue fasciculations in a child
weakness suggests a dystro-
with spinal muscular atrophy. The com- THE FLOPPY STRONG CHILD
phinopathy. Signs of proximal
bination of fasciculations with atrophy
weakness in the older infant The presence of facial dysmorphism
is strongly indicative of muscle dener-
include a lordotic posture, should alert the doctor to the possibili-
vation.
Trendelenburg gait and Gower ty of an underlying syndrome or genet-
sign.
• A striking distribution of weakness
of the face, upper arms and shoul-
ders suggests fascioscapulohumeral
muscular dystrophy.
• Distal muscle groups are predomi-
nantly affected with peripheral neu-
ropathies. Signs suggesting distal
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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4. THE FLOPPY CHILD
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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5. THE FLOPPY CHILD
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
of spinal dysraphism Mixed deep tendon reflexes with absent
abdominal and anal reflexes
Spinal muscular atrophy Tongue atrophy and fasciculations ECG: Baseline fasciculations
Paradoxical breathing pattern Deletion of the survival motor
Severe proximal muscle weakness with neuron (SMN) gene by PCR
absent tendon reflexes testing
Preserved social interaction
Peripheral neuropathy Weakness predominantly distal Motor nerve conduction
In most cases absent deep tendon reflexes studies
Pes cavus Sural nerve biopsy
Molecular DNA testing is
available for specific
demyelinating disorders
Myasthenia gravis Greater involvement of oculomotor and Response to acethylcholine
bulbar muscles esterase inhibitors
True congenital myasthenia due to receptor Single-fibre EMG
defects is rare Serum antibodies to
Exclude transient neonatal form from acethylcholine receptors
maternal history Electrodiagnostic studies not
universally positive in young
patients
Infantile botulism Acute onset descending weakness, Isolation of organism from
cranial neuropathies, ptosis, stool culture
unreactive pupils, dysphagia, Presence of toxin in the stool
constipation
Congenital muscular Hypotonia, weakness and contractures Creatine kinase usually
dystrophy at birth elevated
Associated brain and eye problems Brain MRI for structural and
white matter abnormalities
Muscle biopsy: merosin stain
Congenital myotonic Polyhydramnios with reduced fetal Molecular DNA testing by
dystrophy movements determining number of CTG
Inverted V-appearance of the mouth repeats (normal range 5 - 39
Examination of mother’s face shows inability repeats)
to bury her eyelashes and grip myotonia EMG of the mother
Premature cataract surgery in the mother
Congenital structural Slender stature CK and EMG usually not
myopathy Hypotonia with feeding problems at birth helpful
Weakness that is often non-progressive Muscle biopsy is critical for
Nemaline myopathy: often associated with definitive diagnosis.
feeding problems ECG when nemaline and
Central core: most often associated with desmin myopathies are
malignant hyperthermia suspected
Myotubular myopathy: Ptosis and The genetic basis for several
extraocular palsies consistent of the congenital myopathies
clinical features has now been determined
Glycogen storage disease Enlarged heart in a very floppy weak Blood smear vacuolated
Pompe’s disease newborn lymphocytes
Unexplained cardiac failure Urine oligosaccharides
Tongue may appear large Typical ECG and ECHO
changes
Acid maltase assay in
cultured fibroblasts
Muscle biopsy usually not
necessary
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6. 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
(creatine kinase assay) are rarely help-
ful in the floppy infant, with the excep-
SUSPECTED CENTRAL CAUSE
tion of muscle disorders where crea-
For infants with central hypotonia, ini- tine kinase values are elevated, such
tial investigations include karyotype as congenital muscular dystrophies
and neuroimaging (CT or MRI scan). A and in some of the congenital structur-
karyotype is a must in the dysmorphic al myopathies.
hypotonic child. This can be combined
with FISH testing if Prader-Willi syn- Electromyography (EMG) should not
drome is suspected. Cranial MRI will be performed in isolation. It does not
identify patients with structural CNS allow for a definitive diagnosis as
malformations, neuronal migration there are virtually no waveforms that
defects and those with white matter are pathognomonic for specific dis-
changes (congenital muscular dystro- ease entities. In the floppy child, EMG
phies in particular). Hypotonia may is indispensable in deciding whether
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
Fig. 7. A 1-year-old girl with Prader-
ticity of the skin are important diag- neuron, neuromuscular junction or
Willi syndrome. Marked hypotonia
nostic clues. Although metabolic disor- muscle. EMG is also useful to confirm
and feeding difficulties were evident
ders are well recognised as the cause a clinical suspicion of myotonia in the
during the first few months of her life.
for central hypotonia, because of the older child.
rarity of the conditions, the diagnostic
Zellweger syndrome presents in the yield is low. Very long-chain fatty Nerve conduction studies are useful in
newborn with typical facial dysmor- acids (VLCFA) testing should be per- the investigation of hereditary motor
phism including high forehead, wide formed if a peroxisomal disorder such sensory neuropathies and distinguish-
patent fontanelles and sutures, shallow as Zellweger is suspected. ing axonal from demyelinating disor-
orbital ridges, epicanthus and microg- ders. Molecular DNA testing can then
nathia. Neurological manifestations be used for specific demyelinating dis-
are dominated by severe hypotonia SUSPECTED PERIPHERAL orders. Commercial testing is not yet
with depressed or absent tendon CAUSE available for most axonal forms of
reflexes, and poor sucking and swal- hereditary neuropathies.
