Approach to hypotonia

Done by : Atheer Altamimi ,Bashayer Alkhalifah , Khawlah Alhaqbani

Under supervision of : Dr. Omaima Alzaher
Learning Objectives.

01. 02. 03.

Definitions Approach Central hypotonia
Tone, hypotonia, power, History and examination Clinical features, diagnostic
weakness Studies treatment

04. 05.
Peripheral hypotonia Case discussion
Clinical features, diagnostic
Studies treatment
 Definitions.
Tone : resistance (tension) in the muscle to passive movement.

Hypotonia is reduced resistance to passive range of motion around

the joints . caused by disorders that affect any level of the
nervous system brain, brain stem, spinal cord, peripheral
nerves, neuromuscular junction and muscle.

Muscle power : the ability to generate maximal Active

contractile force against resistance in the fastest possible time

weakness is reduction in the maximum power that can be generated

actively .
History.
Most common chief complaint
- Developmental delay
- Floppy infant

HPI
onset, course, duration , any associated symptoms

Prenatal History: TORCH infections? Drugs or alcohol? Maternal

illness? Fetal movements?

Neonatal History: Delivery complications? Preterm delivery?

Seizures?
History.
Past Medical History:
Admission with respiratory problems? Constipation? Snoring?
Sleeping disturbance?
Developmental History: Delayed milestone attainment? Loss of
milestones? Motor, social and language incongruence?
( Motor delay with normal social and language development
decrease the likelihood of brain pathology )

Feeding History: Stamina with feeding? Choking or aspiration?

Honey or corn syrup?

Family History: Other children? Consanguinity? Developmental

delay? Neurological disease? Premature death? Metabolic or
genetic diseases?
Physical examination.
General Physical Examination:
Position of the child (frog-leg position) , Alertness , Quality of the cry ,
Dysmorphic features, Ptosis, Facial expression.
Systems: Cardiovascular findings, organomegaly, umbilical hernia, small
genitalia, skin
Neurological Examination: Localize the lesion.
Cranial nerves: Extraocular movements? Muscles of facial expression?
Fasciculations of tongue?
Tone: Posture? Horizontal and vertical suspension? Scissoring or spasticity?
axial versus appendicular tone
In assessing tone the child should be alert but not crying*
Strength: Proximal versus distal weakness? Symmetry?
Reflexes: Hyperactive? Symmetry? Readily elicited? Clonus?
Muscles: Atrophy? Symmetry? hypertrophy
180° flip manoeuvre

1- observe in supine position

2- Pul to set
pulling the wrist or shoulder to sitting position , hypotonic
infants will be unable to control their heads ( head lag ) + UL
resistance
- setting position (still rounded, so the baby slumps
forward )
3- Vertical suspension
healthy infant should maintain the head upright and mid- line
without slipping through the examiner’s hands
180° flip manoeuvre

4- Horizontal suspension
infant should maintain a straight back with the head upright and
limbs flexed. In contrast, hypotonic infants may wrap over the
examiner’s arms.

5- scarf sign ( term infants)

taking the baby's hand and pulling it to the opposite shoulder,
in hypotonic infant elbow will cross the midline of the chest
Physical examination.
Mother examination:
- transitory neonatal myasthenia may be suspected if the mother displays
fatiguability of the eyelids with upward gaze or fatiguability of the arms with
sustained forward extension.
- Infants with congenital myotonic dystrophy have severe hypotonia but their
mothers are typically only mildly affected and unaware of their disorder.
Mothers with myotonic dystrophy may show grip myotonia, percussion
myotonia, ptosis and/or distal weakness that they were unaware of.
 Central

Peripheral • depressed level of

consciousness , not
• alert, responds track visually, fail to
appropriately to imitate facial gestures,
surroundings or appear lethargic
• profound distal • Normal power ( normal
weakness ( Paucity or spontaneous
absent spontaneous movements ) or axial
movement ) and weakness
muscle atrophy. • Hyper or normal
• hyporeflexia or areflexia reflexes
• dysmorphic features,
• Fasciculations fisting of the hands,
• normal sleep-wake scissoring on vertical
patterns suspension,
organomegaly .
• Early seizures, apnea,
or exaggerated
irregular breathing
patterns.
Identifying Information.

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Despite being red, Mars It’s a gas giant and the Venus has a beautiful
is actually a cold place biggest planet in the name and is the second
full of iron oxide dust Solar System planet from the Sun
01. Central hypotonia
 Definition
Central hypotonia : Is a condition of decreased muscle
tone that originates from the central nervous system.

