Hypotonia

Contracture
Areflexia UMN
Babinski Brain-> Spinal Cord
Contracture
Hypertonia (Early hypotonia)
Reduced Power
Hyperreflexia
Clonus
Upgoing Babinski

LMN
DRG-> Muscle
Hypotonia
Long-term contracture

Tay Chee Geap

Hyporeflexia/Areflexia
Proximal Myopathy
Babinski downgoing

Cerebellar
Hypotonia
 End of this session:

◦ Able to differentiate central vs peripheral

hypotonia

◦ Able to evaluate floppy infants

◦ Able to understand investigations for

hypotonic/floppy infants
Introduction

 The word “Floppy” :

◦ Decrease in muscle tone (hypotonia)
◦ Decrease in muscle power (weakness)
◦ Ligamentous laxity and increase joint mobility

◦ Strictly speaking: floppy = hypotonia

 Tone: resistance to passive movement
Stretch reflex controls the muscle tone.

 Power: resistance to active movement

 Tone is important to maintain normal posture

against antigravity

 Assessed by looking at the infant’s posture in

supine, ventral and vertical suspension and in
traction.
UMN: hypertonia dt disinhibition
Early phase: Hypotonia
 C

D
Classification/ Localisation

 Central vs Peripheral

 Paralytic vs non-paralytic

 Upper motor neuron vs lower motor neuron

Cerebellar: HYPOtonia

Fibre: Fascilitatory fibre

Features of hypotonia:

 Full abduction and external rotation of legs

 Flaccid extension of arms
Prominent head lag Type:Term
scarf sign

 Scarf sign Definitions

Vertical suspension age

1. sign used in Dubowitz scoring (q.v.) to assess developmental
 and muscle tone in neonates. The infant's arm is pulled
laterally across the chest; in the hypotonic infant, the elbow will

 Horizontal suspension cross the midline; in a term infant with normal tone, the elbow
will not reach the midline.

 Flat occiput ? Dt not turning head

 Congenital dislocation of hips
 Arthrogryposis Congenital joint contracture Contracture
movement
dt intrauterine reduced

 Paradoxical breathing
Acute encephalopathies Connective tissue disorders
 Birth trauma  Ehlers-Danlos syndrome

 Hypoxic-ischaemic  Osteogenesis imperfecta

encephalopathy  Congenital ligamentous laxity

 Benign congenital hypotonia
 Hypoglycaemia

Chronic encephalopathies
• Cerebral malformations
• Hypotonic cerebral palsy
• Inborn errors of metabolism (mucopolysaccharidoses,aminoacidurias,
organic acidurias, lipidoses, glycogen storage diseases, mitochondrial
diseases and Menkes syndrome)
• Chromosomal disorders (Prader-Willi syndrome, Trisomy 21)
• Genetic disorders (familial dysautonomia, Lowe synd)
• Peroxisomal disorders (neonatal adrenoleukodystrophy, Zellweger syndr)
• Endocrine/Nutritional(hypothyroidism, rickets, renal tubular acidosis)
 Spinal muscular atrophy
 SMA Type 1 e Werdnig-Hoffmann
disease
 Chronic SMA e Type 2 & 3
 SMARD 1
 Paralytic poliomyelitis
 Neuropathies
 Hereditary motor-sensory
neuropathy
 Congenital hypomyelinating
neuropathy
 Acute demyelinating polyneuropathy
 Neuromuscular junction problems
 Botulism
 Transient neonatal myasthenia
 Autoimmune myasthenia
 Congenital myasthenic syndromes
Muscular disorders
 Congenital myopathies (nemaline
rod myopathy, myotubular
myopathies, central core disease,
minicore disease, Bethlem and
Ullrich myopathies)
 Congenital muscular dystrophies
(CMD) (Walker-Warburg,
Fukuyama, muscle-eye-brain
disease, merosin-positive CMD,
etc)
 Congenital myotonic dystrophy
 Metabolic myopathies (acid
maltase deficiency, phosphorylase
deficiency, mitochondrial
myopathy
 Endocrine myopathies
(hypothyroidism
Conditions where central and
peripheral hypotonia may co-exist
• Familial dysautonomia
• Hypoxic-ischaemic encephalopathy
• Infantile neuroaxonal degeneration
• Lipid storage diseases
• Lysosomal disorders
• Mitochondrial disorders
• Perinatal asphyxia secondary to motor unit
disease
Approach
 central (“floppy strong”) vs peripheral
◦ 60-80% vs 15-30%

History taking
12
 1/12 lower limb weakness
Examination: Gower’s Sign, foot and
plantar weakness, hi stepping gait
Distal>> Prox

 Clinical evaluation Areflexia

Generalised muscle wasting

◦ Genetic aspect Charcot-Marie-Tooth

◦ Neurological assessment Pathophysiology: Limb-girdle weakness

 Laboratory investigation
History
 At least a three generation pedigree
(consanguinity, previous miscarriages and early childhood deaths,
neuromuscular, metabolic or genetic conditions in siblings)
 Prenatal risk factor
 History of drug & teratogen exposure
 Breech presentation Birth mode +/-
 Reduced fetal movement instrumentation
 Polyhydramnios
 Perinatal insult (HIE/asphyxia, seizure)
 Low apgar scores (tone, reflex, respiration)
 length of umbilical cord Short UC means not moving intrauterine
 Feeding/cough or breathing problems
Apgar Score: does n not predict child outcome
Maternal morphine/pethidine Baby’s conditon / adaptation to extrauterine
condition.
 Grip or percussion myotonia, facial weakness:
congenital myotonic dystrophy

