Transcript Hypotonia, neuropathies and myopathies

Hypotonia, neuropathies
and myopathies
Aims
• Able to take a history to work out if has
neuromuscular problem
• Know some of the common causes of
hypotonia, neuropathies and myopathies
• Able to think about relevant investigations
Reasons for referral
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Delay in motor milestones
Abnormal gait
Tendancy to fall
Overt muscle weakness, floppiness or
hypotonia
• Muscle cramps
• Muscle stiffness
Why make a diagnosis
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Parental request
Disease specific treatment
Disease specific complications
Prognostication
Genetic counselling
Antenatal diagnosis
History
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Presenting complaints
Onset
Progression
Developmental milestones
Systems inquiry
Family history
Clinical examinationestablishing the phenotype
• ptosis/opthalmoplegia/facial weakness/tongue
fasiculation
• Muscle size
• Hypotonia/myotonia
• Functional strength
• Muscle weakness prox vs distal, arms vs legs,
axial
• Contractures-limbs/spine
• Resp pattern
Where is the lesion
Muscle
bulk
Tone
Strength DT
R
UMN
N

N
Ant
horn
cell
Prox
wasting

P
nerve
Distal
wasting
NMJ
N
Muscle selectiv
e
Plan sensation
tars
fasicualti
on


N
-
Prox
weakne
ss


N
+

Distal
weakne
ss
Dis 
tal


rarely
N
fatigues N

N
-
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N
-

Investigations
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Blood
Radiological
Neurophysiological
Other
Floppy infant
• Looks floppy
• Feels floppy
• Increased joint
mobility
Hypotonia
• With weakness
– Neuromuscular
disorders
• Without weakness
– CNS
– Metabolic
– Chromosomal
– Connective tissue
Hypotonia
• With weakness
– Neuromuscular
disorders
• SMA
• Congenital myotonic
dystrophy
• Myotubular myopathy
• Congenital muscular
dystrophy
• Without weakness
– CNS
• Birth asphyxia/hypoxia
• CNS malformations
– Metabolic
• Lipidoses/mucopolysacch
aridoses
• Amino/organic acidurias
– Chromosomal
• Down syndrome
• Prader-Willi syndrome
– Connective tissue
• Ehlers Danlos/Marfans
• Osteogenesis Imperfecta
? When do we think of SMA?
• Child with hypotonia and weakness
• The weakness is usually symmetrical and
more proximal than distal.
• Sensation is preserved.
• Weakness in the legs is greater than in the
arms.
• Severity of weakness generally correlates
with the age of onset
Clinical Spectrum
Type I
Type II
Type III
Werdnig Hoffman
Sit unaided, not
standing
Independent
walking with
proximal weakness
Hypotonia /floppy
weakness/wasting
breathing / feeding
difficulties
Absent reflexes
Tremor affecting
upper limbs
Prognosis
dependent on chest
Death < 2 years
6 months
18 months
Age at Presentation
5 years
Genetics
• Autosomal recessive
• Carrier frequency 1 in 40 in general population
• Due to loss of function of SMN1 (survival motor neurone
1)
• Gene located on Cr 5 is the Survival Motor Neurone
gene
• SMN gene has 9 exons & encodes a protein found in all
cells but most abundantly in the nucleus of the motor
nerve
• 93% of patients with SMA are missing exon 7 in both
copies of the SMN gene.
Duchenne muscular dystrophy
Clinical presentation
• Age within first 5 years of age
• Delayed motor milestones esp walking
– 50% 18 months
– 25% 2 years
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Abnormal gait ( toe walking, waddling)
Frequent falls
Other motor difficulties
Speech and language delay
Global delay
Gowers manoeuvre
Cardinal clinical signs
• Broad based waddling gait, lordotic
posture
• Inability to run,jump or hop normally
• Positive Gowers
• Prox musc weakness legs> arms
• Prominence of calves
• 1:3500 births
• X linked recessive; mutation in dystrophin gene
located at Xp21
• Diagnosis
– Clinical assessment
– Molecular genetic testing
• Picks up 60-65% deletions
• Duplications in 5-15%
• Rest point mutations/intronic rearrangements
– Dystrophin expression on muscle biopsy
What is a neuropathy
• Disease in which the peripheral nerve is
damaged
• Acquired or genetic
• Axonal or demyelinating
• Polyneuropathy,focal or multifocal
• Motor,sensory,sensorimotor or autonomic
HMSN type 1
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Slowly progressive distal neuropathy
Onset childhood-adulthood
Progressive distal atrophy and weakness
Pes cavus
Sensory loss later
Motor and sensory conduction very slow
• AD
• 1A duplication/point mutation of PMP 22
gene on chromosome 17p11.2
• 1B: point mutation of protein zero gene on
1q22
• More loci as well
Summary
• Think about where lesion is likely to be
based on history and examination
• THEN make appropriate investigations
Any questions???