It might be generalized and affect the limbs, trunk

and neck or may be localized such that specific areas
of the body are predominantly hypotonic with others
having normal or hypertonic characteristics.
 Causes of central hypotonia .
● 1- Congenital:

● Genetics (Non-syndromic)

• Normal brain development:

• Benign congenital hypotonia :

• Abnormal brain development:

• Structural brain abnoramlities:
Ø Example, Holoprosencephaly

• Metabolic disorders:
Ø Examples, Zellweger syndrome ( peroxisomal disorder)
Ø Glycogen Storage Diseases
Ø Propionic acidemia
Ø Galactosemia
 Causes of central hypotonia .
Genetics

(Syndromic)

1-Prader-Willi syndrome

2-Williams syndrome

3- Edwards syndrome (trisomy 18)

4-patau syndrome (trisomy 13)

5-Down syndrome (trisomy 21)

PWS and trisomy 21 are the most common genetic causes of central
neonatal hypotonia.
 Prader-Willi syndrome

● Very rare and it’s a complex neurodevelopmental disorder due to errors in genomic imprinting
● with loss of imprinted genes that are paternally expressed from the chromosome 15q11-q13
region.

● Sign and symptoms:

● Infancy Poor feeding, low muscle tone, weak cry, diminished reflexes
● Overeating (hyperphagia), early childhood obesity
● Developmental delay Intellectual disability; delayed motor, language development
● Behavioral problems Inflexibility, obsessive-compulsive characteristics
● Low sex hormones in childhood.
● Dysmorphic facial features in childhood
● Almond-shaped eyes, narrow forehead, thin upper lip
● Small hands/feet, short stature
 Prader-Willi syndrome
● Diagnosis :

● History, clinical examination

● Fluorescence in situ hybridization (FISH)
● genotyping, methylation DNA testing

● Treatment :
● Human recombinant growth hormone therapy
● Decrease body weight/fat, increase muscle mass
● Address complications (Thyroid, sex hormone replacement therapy )

● Other interventions :
● Food restriction
● Address complications (Vitamin D, calcium supplements)
Causes of central hypotonia .
● 2- Post-natal:
● Genetics
Infections:
● Acquired • Sepsis
• Meningitis
• Encephalitis
Toxins:
• Drug Intoxication (e.g. Alcohol, Narcotic)
• Heavy Metal Poisoning
• Organophosphate Poisoning
• Anticholinergic exposure
Perinatal Trauma:
• Perinatal asphyxia (HIE)
• Hemorrhage
The approach of work up .
Detailed history and physical examination

Investigation:
For systemic illness, initial investigations should be conducted to rule out life-threatening and
reversible causes.
For infants with neurological causes of hypotonia ,an MRI of the brain +/- EEG should be completed.

For genetic/metabolic causes, additional specialized testing may be needed, including a genetic
screening through karyotype and microarray analysis.
Treatment.
Once the correct diagnosis is confirmed, the cause is treated
first, followed by symptomatic and supportive therapy for the
hypotonia.

Occupational and
Physical therapy speech-language
therapy
can improve fine motor
control and overall body
can help breathing, speech,
strength. andswallowing difficulties

Therapy for infants and young children may also include

sensory stimulation programs.
02. Peripheral hypotonia
1) Anterior horn cell
Spinal muscular atrophy and poliomyelitis
2) Peripheral nerve
Guillain-Barré syndrome , hereditary motor sensory neuropathy
Tick paralysis, Bell palsy
3) neuromuscular junction
Myasthenia gravis (juvenile, transient, neonatal, congenital) , Botulism
4) Muscle
Muscular dystrophy ( Duchenne , Becker ) , myotonic dystrophy , myopathies
1) Anterior horn cell .
Spinal muscular atrophy
Etiology
autosomal recessive disease manifest by progressive degeneration of anterior horn cells.
1) Anterior horn cell .
1) Anterior horn cell .
Spinal muscular atrophy

Laboratory and Diagnostic Studies

genetic testing , Creatine phosphokinase (CK) may be normal or mildly elevated ,
Electromyelogram (EMG) shows fasciculations , Muscle biopsy specimens show grouped atrophy.