 Mild facial weakness: the mother of a boy with

X-linked myotubular myopathy

 Fatiguability, ptosis: in a mother with

myasthenia gravis
Neurological assessment: infant
 Alertness; depressed level of consciousness/lethargy
 Myopathic facies (open mouth with tented upper lip, poor lip seal
when sucking, lack of facial expression)
 High & tented arch palate: congenital myopathy
 Large tongue: storage ds
 Tongue fasciculation: anterior horn cell ds
 Ptosis, external ophthalmoplegia: congenital myasthenic syndrome
 Weak cry
 Axial hypotonia
 lack of antigravity movement: neuromuscular
 Other features: Respiratory problems, recurrent apneas, feeding
difficulties (drooling/pooling of secretions), joint contractures
 Absence or depressed deep tendon reflexes
 High and
tented arch
palate

Myopathic face

High arch
only
Genetic assessment: infant
 Dysmorphic features/syndromic
◦ Dolicocephaly, almond shaped eyes, undescended testes: PradereWilli syndrome
◦ Epicanthic folds with periorbital fullness, stellate irises and midface hypoplasia:
Williams syndrome
◦ Down syndrome

 Eye:
◦ catatacts, pigmentary retinopathy (peroxisomal disorder)
◦ Len dislocation (sulfite oxidase/ molybdenum cofactor deficiency)

 Abnormal fat pad & inverted nipples (CDG)

 Cardiomyopathy (pompe; carnitine def; FAOD)

 Bilateral 2nd & 3rd toe syndactyly (SLOS)

 Hepatomegaly/hepatosplenomegaly (storage ds)

 Renal cysts (peroxisomal disorder)

 Abnormal odour: metabolic disorder

Investigation
1. General
2. Metabolic
3. Genetic
4. Neurophysiologic
5. Imaging
Investigation > General
 FBC
 Renal profile, Ca
 Thyroid function test
 TORCH screen
 Urine CMV
 Evaluation for sepsis: culture of blood, urine
and CSF
Investigation > metabolic
aspect
 Toxic encephalopathies
◦ Eg: amino acidemia, urea cycle defect, organic aciduria

 Energy deficient encephalopathies

◦ Eg: mitochondrial disorder, FAOD

 Disorder involving intracellular processing of

Complex molecules
◦ Eg: peroxisomes, glycogen, CDG
Investigation : metabolic aspect
 Ammonia: urea cycle defect, organic aciduria, FAOD
 Lactate: carbohydrate metabolism, mitochondrial
disorder
 Serum amino acid: aminoacidopathies
 Urine organic acid & acylcarnitine profile: organic
aciduria, FAOD
 Very long chain fatty acid: peroxisomal disorder
 Uric acid: normal in sulfite oxidase def; low in
molybdenum co-factor def
 Isoimmune electrophoresis for Transferrin: CDG
 7-dehydrocholesterol: SLOS
 Acid alpha-glucosidase : pompe
Investigation > Genetic aspect:
◦ Karyotyping
◦ Fluorescence in situ hybridization (FISH)
◦ New technique:
 Array CGH (additional 5-17% vs conventional method)
 Expensive
 Unable to detect balance rearrangements (translocation &
inversion) “Anology”
Missing pages or arranged in
 Unclear clinical significance alphabetical order or not
 Second generation sequencing studies (exome
sequencing)
 High cost
 Genetic heterogeniety
 Polymorphic variants
Investigation: Imaging &
neurophysiology
 Creatine kinase
 Brain imaging:
◦ CT
◦ MRI, MR spectroscopy

 Nerve conduction study

 Electromyography
 Electroencephalography

 Muscle biopsy:
◦ HPE
◦ Electron microscopic examination
◦ Respiratory chain enzyme studies
Management

Definitive vs supportive
SMA & DMD

genetic therapy: change to a
milder genotype/phenotype

 Definitive
◦ Enzyme replacement therapy
◦ Many on research bases:
 antisense oligonucleotide therapy

Supportive:
multidisplinary
Paro-Panjan et al, Journal of Child Neurology 2004
Selected condition with
hypotonia as a main feature….
1. Genetic & Chromosomal abnormality :
I. Down syndrome
II. Prader willi syndrome
III. Fragile X syndrome
IV. 1p36 deletion
V. 22q13 deletion
VI. 22q11.2 deletion
VII. William syndrome
VIII. Smith-Magenis syndrome (17p- syndrome)
IX. Wolf-Hirschhorn syndrome
X. Kabuki syndrome
XI. Sotos syndrome
2. Normal brain: non-syndromic mental
retardation

3. Brain anomalies:
I. AGS,
II. Lissencephaly,
III. holoprosencephlay,
IV. corpus callosum agenesis,
V. Miller-Dieker syndrome,
VI. Joubert syndrome,
VII. unclassified cerebral dysgenesis
VIII. Leukoencephalopathies
4. Motor unit hypotonia
A. Anterior horn cell: SMA
B. Peripheral neuropathies
C. Neuromuscular junction
D. Muscle
i. Congenital muscular dystrophies
ii. Congenital myotonic dystrophies
iii. Congenital myopathies
5. Metabolic
A. Urea cycle defect
I. CPS def
II. OTC def
III. Citrullinemia
IV. Arginoacid lyase def
V. Arginase def

B. Organic acidemia
I. Propionic acidemia
II. Methymalonic acidemia

C. Congenital disorder of glycosylaton: Jaeken

syndrome

D. Glycogen storage ds: pompe

E. Primary carnitine def
F. Molybdenum cofactor def, sulfite oxidase def
G. GM1 gangliosidosis
H. Disorder of creatine metabolism: GAMT def,
creatine transporter def
I. Mitochondrial myopathies