SYMPOSIUM: NEUROLOGY
Evaluation of the floppy
infant
Rakesh Kumar Jain
Sandeep Jayawant
Abstract
This review outlines a clinical approach to the evaluation of the floppy
infant. Attention is drawn to the varied manner in which the condition
can present, and emphasis is placed upon a detailed assessment of char-
acteristic clinical findings. A distinction is drawn between central and
peripheral causes for hypotonia. Guidance is given regarding the impor-
tance of evaluating the child for signs of weakness, which is an important
marker of neuromuscular pathology. Reference is made to situations
where peripheral pathology may mimic central disorders. A diagnostic
algorithm is outlined for the investigation of neuromuscular disorders,
and reference is made to the discrepancy in findings that often exists
between electromyography and muscle biopsy findings. Attention is
drawn to available newer diagnostic and therapeutic options, as well as
the importance of addressing ethical issues, which become of particular
importance once a diagnosis is reached. In practice points, the emphasis
has been given to first line investigations based on clinical clues.
Keywords hypotonia; neuromuscular; neuropathy
Introduction and definition
The word ‘floppy’ can be used to mean:

decrease in muscle tone (hypotonia);

decrease in muscle power (weakness);

ligamentous laxity and increased range of joint mobility.
Strictly speaking, the term ‘floppy’ should be used to describe
hypotonia. The interconnection between tone, muscle strength
and joint mobility can be appreciated through a consideration of
the definition of tone e the resistance to passive movement
around a joint. Phasic tone is assessed by the response of the
muscle to a rapid stretch, illustrated classically by a tendon
reflex, whilst postural tone is measured by the response of the
muscle to a sustained low-intensity stretch, as illustrated by the
body’s ability to maintain posture against the force of gravity.
Clinical appearance
Some features are common to all floppy infants regardless of the
aetiology and location of the abnormality. A child is generally
Rakesh Kumar Jain MBBS MRCPCH DCH is Consultant, Level 2, at the
Children’s Hospital, John Radcliffe Hospital, Headington, Oxford, UK.
Sandeep Jayawant MD MB DCH MRCP(UK) FRCPCH is Consultant Paediatric
Neurologist in the Dept. of Paediatric Neurology at the John Radcliffe
Hospital, Headley Way, Headington, Oxford, UK.
PAEDIATRICS AND CHILD HEALTH 21:11
What’s new?
C Recently, array CGH (Comparative Genomic Hybridization) has
come up as a powerful diagnostic tool having detection rate of
5e17% in cases of normal karyotype.
C Exon sequencing is promising in detecting causal genetic
variants of rare monogenic disorders.
C Newborn screening using tandem mass spectrometry can be
helpful for metabolic disorders.
C Recent advances in genetics have uncovered new conditions
causing hypotonia and weakness such as congenital myas-
thenic syndromes and spinal muscular atrophy variants.
C Some of these advances have allowed for specific therapeutic
interventions, e.g. use of acetylcholinesterase inhibitors,
3,4-diaminopyridine and ephedrine,salbutamol or fluoxetine in
some congenital myasthenic syndromes.
C Antisense oligonucleotide therapy has been under trial for
Duchenne muscular dystrophy.
C Enzyme replacement therapy (myozyme) for infantile Pompe
disease.
said to be floppy if he/she assumes a frog-like posture, is unable
to maintain normal posture against gravity, exhibits diminished
resistance to passive movements and has an excessive range of
joint mobility. Table 1 lists some of the clinical signs with which
a floppy infant may present; these features may or may not
coexist in the same infant.
Common modes of presentation
The clinical consequences of hypotonia and/or weakness may be
evident even in antenatal life. Specific questions in the history
should address whether fetal movements were normal, as well as
whether there was evidence of polyhydramnios .In the neonatal
period, the manner of presentation depends on the severity of the
condition. This ranges from the consequences of fetal immobi-
lization, such as hip dislocation, arthrogryposis, talipes and
flexion deformity of all limbs, to respiratory and feeding
Clinical signs in a floppy infant
C Observation of a ‘frog-leg’ posture. This generally implies
reduced spontaneous movement, with the legs fully abducted
and arms lying beside the body either extended or flexed
C Significant head lag on traction or pull-to-sit manoeuvre and
excessively rounded back when sitting (>33 weeks)
C Rag-doll posture on ventral suspension
C Vertical suspension test e feeling of ‘slipping through the
hands’ when the infant is held under the arms
C Various associated examination findings such as flat occiput or
congenital dislocation of the hips, arthrogryposis, paradoxical
breathing
Table 1
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 SYMPOSIUM: NEUROLOGY
Figure 1 Head lag.
difficulties (slow feeding, recurrent choking or aspiration
episodes). Later in infancy, hypotonia may be more obvious once
delayed achievement of motor milestones becomes evident, with
or without accompanying delay in other areas of development.
Clinical confirmation of hypotonia
Once the suspicion of hypotonia has been raised, the evaluation
of the floppy infant should proceed by searching for those clinical
signs that corroborate the diagnosis (Figures 1 and 2).
Figure 2 Classic posture in hypotonia.
PAEDIATRICS AND CHILD HEALTH 21:11
Clinical features suggestive of hypotonia of central
origin
C Social and cognitive impairment in addition to motor delay
C Dysmorphic features implying a syndrome or other organ mal-
formations sometimes implying a syndrome
C Fisting of hands
C Normal or brisk tendon reflexes
C Features of pseudobulbar palsy, brisk jaw jerk, crossed adductor
response or scissoring on vertical suspension
C Features that may suggest an underlying spinal dysraphism
C History suggestive of hypoxic-ischaemic encephalopathy, birth
trauma or symptomatic hypoglycaemia
C Seizures
Table 2
Important diagnostic clues on examination