Treatment
Definitive therapy
- Nusinersen ( An antisense nucleotide that alters differential splicing of the transcript of the SMN2 gene,
so it produces a functional SMN1 protein , Requires annual intrathecal injections)
- Onasemnogene abeparvovec (An agent based on an adeno-associated virus 9-based vector that carries a
normal copy of SMN1 to the lower motor neurons of the spinal cord , administered intravenously once )
- RIsdiplam ( mRNA splicing modulator that improves the efficiency of SMN2 gene transcription → ↑
systemic SMN protein concentration , Can be given orally )

Supportive therapy
Respiratory support , Nutritional support , Physical rehabilitation , Orthotics to
prevent joint and spine deformities
 Tongue
fasciculation
Will be seen on the
lateral aspect of not
protruded tongue
(best identified by
inspecting the mouth
when the child is
asleep )

Mars Jupiter
Despite being red, Mars It’s a gas giant and the
is actually a cold place biggest planet in the
full of iron oxide dust Solar System
2) Peripheral Nerve

Guillain–Barré Syndrome

Etiology
Post infectious autoimmune peripheral neuropathy that can occur about 10 days after a respiratory or
gastrointestinal infection (classically Mycoplasma pneumonia or campylobacter jejuni) or after taking
vaccines (swine influenza vaccine).

Clinical Manifestations
a. Ascending, symmetric paralysis may progress to respiratory arrest.
b. No sensory loss occurs, although low-back or leg pain may be present in 50% of patients.
c. Cranial nerve involvement. Facial weakness occurs in 40–50% of patients and is often bilateral.
d. Dysautonomia, arrhythmia, orthostatic hypotension, and urinary retention may occur.
e. Miller Fisher syndrome, a variant of Guillain–Barré syndrome, is characterized by ophthalmoplegia,
ataxia, and areflexia.
2) Peripheral Nerve
Guillain–Barré Syndrome

Laboratory and Diagnostic Studies

a. LP shows albuminocytologic dissociation (i.e., increased CSF protein in the absence of an elevated cell
count) which reflects disruption of the blood–CSF barrier due to nerve inflammation.
b. Nerves conduction demonstrates decreased nerve conduction velocity or conduction block.
c. Spinal MRI:
- MRI with gadolinium may reveal enhancement of the spinal nerve roots
- May be necessary in children younger than 3 years to rule out compressive lesions of the spinal cord,
because the sensory examination in children of this age is often difficult to evaluate.

Treatment
Treatment should be initiated as soon as the diagnosis is established because of the risk of respiratory
muscle paralysis.
a. Intravenous immune globulin (IVIG), given for 2–4 days, is the preferred treatment for children because
of its relative safety and ease of use.
b. Plasmapheresis removes the patient’s plasma along with the presumed antimyelin antibodies and is
performed over a 4- to 5-day period.
2) Peripheral Nerve
Guillain–Barré Syndrome
Emergency Management

o Weakness of the respiratory muscles can cause patients with GBS to require artificial ventilation in up to
25% of patients.

o Regular monitor of vital capacity can be useful in determining if prophylactic intubation is necessary.

o Early intubation is recommended for patients for airway protection with guidance using the 20-30-40
rule

- 20-30-40 Rule for Intubation in GBS: Forced vital capacity < 20ml/kg , Max inspiratory pressure <30cm H20
, Max expiratory pressure <40cm H20
3) Neuromuscular junction
Myasthenia Gravis

Etiology
an autoimmune disorder that presents with generalized weakness, fatigability of muscles, ptosis, and
diplopia.
caused by antibodies against the acetylcholine receptor (AChR) in the postsynaptic membrane of the
neuromuscular junctions.

Classification
1. Neonatal myasthenia: a transient weakness in the newborn period secondary to transplacental
transfer of maternal AChR antibodies from a mother affected with myasthenia gravis. Last for ??
2. Juvenile myasthenia gravis: presents in childhood secondary to AChR antibody formation.

Epidemiology Juvenile myasthenia gravis affects girls two to six times more frequently than boys.
 3) Neuromuscular junction
Myasthenia Gravis

Clinical manifestations

Neonatal myasthenia: hypotonia, weakness, feeding problems, and weak cry are the most common findings.

