An Overview of Neuromuscular Disorders of
Childhood
Dr David Webb
Consultant Paediatric Neurologist
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The Floppy Infant
Progressive Limb Girdle Weakness
Progressive Distal Weakness
Acute Generalised Weakness
THE FLOPPY INFANT
Central Hypotonia
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Seizures
Global Delay
Dysmorphic Features
Strabismus
Anti-gravity Movement
Brisk Reflexes, Clonus
Extensor Hypertonus
Fisting
Scissoring
Central Hypotonia - “Floppy” Infant
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Chromosomal
Cerebral Malformations
Encephalopathies
Genetic Syndromes
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Prader Willi
Oculocerebrorenal
Familial Dysautonomia
Metabolic
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Peroxisomal (Zellwegers)
Lysosomal (GM1, Pompes)
Cholesterol (Smith Lemli Opitz)
Prader Willi Syndrome
 Genetics
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15q deletion
Uniparental Disomy (paternal)
Clinical
Hypotonia, CDH, TEV
Nasogastric Feeding
Cryptorchidism
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Hypogonadism
Mental Retardation
Short, Obese
Peripheral Hypotonia
Alert Infant
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Muscle Atrophy
Fasciculation’s
Weakness - no anti-gravity
Reduced, absent reflexes
Peripheral Hypotonia - “Floppy” Infant
Spinal Cord Lesion
Spinal Muscular Atrophy (SMA)
Polyneuropathy
Myasthenia
Congential Muscular Dystrophy
Myopathy *congenital
*inflammatory
*metabolic/endocrine
Infantile SMA
Classification
1. Onset < 3 mths
2. Onset 3 - 18 mths
3. Onset > 18 mths
never sit
never stand
walk don’t run
Clinical Type 1
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Atrophy + Fasciculation’s
Weakness + Areflexia proximal, legs> arms, eyes + diaphragm spared
Paradoxial breathing
Genetics
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AR, 5q 12.1
Deletion Analysis
Investigations
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CK + NCS – normal
EMG - Fibrillations
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ECG - baseline tremor
Muscle Bx - denervation
Fiber grouping + atrophy
Type II fiber hypertrophy
Congenital Muscular Dystrophy
Classification
1. Pure
merosin (+) / merosin (-)
2. Fukuyama
mental retardation
3. Walker Warburg muscle eye brain disease
Clinical
Merosin (+) normal MRI
Merosin (-) abnormal MRI
good outcome
Usually don’t walk
Congenital Myopathies
Classification
1.
2.
3.
4.
Central core
Disproportion
Myotubular
Nemaline
AD
?
XL/AD
AD
Investigations
CK - normal
EMG -+/- myopathic
Muscel BX
Type I fibre
Predominance + atrophy
Neonatal Metabolic Myopathies
Deficiency
Aetiology
Acid maltase
Carnitine
Cyto. C Oxidase
Glycogen SD
FA oxid defect
Mithochondrial
Cardiomegaly
Cardiomegaly
Lactic acidosis
Progressive Limb Girdle Weakness
Spinal Cord Lesion
Juvenile SMA
Myasthenia
Muscular dystrophy
Myopathy
inflammatory
congenital
metabolic/endocrine
Muscular Dystrophies
DMD
Becker
Limb G
FSH
MD
ED
Gene
XL
XL
AR
AD
AD
XL
Onset
0-5
5-15
10-30
10-30
10-30
5-15
Pattern
Proximal
Proximal
Proximal
Prox arm/face
Distal limb/face
Prox arm/distal leg
DUCHENNE MUSCULAR DYSTROPHY
Clinical
Delayed “Toe” walking
Frequent falling
Waddling gait
Gowers sign
Calf hypertrophy
Lumbar lordosis
Prognosis
Lose walking 7 - 13yrs
Cardiomyopathy
Scoliosis
Respiratory Failure
IQ average 85
Investigations
Raised CK (x10)
Muscle biopsy
EMG
Mutation analysis
Intragenic deletion (70%)
Duplications
Treatment Aims
Maintain function
Prevent contractures
Psychological support
Physio + orthoses
Prednisolone
Nocturnal CPAP
1/4000
Xp21 1/3 new mutation
Dystrophin - muscle cell wall integrity
Ca+ ion influx
Ca+ calmodulin complex breakdown
Excess free radicals - muscle cell destruction
FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY
Clinical
Shoulder girdle + face
Insidious + variable phenotype
“Late” distal leg weakness
retinal vascular abnormalities
hearing loss
Pathology
Gene 4q35
Penetrance complete
FSH/ scapuloperoneal
+/- denervation
LIMB GIRDLE MUSCULAR DYSTROPHY
Mild Form
Gene Loci
AR
AD
15q, 2p
5q
Severe Form
SCARMD - 13q, 17q
Onset 3 - 12 yrs
Adhalin (-opathy)
MYOTONIC DYSTROPHY
Neonatal
Polyhydramnios
Difficult labour
Respiratory failure
Facial + proximal weakness
Arthogryposis
Feeding difficulties
Diagnosis
Mother always affected
Outcome
Cardiomyopathy
Physical handicap
Low IQ
Adolescent
Facial + distal weakness
Myotonia
Cataracts
Frontal balding
Endocrinopathies
Diagnosis
Triplet repeat - 19q13.3
CK raised
EMG - myotonia
Muscle Bx - type 1 atrophy
Myasthenic Syndromes
Neonatal myasthenia
Transient (AchR Ab+)
Genetic (AR)
Limb gridle myasthonia
Familial limb girdle
Slow channel syndrome
Myasthenia Gravis
Ocular, generalised fatiguability
Diagnosis
Tensilon test, EMG, Antibodies
Management
Neostigmine
DERMATOMYOSITIS
Clinical
Weakness - neck, trunk, proximal limb, bulbar
Rash - race, extensor, periorbital oedema
Miserable and tender
Contractures, calcinosis
Pathology
Small vessel vasculitis
Management
Steroids, Igs, azathioprine, cyclosporin
Progressive Distal Weakness
Spinal Cord lesion
Juvenile SMA/ ALS
Neuropathies
Myopathies
Distal hereditary/myotonic dystrophy
Bethlem/Emery dreifuss
Scapuloperoneal/Scapulohumeral
Neuropathies
1.
Hereditary
HSMN 1-4
Leukodystrophies
Mitochondrial, Giant axonal, familial amyloid
2.
Acquired
Chronic demyelinating
Systemic (drugs, vasculitic, toxic)
Acute Generalised Weakness
Anterior horn cell - enteroviruses (polio)
Neuropath
- Guillain Barre
Neuromuscular Jn - botulism, tick paralysis
Muscle
- acute myositis
- metabolic (porphyria, tyrosinemia)
- periodic paralysis