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8/3/2019 Revised Floppy Infant
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Floppy Infant
Fares Kokash,MD
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DefinitionDefinition Floppiness is a term
used to describebabies who havemarked muscle
hypotonia.
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The focus of this talk is primarily on the
diagnostic aspects, although we have notmentioned therapeutic aspects, these
.
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AssessmentAssessment
Perinatal risk factors:
Birth trauma Birth anoxia Deliver com lications
Low APGAR scores (tone, reflexes and respiratory effort) Onset of the hypotonia Short umbilical cord (poor fetal movement or immobility) Abnormal fetal presentation (breech)
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Clinical presentation of muscleClinical presentation of musclehypotonia and weaknesshypotonia and weakness
Posture of full abduction and externalrotation of the legs as well as a flaccidextension of the arms.
When traction is delivered to the arms,there is a prominent head lag.
The presence of a typical myopathicfacies and paucity of facial expressionare common in hypotonic infants
Low-pitched cry / progressively weaker
cry, readily distinguished from thevigorous cry of a normal infant.
Paucity of antigravity movements
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Differential DiagnosisDifferential Diagnosis: Upper Motor Neuron Causes Chromosomal
Turner's Syndrome
Down's Syndrome Prader-Willi Syndrome
Infection Sepsis Meningitis Encephalitis
Metabolic
Differential Diagnosis: Lower Motor Neuron Causes Brainstem or spine
Spinal muscular atrophy (Anterior Horn
Cell Disorder) Infection Poliomyelitis Coxsackie Virus
Neuromuscular Junction Congenital Myasthenia Gravis Myasthenic syndrome
Hypocalcemia Hyponatremia Hypermagnesemia Hypoglycemia Hypothyroidism Aminoaciduria Gangliosidoses Hepatic Encephalopathy or Reye's
Syndrome Toxin Drug Intoxication (e.g. Alcohol, Narcotic) Heavy metal poisoning Organophosphate Poisoning Anticholinergic exposure
Perinatal trauma Perinatal asphyxia (HIE)
Hemorrhage
Botulism
Neyve: -Guillain Barre Syndrome
Muscle Muscular Dystrophy Congenital Myopathy Inflammatory Myopathy
Other
Tick Paralysis Benign congenital hypotonia
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Localization of hypotonia and weaknessLocalization of hypotonia and weakness
The neurological examination directs the clinician inlocalizing the site of the lesion to the
Central (UMN)
Peripheral lower motor unit (LMN) Neuromuscular junction muscles
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UMN LMN
DTRs increased Decreased orabsent
Muscle tone increased decreased
Muscle atrophy non +
Fasciculation non +
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Clinical characteristics of muscleClinical characteristics of musclehypotonia and weaknesshypotonia and weakness
Central hypotonia
Weakness is uncommon except in the acute stages,and usually it is axial weakness
obtundation and depressed level of consciousness
Hyperreflexia
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Infants with severe CNS abnormalities develop signs of hypotonia inaddition to
impairment in level of consciousness feeding difficulties seizures apneas
a norma pos ur ng
abnormalities of ocular movements and of brain stem reflexes
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Clinical characteristics of muscleClinical characteristics of musclehypotonia and weaknesshypotonia and weakness
Disorders of LMN
The presence of profound weakness as well ashypo/areflexia
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Clinical characteristics of muscleClinical characteristics of musclehypotonia and weaknesshypotonia and weakness
neuromuscular disease
combination of weakness in the antigravity limb
muscles and hypo/areflexia together
Involvement of bulbar and occulomotor muscles
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Clinical characteristics of muscleClinical characteristics of musclehypotonia and weaknesshypotonia and weakness
Such a clear distinction, however, may not always bepossible and the features may overlap in conditionswhere the pathology affects both the CNS andperipheral nerve (PelizaeusMerzbacher disease,leukod stro hies
The presence of characteristic patterns of regionalweakness may favor certain etiologies
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Additional clinical clues to differential diagnosisAdditional clinical clues to differential diagnosis
A high arched palate is often noted in infants with neuromusculardisorders
the tongue may be large in storage disorders (acid maltase/Pompedisease)
the presence of tongue fasciculation suggests anterior horn cellinvolvement and denervation
Visceral enlargement (suggests storage disorders)
inverted nipples (congenital disorders of glycosylation)
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Additional clinical clues to differential diagnosisAdditional clinical clues to differential diagnosis
Ptosis, external ophthalmoplegia (myasthenic syndromes)
Cataracts, renal cysts, pigmentary retinopathy (peroxisomal
Lens dislocation (sulfite oxidase/molybdenum cofactor
deficiency)
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Additional clinical clues to differential diagnosisAdditional clinical clues to differential diagnosis
Arthrogryposis: the presence of severe weakness in early fetal
development, which immobilizes joints, resulting in contractures. Thiscan be a feature encountered in both neurogenic and myopathicdisorders.
eurogen c sor ers are assoc a e w a g er nc ence o o er
congenital anomalies
Myopathic features are less likely to be associated with other defects.