Juvenile myasthenia gravis:

a. Bilateral ptosis: the most common presenting sign.
b. Characteristic increasing weakness occurs later in the day and with repetitive or sustained muscle activity.
c. Diplopia secondary to decreased extraocular movements may be the only manifestation.
d. DTRs are preserved.
e. Other autoimmune disorders, including juvenile rheumatoid arthritis, diabetes mellitus, and thyroid disease, may coexist.
 3) Neuromuscular junction
Myasthenia Gravis

Laboratory and diagnostic studies

1. Tensilon test. Intravenous injection of edrophonium chloride, a rapidly acting cholinesterase inhibitor, produces transient
improvement of ptosis.
2. Decremental response to low-frequency (3–10 Hz) repetitive nerve stimulation
3. Presence of AChR antibody titers

Management
Neonatal myasthenia:
- treatment is supportive because the disorder is self-limited.
- Small feedings by nasogastric tubes and assisted ventilation are provided if needed.
- Cholinesterase inhibitors can be used to aid with feeding and respiratory support.

Juvenile myasthenia gravis treatment involves the following:

a. Cholinesterase inhibitors are the mainstay of treatment. Pyridostigmine bromide is the drug of choice.
b. Immunotherapy
1. Corticosteroids are used when cholinesterase inhibitors fail.
2. Plasmapheresis lowers the level of AChR antibodies.
3. IVIG
c. Thymectomy
 3) Neuromuscular junction
Congenital Myasthenic Syndromes

Etiology
- The congenital myasthenic syndromes (CMS) are due to gene mutations in the components of the neuromuscular junction.
- Familial, not transferred by the mother, not autoimmune mediated.

Clinical manifestations
- Typically present in infancy with hypotonia, ophthalmoparesis, facial diplegia, and extremity weakness, although they can
present throughout childhood.
- Respiratory function and feeding may be compromised.
- Children with CMS usually have lifelong disability.

Diagnosis: Molecular genetic testing

Treatment:
- Depend on the specific subtype of congenital myasthenia.
- Most treatments attempt to improve the signaling between nerve cell and muscle. These drugs include pyridostigmine,
fluoxetine.
3) Neuromuscular junction
Myasthenia Gravis

Neonatal myasthenia Juvenile myasthenia gravis Congenital myasthenia gravis

- Babies born to mothers with - Autoimmune - Very rare

MG - Develops typically in female - Non immune
- Temporary adolescents - Inherited (AR)
- Usually lasts only a few weeks - Life-long condition - Symptoms usually begin in 1st
- May go in and out of remission year and are life-long

* Immunosuppressive therapy does not improve clinical symptoms in CMS, whereas it does in MG
3) Neuromuscular junction

Infantile botulism

Definition
Infantile botulism is bulbar weakness and paralysis that develops in infants during the first year of life
secondary to ingestion of Clostridium botulinum spores and absorption of botulinum toxin.

Etiology
The source of the botulinum toxin is infected foods, such as contaminated honey, or spores unearthed
from the ground. The toxin prevents the presynaptic release of acetylcholine.

Clinical features
1. Onset of symptoms occurs 12–48 hours after ingestion of spores.
2. Constipation is the classic first symptom of botulism.
3. Neurologic symptoms follow, including weak cry and suck, loss of previously obtained motor milestones,
ophthalmoplegia, and hyporeflexia.
4. Paralysis is symmetric and descending, and at times, diaphragmatic paralysis
may also occur.
3) Neuromuscular junction

Infantile botulism

Diagnosis
- Suggestive history
- Neurologic examination
- Identification of the toxin or bacteria in the stool
- EMG is sometimes performed and demonstrates brief, small-amplitude muscle potentials with an
incremental response during high-frequency stimulation.

Management
- Treatment is supportive, with nasogastric feeding and assisted ventilation as needed.
- Botulism immune globulin improves the clinical course.
- Antibiotics are contraindicated and may worsen the clinical course.
4) Muscle

Duchenne and Becker Muscular Dystrophies (DMD, BMD)

Muscular dystrophies are a group of genetic muscle diseases characterized by progressive myofiber
degeneration and the gradual replacement of muscle by fibrotic tissue.

Duchenne muscular dystrophy:

The most common muscular dystrophy.
X-linked disorder.
Arises from a mutation in the dystrophin gene.
More severe than BMD.