Skin pallor, bruising, petechiae, or evidence of trauma e
traumatic myelopathy

Abnormalities of respiratory rate, pattern, or diaphragmatic
movement e congenital myopathies

Cardiomyopathy e consider carnitine deficiency, fatty acid
oxidation disorders ,acid maltase deficiency, Pompe’s disease

Hepatosplenomegaly e storage disorders or congenital
infections

Renal cysts, liver dysfunctions, high forehead and wide
fontanelles e Zellweger’s spectrum disorder

Congenital cataracts, glaucoma e Oculocerebrorenal (Lowe)
syndrome

Abnormal urine odour e metabolic disorders

Hypopigmentation, undescended testes e PradereWilli
syndrome

Abnormal fad pad and inverted nipples e congenital disor-
ders of glycosylation (CDG).
Indicators of peripheral hypotonia
C Delay in motor milestones with relative normality of social and
cognitive development
C Family history of neuromuscular disorders/maternal myotonia
C Reduced or absent spontaneous antigravity movements,
reduced or absent deep tendon jerks and increased range of
joint mobility
C Frog-leg posture or ‘jug-handle’ posture of arms in association
with marked paucity of spontaneous movement
C Myopathic facies (open mouth with tented upper lip, poor lip
seal when sucking, lack of facial expression, ptosis and
restricted ocular movements)
C Muscle fasciculation (rarely seen but of diagnostic importance
when recognized)
C Other corroborative evidence including muscle atrophy, muscle
hypertrophy and absent or depressed deep tendon reflexes
Table 3
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 SYMPOSIUM: NEUROLOGY
Conditions where central and peripheral hypotonia may
coexist
C Familial dysautonomia
C Hypoxic-ischaemic encephalopathy
C Infantile neuroaxonal degeneration
C Lipid storage diseases
C Lysosomal disorders
C Mitochondrial disorders
C Perinatal asphyxia secondary to motor unit disease
Table 4
Diagnostic approach
The initial approach to a floppy infant is to determine whether
the problem is of central or peripheral origin (Tables 7a & 7b).
Paralytic hypotonia with significant weakness suggests a periph-
eral neuromuscular problem, whereas non-paralytic hypotonia
without significant weakness points to a central cause which may
be neurological, genetic, syndromic or metabolic.
Central hypotonia contributes 60e80% of all hypotonic
infants and is suggested by clinical features as described in
Table 2. The presence of these findings does not, however,
exclude a peripheral aetiology of weakness. In some cases
features suggesting both central and peripheral aetiologies may
be seen.
Table 3 shows features in the history and clinical examination
that indicate the hypotonia and/or weakness are more likely due
Conditions associated with central (non-paralytic)
hypotonia
Acute encephalopathies
C Birth trauma
C Hypoxic-ischaemic encephalopathy
C Hypoglycaemia
Chronic encephalopathies
C Cerebral malformations
C Hypotonic cerebral palsy
C Inborn errors of metabolism (mucopolysaccharidoses, amino-
acidurias, organic acidurias, lipidoses, glycogen storage
diseases, mitochondrial diseases and Menkes syndrome)
C Chromosomal disorders (Prader-Willi syndrome, trisomy 21)
C Genetic disorders (familial dysautonomia, Lowe syndrome)
C Peroxisomal disorders (neonatal adrenoleukodystrophy,
Zellweger syndrome)
C Endocrine/Nutritional(hypothyroidism, rickets, renal tubular
acidosis)
