1. Hypotonia, neuropathies and myopathies

2. 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

3. Reasons for referral Delay in motor milestones Abnormal gait
Tendancy to fall
Overt muscle weakness, floppiness or hypotonia
Muscle cramps
Muscle stiffness

4. Why make a diagnosis Parental request Disease specific treatment
Disease specific complications
Prognostication
Genetic counselling
Antenatal diagnosis

5. History Presenting complaints Onset Progression
Developmental milestones
Systems inquiry
Family history

6. Clinical examination- establishing 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
Muscle enlargement/atrophy

7. Where is the lesion Muscle bulk Tone Strength DTR Plantars sensation
fasicualtion
UMN N  -
Ant horn cell
Prox wasting 
Prox
weakness  +
P nerve
Distal wasting
Distal weakness
Distal 
rarely
NMJ
fatigues
N- 
selective

8. Investigations Blood Radiological Neurophysiological Other
CK elevated in
Musc dystrophies, metabolic and inflamm myopathies, carriers of DMD, hypothyroidism,hyperCKaemia,malignant hyperthermia, healthy individuals after excessive exercise
Myasthaenia=tensilon
Skeletal-xray hips/spine
Resp
Cardiac
swallow

9. Floppy infant
Looks floppy
Feels floppy
Increased joint mobility

10. Hypotonia With weakness Without weakness Neuromuscular disorders CNS
Metabolic
Chromosomal
Connective tissue
How can you tell whether weak= antigravity mvmts, resistance on pull to sit

11. Hypotonia With weakness Without weakness Neuromuscular disorders CNS
SMA
Congenital myotonic dystrophy
Myotubular myopathy
Congenital muscular dystrophy
Without weakness
CNS
Birth asphyxia/hypoxia
CNS malformations
Metabolic
Lipidoses/mucopolysaccharidoses
Amino/organic acidurias
Chromosomal
Down syndrome
Prader-Willi syndrome
Connective tissue
Ehlers Danlos/Marfans
Osteogenesis Imperfecta
How can you tell whether weak= antigravity mvmts, resistance on pull to sit

12. ? 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
The most severe type presents in
infancy. The infant may appear normal at birth. Weakness
evolves within the first few months of life. Occasionally,
decreased intrauterine movements suggest prenatal onset of
the disease and present with severe weakness and joint contractures
at birth.6 Milder types of spinal muscular atrophy
present with later onset, and the course is more insidious.
Some children sit but never walk, whereas others show
delayed walking but may be able to maintain walking until
adult years. For the purpose of clinical care and discussion,
individuals manifesting different levels of weakness
due to spinal muscular atrophy have been divided into 4
groups defined by functional ability

13. Clinical Spectrum Type I Type II Type III 6 months 18 months 5 years
Werdnig Hoffman
Hypotonia /floppy weakness/wasting breathing / feeding difficulties
Absent reflexes
Death < 2 years
Type II
Sit unaided, not standing
Tremor affecting upper limbs
Prognosis dependent on chest
Type III
Independent walking with proximal weakness
6 months months years
Age at Presentation

14. 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.
A further 5% are missing exon 7 in one copy and have a rearrangement in the other copy
2% have rearrangements and will not be picked up on routine genetic testing
SMN2 produces only 10% full length SMN protein
predicting clinical phenotype using SMN2 copy number can be risky and is not currently recommended. Cannot easily determine smn 2 copy number

15. Duchenne muscular dystrophy

16. Clinical presentation
Age within first 5 years of age
Delayed motor milestones esp walking
50% 18 months
25% 2 years
Abnormal gait ( toe walking, waddling)
Frequent falls
Other motor difficulties
Speech and language delay
Global delay

17. Gowers manoeuvre

18. 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

19. X linked recessive; mutation in dystrophin gene located at Xp21
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

20. 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

21. HMSN type 1

22. Slowly progressive distal neuropathy
Onset childhood-adulthood
Progressive distal atrophy and weakness
Pes cavus
Sensory loss later
Motor and sensory conduction very slow

23. 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

24. Summary
Think about where lesion is likely to be based on history and examination
THEN make appropriate investigations

25. Any questions???