Becker muscular dystrophy: an allelic disorder associated with more mild symptoms; its mutations at least
partially preserve the function of the resulting gene product.
4) Muscle
Duchenne and Becker Muscular Dystrophies (DMD, BMD)
Clinical manifestations

1. Slow, progressive weakness affecting the legs first

2. In DMD, children lose the ability to walk by around 12 years of
age. In BMD, patients lose the ability to walk by 20 or more years of
age.
3. Pseudohypertrophy of calves (due to replacement of muscle
fibres by fat and connective tissue): more common in DMD than in
BMD.
4. Gowers sign
5. Cardiac involvement (e.g., cardiomegaly, tachycardia, or cardiac
failure) occurs in 50% of patients.
6. Mild cognitive impairment may occur in DMD, but normal
intelligence is present in BMD.
4) Muscle
Duchenne and Becker Muscular Dystrophies (DMD, BMD)
Laboratory a diagnostic studies

1. The presence of enlarged calf muscles in a young boy with muscle weakness suggests the diagnosis.
2. CK levels are VERY high, even before muscle weakness.
3. EMG shows small, polyphasic muscle potentials with normal nerve conductions.
4. Muscle biopsy shows the typical dystrophic pattern.
5. Absent or decreased dystrophin levels are present on immunocytochemistry or Western blot assay of
muscle.
6. DNA testing may reveal the gene deletion in >90% of patients

Treatment

- Chronic oral steroid therapy: to slow the pace of the disease, delay motor disability, and improve
longevity.
- Supportive care: physical therapy, bracing, proper wheelchairs, and treatment of cardiac dysfunction or
pulmonary infections.
- Eteplirsen: acts to promote dystrophin production
- A multidisciplinary approach is recommended
4) Muscle
Myotonic Dystrophy

Second most common muscular dystrophy , autosomal dominant genetic disease

Caused by progressive expansion of a triplet repeat, CTG, in the DM protein kinase gene.

Childhood-onset “classic” DM:

- Slowly progressive facial and distal extremity weakness
- Myotonia (a disorder of muscle relaxation after contraction)
- Facial appearance is characteristic, with hollowing of muscles around temples, jaw, and neck; ptosis;
facial weakness; and drooping of the lower lip.
- The voice is nasal and mildly dysarthric.
- Arrhythmias, endocrinopathies, immunological deficiencies, cataracts, and intellectual impairment
4) Muscle
Myotonic Dystrophy

Congenital DM:
- Occurs in a baby born to a mother with symptomatic disease
- Infants are immobile and hypotonic, with ptosis, absence of sucking and Moro reflexes,
poor feeding, and respiratory difficulties.
- Affected infants have an inverted V-shaped upper lip
- Antenatal history may reveal decreased fetal movements and polyhydramnios caused by
poor swallowing in utero.
- Examine the mother (myopathic facies, shake hand as myotonia prevents the
prompt release of grip, percussion with a reflex hammer, by tapping thenar, wrist
extensor will produce involuntary muscle contraction with a delay in relaxation,
called percussion myotonia).

Diagnostic studies :
Genetic testing ( gold standard): presence of an expanded CTG repeats in the DMPK gene

Treatment: supportive
Case scenario
Q1) You are called to the nursery to examine a “floppy” female infant born within the past 24
hours. The neonate is hypotonic with diminished deep tendon reflexes. There are no tongue
fasciculations. When you greet the baby’s mother, she is anxious and has difficulty releasing her
grip after shaking your hand. Which of the following is the most likely diagnosis?

A. Muscular dystrophy
B. Congenital myotonic dystrophy
C. Neonatal myasthenia gravis
D. Spinal muscular atrophy, type 1
E. Infantile botulism
Q2) A 6-month-old male infant is evaluated for lethargy and poor feeding. Recent dietary
changes include the introduction of cereals, fruits, and herbal tea with honey. Physical
examination reveals an afebrile infant with normal vital signs. Neurologic examination is notable
for decreased muscle tone and a weak suck. Which of the following statements regarding this
infant’s most likely diagnosis is most accurate?

A. Infants typically present with ascending paralysis.

B. Antibiotics should be administered immediately. C. Infants present with brisk deep tendon
reflexes.
D. Electromyography is not helpful in making the diagnosis.
E. Constipation is often the initial symptom in infants
References.
● Nelson essential of paediatrics 8th edition
● A schematic approach to hypotonia in infancy , JoAnna Leyenaar MD MPH, Peter Camfield
MD FRCPC, Carol Camfield MD FRCPC

● The Floppy Infant: Evaluation of Hypotonia , Dawn E. Peredo, MD,*Mark C. Hannibal, MD

● Manual of clinical paediatric – AlHawasi
● AMBOSS
● Sarah Bagher (2009). Central hypotonia .
https://www.kau.edu.sa/files/165003/files/48267_central%20hypotonia.pdf

● https://www.osmosis.org/notes/Imprinting_disorders#page-1

● Board Review Series

● http://www.emdocs.net/guillain-barre-syndrome-third-times-charm/
● https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338848/