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Laboratory investigationsLaboratory investigations Appropriate and cost effective use of laboratory investigations
to establish a specific etiologic diagnosis is always desirable.
The history and physical assessment will point out the possibleetiology and the indications for relevant diagnostic tests.
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Evaluation of central CNS disorders
Brain MRI
EEG
Genetic tests
Infection screen CSF neurotransmitters
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Evaluation of motor unit disorders
DNA-based testing
Edrophonium chloride Electrodiagnosis
NCS
Repetitive stimulation
Muscle biopsy
Nerve biopsy
Serum CK
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Laboratory investigationsLaboratory investigations We suggest a systematic approach based on the tests currently
utilized in the evaluation of infants with hypotonia:
infants with pure hypotonia of central or peripheral origin
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infants with pure hypotonia of central or peripheral origin
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infants with hypotonia and multisystem features (hypotoniaplus)
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Etiological considerations Central Nervous System:1. Chromosomal disorders2. Metabolic inborn errors3. Structural CNS malformations
1. congenital malformations (lissencephaly, holoprosencephaly)
2. acquired disorders (birth trauma, hypoxic ischemic encephalopathy)
Periphral Nervous System Motor neuron disorders:1. SMA
Disorders of eri heral nerves:1. Peripheral neuropathies
Disorders of the neuromuscular junction:1. Myathenia Syndromes:congenital,transient2. Infantile botulism3. Neonatal hypermagnesemia
Disorders with prominent muscle involvement:1. Congenital myopathies2. Congenital muscular dystrophies3. Metabolic myopathies4. Congenital myotonic dystrophy
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Chromosomal abnormalities
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Etiological considerations Central Nervous System:1. Chromosomal disorders2. Metabolic inborn errors3. Structural CNS malformations
1. congenital malformations (lissencephaly, holoprosencephaly)
2. acquired disorders (birth trauma, hypoxic ischemic encephalopathy)
Periphral Nervous System Motor neuron disorders:1. SMA
Disorders of eri heral nerves:1. Peripheral neuropathies
Disorders of the neuromuscular junction:1. Myathenia Syndromes:congenital,transient2. Infantile botulism3. Neonatal hypermagnesemia
Disorders with prominent muscle involvement:1. Congenital myopathies2. Congenital muscular dystrophies3. Metabolic myopathies4. Congenital myotonic dystrophy
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Metabolic disorders presenting with severe hypotonia in infancyMetabolic disorders presenting with severe hypotonia in infancy
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Etiological considerations Central Nervous System:1. Chromosomal disorders2. Metabolic inborn errors3. Structural CNS malformations
1. congenital malformations (lissencephaly, holoprosencephaly)
2. acquired disorders (birth trauma, hypoxic ischemic encephalopathy)
Periphral Nervous System Motor neuron disorders:1. SMA
Disorders of eri heral nerves:1. Peripheral neuropathies
Disorders of the neuromuscular junction:1. Myathenia Syndromes:congenital,transient2. Infantile botulism3. Neonatal hypermagnesemia
Disorders with prominent muscle involvement:1. Congenital myopathies2. Congenital muscular dystrophies3. Metabolic myopathies4. Congenital myotonic dystrophy
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Structural CNS malformations/encephalopathies
This category includes:
congenital malformations of the nervous system(lissencephaly, holoprosencephaly)
In the majority of instances in this group of disorders,ypo on a s rare y e so e ea ure a presen a on o er
features such as seizures, craniofacial dysmorphisms)
acquired disorders (birth trauma, hypoxic ischemic
encephalopathy) that are associated with profoundhypotonia in the neonatal period.
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Etiological considerations Central Nervous System:1. Chromosomal disorders2. Metabolic inborn errors3. Structural CNS malformations
1. congenital malformations (lissencephaly, holoprosencephaly)
2. acquired disorders (birth trauma, hypoxic ischemic encephalopathy)
Periphral Nervous System Motor neuron disorders:1. SMA
Disorders of eri heral nerves:1. Peripheral neuropathies
Disorders of the neuromuscular junction:1. Myathenia Syndromes:congenital,transient2. Infantile botulism3. Neonatal hypermagnesemia
Disorders with prominent muscle involvement:1. Congenital myopathies2. Congenital muscular dystrophies
3. Metabolic myopathies4. Congenital myotonic dystrophy
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Disorders affecting motor neuron and peripheral nervesDisorders affecting motor neuron and peripheral nerves
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Motor neuron disordersMotor neuron disorders Spinal muscular atrophy (WerdnigHoffman disease):
is AR disorder involving the degeneration of the anterior horn cells
hypotonic and weak, at birth or soon after poverty of spontaneous movements abnormal posture typical for a floppy infant
tongue fasciculation and absent deep tendon reflexes, mild contracturesand decreased fetal movements before birth
the weakness usually involves the bulbar and respiratory muscles,causing significant respiratory distress and infants develop pneumoniaand respiratory failure.