Connective tissue disorders
C Ehlers-Danlos syndrome
C Osteogenesis imperfecta
C Congenital ligamentous laxity
C Benign congenital hypotonia
Table 5
PAEDIATRICS AND CHILD HEALTH 21:11
to peripheral (neuromuscular) causes. During infancy, formal
testing for both tone and weakness is more difficult and relies
more heavily on clinical evaluation as well as the search for
corroborating risk factors.
The preservation of muscle power with hypotonia and
hyperreflexia indicates central origin for floppiness. The relative
preservation of alertness, significant weakness, lack of anti-
gravity movement and absent deep tendon reflexes suggest lower
motor neuron type lesion. However, the lesion of neuromuscular
junction may be associated with preserved reflexes. In some
conditions, both central and peripheral hypotonia may coexist
(Table 4).
Once the decision about central or peripheral (neuromus-
cular) aetiology has been made, investigations are directed
accordingly to identify the specific condition causing the hypo-
tonia. Tables 5 and 6 list some of the causes of hypotonia and/or
weakness resulting from central and peripheral (neuromuscular)
causes, respectively. Table 7a & 7b shows comparative diag-
nostic features of hypotonia according to different sites of
involvement.
Investigations where central hypotonia is suspected
The range of investigations that may yield diagnostic clues in the
clinical setting of non-paralytic/central hypotonia are listed in
Table 8. The diagnosis of central hypotonia attributable to
hypoxic-ischaemic encephalopathy is based upon an appropriate
clinical history along with concordant imaging studies of the
Causes of paralytic/neuromuscular hypotonia
Spinal muscular atrophy
SMA Type 1 e Werdnig-Hoffmann disease
Chronic SMA e Type 2 & 3
SMARD 1
Paralytic poliomyelitis
Neuropathies
C Hereditary motor-sensory neuropathy
C Congenital hypomyelinating neuropathy
C Acute demyelinating polyneuropathy
Neuromuscular junction problems
C Botulism
C Transient neonatal myasthenia
C Autoimmune myasthenia
C Congenital myasthenic syndromes
Muscular disorders
C Congenital myopathies (nemaline rod myopathy, myotubular
myopathies, central core disease, minicore disease, Bethlem
and Ullrich myopathies)
C Congenital muscular dystrophies (CMD) (Walker-Warburg,
Fukuyama, muscle-eye-brain disease, merosin-positive CMD, etc)
C Congenital myotonic dystrophy
C Metabolic myopathies (acid maltase deficiency, phosphorylase
deficiency, mitochondrial myopathy
C Endocrine myopathies (hypothyroidism)
Table 6
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 SYMPOSIUM: NEUROLOGY

Differentiating features of a floppy infant according to site of involvement

Site of involvement Extent of weakness Proximal vs. distal
Face Arms Legs weakness

Central e þ þ > or ¼
Anterior horn cell  þþþþ þþþþ > or ¼
Peripheral nerve e þþþ þþþ <
Neuromuscular junction þþþ þþþ þþþ ¼
Muscle Variable þþ þ >

Table 7a

Differentiating features of a floppy infant according to site of involvement

Site of involvement Deep tendon reflexes EMG Muscle biopsy

Central Normal or increased Normal Normal

Anterior horn cell Absent Fasciculation/fibrillation Denervation pattern
Peripheral nerve Decreased Decreased nerve conduction velocity N/A
Neuromuscular junction Normal Decremental/incremental Normal
Muscle Decreased Short duration small amplitude potential Characteristic

