1. Paediatric Neuromuscular Disease Recent Advances in Neuromuscular Disease VS What is old in neuromuscular disease (and should be remembered)

2. Neuromuscular Disease Insist on accurate terminology

3. Changing Diagnosis Patient RT 1 2 3 4

4. Neuromuscular Disease Traditional symptoms and signs • Muscle weakness • Muscle wasting • Hypotonia • Hyporeflexia • Sensory disturbance

5. Neuromuscular Disease Muscle weakness is not a complaint of childhood My deltoids are about MRC 4/5

6. Neuromuscular Disease Parental concerns 20 ambulant children with weakness • Trouble walking and running • Poor at sports • Cannot keep up with peers • Poor coordination • Tires easily • Falls frequently

7. Neuromuscular Disease Some atypical presentations • Behaviour disorder (dermatomyositis) • Delayed intellectual or language development (DMD) • Dysmorphic features : high palate, micrognathia,UDT, • Arthrogryposis (foetal akinesia deformation syndrome) • Feeding difficulty, pharyngeal incoordination • Leucodystrophy (congenital musc dystrophy) • Vocal cord palsy at birth (SMA) • Constipation (myotonic dystrophy) • Elevated aminotransaminases (dystrophies)

8. Neuromuscular Disease Read between the lines

9. Neuromuscular Disease Patient JF - medical record notes Visit - 1 22/12 5 year old male - prep grade “Cannot run as fast as classmates” “Always falling over” “Teacher has recommended a check to see why he cannot run fast” O/E: Gait - prominent lumbar lordosis - broad based Imp: No serious abnormality - seems to be an awkward clumsy child

10. Neuromuscular Disease Patient JF - medical record notes Visit - 2 2/2 “Noticed by teachers to be not running properly” O/E: “Pleasant boy with rolling gait with pelvis tending to drop to right” “Right quads slightly wasted” “Tone, power, reflexes normal” Plan: “X-ray hips. Refer to Orthopaedic clinic” 19/2 Orthopaedic and Neurology Clinics Classical Duchenne Can barely walk up steps or rise from floor

11. Duchenne Muscular Dystrophy Presentation • Known family history • Delayed motor milestones • Gait disturbance • Delayed mental development • Delayed language development

12. Duchenne Muscular Dystrophy Age at walking - 111 patients number of patients months

13. Duchenne Muscular Dystrophy Indications for CK (In relation to muscular dystrophy) • Known or suspected family history • Unexplained delay in motor development • Especially male not walking by 18 months • Unexplained gait disturbance - esp. toe walking • Unexplained intellectual impairment • Unexplained language delay

14. Neuromuscular Disease Do not expect classic adult features in children

15. Peroneal Muscular Atrophy Hallmarks of peroneal muscular atrophy Tooth (1886) • Commences in lower extremities • Hands and forearms attacked early • Disease is one of childhood • Heredity is a marked feature • Fibrillar or fascicular tremors are frequent • Degenerative electrical changes often seen early • Disease of peripheral nerves

16. Peroneal Muscular Atrophy Age at onset Harding / Thomas Brain 103:259 1980

17. Peroneal Muscular Atrophy Age at onset of symptoms RCH - 42 children

18. Peroneal Muscular Atrophy Champagne bottle legs

19. Peroneal Muscular Atrophy Symptoms / signs at presentation RCH - 44 patients (types 1 & 2)

20. Peroneal Muscular Atrophy Brothers with PMA type 1

21. Neuromuscular Disease Affected parents may be asymptomatic

22. Peroneal Muscular Atrophy Patient HR (1) 34 years. Asymptomatic 5 years age. Poor coordination, frequent falls, no foot deformity

23. Peroneal Muscular Atrophy Patient HR (2) 34 years. Asymptomatic 5 years age. Poor coordination, frequent falls, no foot deformity

24. Peroneal Muscular Atrophy Asymptomatic parents Vanasse et al 1981 • 11 affected parents • 4 definite symptoms • 2 minimal deficit on examination • 5 asymptomatic / normal examination • RCH Series • 7 out of 40 affected parents asymptomatic

25. Congenital Myotonic Dystrophy Asymptomatic parents Harper 1975 • 54 mothers of CMyoD children • asymptomatic at time of diagnosis 20 • symptomatic - no medical attention 14

26. Neuromuscular Disease Ask for old photographs

27. Congenital Myotonic Dystrophy Patient JS (centre)

28. Neuromuscular Disease Review old biopsies and postmortems

29. Neuromuscular Disease Review old material / ask for photographs

30. Neuromuscular Disease Review undiagnosed patients changing signs improved knowledge new diagnostic tests

31. Emery Dreifuss Dystrophy Patient AB

32. Neuromuscular Disease Do not always accept what parents tell you

33. Neuromuscular Disease Patient CN Father of BN

34. Neuromuscular Disease Patient BN Daughter of CN

35. Neuromuscular Disease If you think you are onto a good thing stick to it

36. Tomaculous Neuropathy (HNPP) Patient SW 12y Acute onset brachial palsy while swimming

37. Tomaculous Neuropathy (HNPP) Family of SW 1 2 3 4 Brachial plexus palsy 4 3 Ulnar palsy 2Four focal neuropathies 1Transient foot drop

38. Tomaculous Neuropathy (HNPP) Pathology

39. Tomaculous Neuropathy (HNPP) Cardinal Features • Recurrent mononeuropathies or plexopathies • NCS abnormalities in clinically unaffected nerves • Characteristic pathology - myelin thickenings • Autosomal dominant inheritance • DNA deletion 17p 11.2 (PMP-22 gene)

40. Tomaculous Neuropathy (HNPP) Clinical • Incidence: 16 / 100,000 population (?higher) • Onset: 50% in second decade (birth - old age) • Problem: Initial mononeuropathy (or plexopathy) • Deficit: Motor > sensory. Painless • Recover: Days to weeks • Note: Clinical heterogeneity. Many asymptomatic Some: tingling, cramps, myalgia, pes cavus

41. Tomaculous Neuropathy (HNPP) Clinical Sites involved • Nerves subject to compression, stretch, friction • Usually associated with trivial trauma • Commonest sites • peroneal at fibula head • ulnar at elbow • radial at spiral groove of humerus • median at carpal tunnel • brachial plexus, sciatic, cranial

42. Neuromuscular Disease Remember : You may be dealing with an iceberg The most dangerous bit is not obvious

43. Neuromuscular Disease Family H (1)

44. Neuromuscular Disease Family H (2)

45. Neuromuscular Disease Family H (3)

46. Neuromuscular Disease Family H (4) Anaesthetic related deaths 15 others positive for MH by CK or biopsy (2000)

47. Neuromuscular Disease Patient MB (female) 5m Delayed development, hypotonia Dysmorphic features - ptosis, abnormal ears, small - antimongoloid slant to eyes 4y Muscle biopsy (needle) - non specific / neurogenic 12y Scoliosis. CK 2243 (rr<240). Review of biopsy 16y Scoliosis surgery. Subtle MH reaction In vitro testing for MH - positive Diagnosis: King-Denborough syndrome

48. Neuromuscular Disease Patient MB

49. King-Denborough Syndrome J Pediatrics 83:37 1973 • Small build • Cryptorchidism • Pectus carinatum • Kyphosis / lordosis • Hypoplastic mandible • Crowded lower teeth • Antimongoloid slant to eyes • Ptosis • Low attachment of ears • Webbed neck

50. King-Denborough Syndrome