The diagnosis is often clinical EMG usually shows spontaneous fibrillation potentials at rest Muscle biopsy shows grouped neurogenic atrophy and evidence of
presence of hypertrophic type I myofibres (rennervation) DNA based molecular diagnostic tests
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Etiological considerations Central Nervous System:1. Chromosomal disorders2. Metabolic inborn errors3. Structural CNS malformations
1. congenital malformations (lissencephaly, holoprosencephaly)
2. acquired disorders (birth trauma, hypoxic ischemic encephalopathy)
Periphral Nervous System Motor neuron disorders:1. SMA
Disorders of eri heral nerves:1. Peripheral neuropathies
Disorders of the neuromuscular junction:1. Myathenia Syndromes:congenital,transient2. Infantile botulism3. Neonatal hypermagnesemia
Disorders with prominent muscle involvement:1. Congenital myopathies2. Congenital muscular dystrophies
3. Metabolic myopathies4. Congenital myotonic dystrophy
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Disorders of the neuromuscular junctionDisorders of the neuromuscular junction
The following disorders affecting the neuromuscular junction can beconsidered in the differential diagnoses of the floppy infant:
congenital myasthenic syndromes
Transient myasthenic syndrome
Hypermagnesemia of the newborn
Infantile botulism
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myasthenia syndromemyasthenia syndrome Infants presenting with the myasthenia
syndrome share several features including: hypotonia
facial diplegia
ptosis feeding difficulties
apnea
respiratory difficulties generalized weakness
progressively weakening cry
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Congenital myasthenic syndromeCongenital myasthenic syndrome
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Transient myasthenic syndrome
The disorder occurs in infants born to mothers with myastheniagravis.
The acetylcholine receptor (AchR) antibody that causes MG crossesthe placenta and exerts a blocking effect that is responsible for theinterference with neuromuscular transmission.
The symptoms caused are temporary and recovers in about 6 weeks.
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Hypermagnesemia of the newborn
Elevated magnesium levels can be encountered inthe newborn following treatment of maternal eclampsia with magnesium sulfate or
use of magnesium antacids in the newborn
Clinically: encephalopathic infant with hypotonia,depressed deep tendon reflexes, abdominaldistension due to ileus and irregularities of cardiacrhythm.
Elevated magnesium levels result in impairedneuromuscular transmission.
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Infantile botulism
usually occurs within 6 weeks to 1 year after birth
usually in situations where the infant has been fed honeycontaminated with spores of the C. botulinum.
The first s m tom is usuall consti ation. Later, listlessness, ptosis, facial weakness, decreased eye movements
and feeding difficulties, and progression to respiratory failure occur.
rapid repetitive stimulation : presence of small amplitude motorpotentials and an incremental response noted to is pathognomonic.
Stool study may also be helpful in confirmation, but the results areusually delayed.
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Etiological considerations Central Nervous System:1. Chromosomal disorders2. Metabolic inborn errors3. Structural CNS malformations
1. congenital malformations (lissencephaly, holoprosencephaly)
2. acquired disorders (birth trauma, hypoxic ischemic encephalopathy)
Periphral Nervous System Motor neuron disorders:1. SMA
Disorders of eri heral nerves:1. Peripheral neuropathies
Disorders of the neuromuscular junction:1. Myathenia Syndromes:congenital,transient2. Infantile botulism3. Neonatal hypermagnesemia
Disorders with prominent muscle involvement:1. Congenital myopathies2. Congenital muscular dystrophies
3. Metabolic myopathies4. Congenital myotonic dystrophy5. Endocrine myopathies
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Musculardystrophies
Congenitalmyopathies
Course progressive
non-progressive
wasting progressive
CK significantlyelevated
normal orslightly elevated
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Muscular dystrophies
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Congenital myopathiesCongenital myopathies
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ConclusionsConclusions The practicing clinician faced with the challenge of
making a diagnosis in a floppy infant needs to be aware
of the various etiologies availability of specific diagnostic tests the role of supportive investigations
in order to facilitate this process in a speedy and costeffective way.
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ConclusionsConclusions A detailed history and physical examination can help
sort the issue of isolated hypotonia, from the
hypotonic/dysmorphic infant with multisystemmanifestations.
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ConclusionsConclusions The floppy infant poses a chronic neurological problem
demanding multidisciplinary skills and support for both
diagnosis and management.
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ConclusionsConclusions Establishing a specific diagnosis in each case is
important
anticipated outcome for the condition genetic counselling (parents and family members).