Table 7b

brain. Metabolic disorders are rare and despite extensive inves-
tigations the diagnostic yield may be quite low.
Investigations where peripheral hypotonia is suspected
Investigations likely to yield diagnostic clues in cases where
paralytic/neuromuscular hypotonia is suspected are listed in
Table 9.
Myotonic dystrophy is usually suspected on the basis of
known family history or recognition of the disorder in an affected
Investigations in cases where a central cause for
hypotonia is suspected
C Serum electrolytes, including calcium and phosphate, serum
alkaline phosphatase, venous blood gas, thyroid function tests
C Plasma copper/caeruloplasmin assay (as screening test for
Menkes syndrome)
C Chromosomal analysis (trisomy), testing for PradereWilli
syndrome(15q11e13)
C Plasma amino acids and urine organic acids
C Urine mucopolysaccharide screen (GAG)
C Molecular/biochemical diagnosis of pro-collagen disorders
C Very long chain fatty acids
C Medical genetics opinion
C Ophthalmology opinion
C Brain imaging (CT/MRI)
Table 8
mother, and can be confirmed by testing for the expanded CTG
trinucleotide repeat sequence on chromosome 19q13.2eq13.3. In
the absence of a diagnosis of myotonic dystrophy, we support the
early use of electromyography (EMG)/nerve conduction studies
(NCS) when a peripheral cause is likely. Areflexia, decreased
limb movements, generalized weakness sparing the face, normal
creatinine kinase and denervation on EMG should prompt
investigation for anterior horn cell disorders (spinal muscular
atrophy), and can be confirmed by testing for the homozygous
deletion of exon 7 in the telomeric survival motor neurone gene.
Failure to identify electrophysiological abnormalities should
prompt testing for PradereWilli syndrome, which can be
confirmed by FISH testing for deletion on chromosome 15q13
and if negative by MLPA (Multiplex Ligation-dependent Probe
Amplification) testing.
Arthrogryposis, feeding difficulties, recurrent apnoeic/
choking episodes, ophthalmoplegia, ptosis and fatigability
should prompt investigation for congenital myasthenic
syndromes. Congenital myasthenic syndrome (CMS) can be
associated with arthrogryposis multiplex congenital (AMC).
Repetitive nerve stimulation shows an electrodeceremental
response of >10% in the amplitude of compound muscle
action potential suggesting neuromuscular blockage. However,
an abnormal ‘jitter’ on stimulated single fiber EMG is the most
sensitive indicator of a block in neuromuscular transmission.
In addition to above EMG findings, AchR and MuSK antibodies
are negative in congenital myasthenia syndrome. Depending
on the phenotype mutations in the CMS genes can be tested
for.
Finally, muscle biopsy is recommended in neonates with
weakness, even if needle EMG is normal (Figure 3). Care should,