Major discoveries have been made in
lowing. Hepatomegaly and liver dys-
the genetic analysis of the muscular
function are consistent findings. Muscle biopsy remains the investiga-
dystrophies, spinal muscular atrophies
tion of choice in an infant with a sus-
and hereditary neuropathies. This
454 CME August 2004 Vol.22 No.8

7. THE FLOPPY CHILD
The onset of the hypotonia mal tendon reflexes
• normal or mild motor retardation that
IN A NUTSHELL
is also important as it may
improves later on
distinguish between When evaluating a floppy infant,
• normal muscle enzymes, EMG, the first goal should be to distin-
congenital and aquired
motor nerve conduction studies guish whether the disorder is cen-
aetiologies. (MNCS) and histology. tral or peripheral in origin.
PRINCIPLES OF Hypotonia with weakness suggests
There are two approaches MANAGEMENT a lower motor neuron lesion, where-
to the diagnostic problem. as weakness is uncommon in disor-
Regular physiotherapy will prevent con-
The first is based on identi- ders affecting the upper motor neu-
tractures. Occupational therapy is
fying the neuro-anatomical ron except during the acute stage.
important in facilitating activities of
site of the lesion or insult. daily living. Vigorous treatment of respi- Evaluation of tone and power
The second is to determine ratory infections is indicated. Annual flu should be delayed in the unwell,
whether or not the hypoto- vaccination is necessary. Annual nutritionally compromised child.
nia is accompanied by orthopaedic review is required to moni- Muscle enzymes are rarely helpful
tor for scoliosis and to exclude hip dislo-
weakness. in the floppy child, with the excep-
cation/subluxation. tion of the congenital muscular dys-
Feeding intervention by nasogastric tube trophies and some of the structural
Children with neuromuscu- or gastrostomy will benefit the under- congenital myopathies.
nourished child. Maintenance of ideal
lar disorders deserve spe- EMG does not allow a definitive
weight is important, as excessive weight
cial attention when it gain will exacerbate existing weakness. diagnosis but is indispensable in
comes to anaesthesia. Children with neuromuscular disorders deciding whether there is weakness
deserve special attention when it comes due to neuromuscular disease, or
pected congenital structural myopathy, to anaesthesia. The anaesthetist should merely hypotonia from causes in
as none of the clinical features are be forewarned about the possibility of other systems or parts of the nerv-
truly pathognomonic. Even a CK with- an underlying muscle disease even if the ous system.
in the reference range and normal child has very mild or non-existing The most common of the neuromus-
EMG does not exclude the presence of symptoms. A family history of muscle cular disorders, spinal muscular
a myopathy. Muscle biopsy is also disease or mild hyper-CK-aemia may be atrophy (SMA), is now diagnosable
indicated in infants with suspected of importance. Muscle relaxants should by molecular genetic analysis
limb-girdle muscular dystrophies only be used if essential because of (PCR).
(LGMD). their more profound and prolonged
effect in myopathic children. All children Where clinical evaluation suggests
with complex multisystem involvement
The term ‘benign essential hypotonia’
neuromuscular disease should also be (i.e. hypotonia plus) inborn errors
or ‘hypotonia with favourable outcome’
considered potentially susceptible to of metabolism should be excluded.
should be used with caution since
newer investigative techniques have malignant hypothermia (the strongest Children with neuromuscular disor-
resulted in most previously labelled correlation is with central core disease) ders deserve special attention when
cases being classified into specific disor- and implicating agents should therefore it comes to anaesthesia.
ders. There are however many benign be avoided.
The term ‘benign essential hypoto-
congenital hypotonia cases that remain
Ethical considerations such as the nia’ or ‘hypotonia with a
unclassified, even with detailed exami-
appropriateness of cardiopulmonary favourable outcome’ should be used
nation of the muscles. Patients labelled
resuscitation in the event of cardiac with caution and only after compli-
as ‘hypotonia with favourable outcome’
arrest or acute respiratory failure need ance with strict diagnostic criteria.
should fulfil all of the following criteria1:
to be addressed sensitively.
• early hypotonia, usually since birth
References available on request.
• active movements of limbs and nor-
August 2004 Vol.22 No.8 CME 455