PAEDIATRICS AND CHILD HEALTH 21:11 498 Ó 2011 Elsevier Ltd. All rights reserved.
 SYMPOSIUM: NEUROLOGY
Investigations of peripheral hypotonia
C Creatinine kinase
C Lactate
C EMG /NCS/repetitive nerve stimulation test
C Muscle biopsy (histology, immunohistochemistry, electron
microscopy, respiratory chain enzyme analysis)
C Genetic testing (SMN gene deletion present in 95% of cases of
spinal muscular atrophy type 1, myotonic dystrophy, congenital
myasthenic syndromes)
C Nerve biopsy (rarely)
C Tensilon test
Table 9
however, be taken in patient selection for muscle biopsy because
of an increased risk of anaesthetic complications (postoperative
respiratory failure and reactions to anaesthetic agents, particu-
larly malignant hyperthermia and rhabdomyolysis).
EMG studies are used as a supportive diagnostic tool in
deciding whether there is true weakness due to neuromuscular
disease, or hypotonia from causes in other systems or other parts
of the nervous system, and whether the process is due to
a myopathic, neuropathic or a denervating process. In general,
EMG can be performed at any age, although some caution is
required in the interpretation of results within the first 6e8
weeks of life, particularly if the baby was premature. Whilst
severe myopathy or neuropathy is not usually difficult to diag-
nose on EMG, studies on cases of mild weakness are usually
inconclusive. In general, EMG and biopsy studies more often
concur in denervation than myopathy. Classic EMG/NCS find-
ings in myopathic and neurogenic disorders are outlined in Table
10. Recent advances in the diagnosis of congenital myasthenic
syndromes allow for DNA testing in some of the common
syndromes where there is strong clinical suspicion, particularly
in young children where accurate neurophysiology evidence is
sometimes difficult to obtain.
Left, muscle biopsy (histochemistry) in core myopathy and right, electron microscopy in nemaline rod myopathy (congenital myopathy).
Figure 3
PAEDIATRICS AND CHILD HEALTH 21:11
Useful EMG features in peripheral hypotonia
C EMG /NCS studies may distinguish between neurogenic,
myopathic and myasthenic aetiologies for hypotonia
C Neurogenic e large amplitude action potentials, reduced inter-
ference pattern, increased internal instability
C Myopathic e small amplitude action potentials with increased
interference pattern
C Myotonic e increased insertional activity
C Myasthenic e abnormal repetitive stimulation and single fiber
EMG studies (abnormal jitter)
Table 10
Therapeutic approach
Various aspects of function may be affected in a floppy infant. In
most cases, supportive therapies are indicated. Few conditions
have specific treatments. These include hypothyroidism
(thyroxine), some types of congenital myasthenic syndromes
(pyridostigmine or neostigmine) and rickets (vitamin D). Some
metabolic disorders may respond to specific dietary modifica-
tions or enzyme replacement therapies. The mainstays of treat-
ment are outlined in Table 11.
Prognosis and prevention
Rapid as well as accurate diagnosis of individual cases is vital in
order to provide precise prognostic information. Clinical
involvement of bulbar and chest muscles often determines the
survival. The majority of hypotonic infants improve their tone
but may remain developmentally delayed. In infants who are
profoundly weak the risk of death is greatest under the age of 2
years. Ethical considerations, such as the appropriateness of
cardiopulmonary resuscitation in the event of cardiac arrest or
acute respiratory failure, need to be addressed sensitively.
Informed discussion around these issues requires detailed
knowledge, where available, of specific conditions and, in
particular, their presentation, clinical features, course and
499 Ó 2011 Elsevier Ltd. All rights reserved.
 SYMPOSIUM: NEUROLOGY
Principles of management
C Physiotherapy e stretches aimed at prevention of contractures
C Occupational therapy - appliances, improvement of posture and
function, facilitating activities of daily living
C Prevention and correction of scoliosis
C Evaluation and treatment of associated cardiac dysfunction
C Respiratory support - assessment of requirement for invasive or
non-invasive ventilation and/or tracheostomy
C Feeding - nasogastric feeding, caloric supplementation,
gastrostomy
C Management of gastro-oesophageal reflux - medical or
fundoplication
C Orthopaedic intervention in setting of established or evolving
joint contractures
C Encouragement of overall development and stimulation of
learning
C Prevention (influenza and pneumococcal vaccination) and
prompt treatment of respiratory infections
Table 11
outcomes. Prenatal diagnosis using amniocentesis or chorionic
villus sampling is often feasible if a definitive diagnosis has been
reached in the index case. A C
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Practice points
C Central causes of hypotonia must be distinguished from those
due to neuromuscular disease, once established, MRI and/ or
EEG should be the first line investigations.
C Presence of dysmorphic features should prompt karyotype
analysis or other specific metabolic or genetic tests.
Suspected peripheral hypotonia should be investigated by
DNA based tests for common disorders depending on relevant
clues (SMA, MD, PWS, etc.) before electrophysiological studies
or muscle biopsy.
C Hypotonia with weak antigravity movements is the most
sensitive marker for neuromuscular disorders.
C Genetic-metabolic disorders contribute to more than 50%
cases of hypotonia.
C A combination of a good history, clinical examination, neuro-
imaging and focused genetic tests can diagnose up to 60% of
hypotonic infants.
C Depending upon various clues, genetic tests could be done as
a first line investigation.
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