Orthopaedic Syndromes: An Overview

1. Syndromes of Orthopaedic Importance Meghan Imrie, MD Core Course Curriculum January 27, 2016

2. Syndromes overview • “orthopaedic importance” • What ABOS/AAOS/POSNA expects you to know • What the patient’s parent in peds clinic that day wants you to know • What you actually need to know for practice

3. Syndromes Overview • Looked through OITE from 2005-2010 • Ordered the syndromes by frequency of testing during that time • NOT complete review of syndromes • “knee jerk” approach - what you need to know for testing

4. Syndromes overview • A few practical tips • Take close family history • Make an excuse to leave the room and consult book or internet • Re-evaluate patient for further features learned from above • If any question, call or refer to genetics

5. Based on 2005-2010 OITEs: Osteogenesis imperfecta Neurofibromatosis Charcot Marie Tooth Arthrogryposis Myelomeningocele Marfan’s Down’s Prader-Willi Beckwith-Wiedemann Ehler’s Danlos Gaucher’s Osteopetrosis Duchenne’s MD Will also discuss MPSs Loeys-Dietz Rett’s Syndromes overview

6. Osteogenesis Imperfecta • Technically, a metabolic/endocrine bone disease • Genetic disorder of connective tissue leading to increased bone fragility • Wide clinical variation • >90% have identifiable, genetically determined qualitative and/or quantitative defect in type I collagen • Skin test vs DNA blood test • Still, clinical diagnosis

7. Osteogenesis Imperfecta • Pathophysiology • (forgive the simplification, Lane!) • Type I collagen • major structural connective tissue protein of skeletal system • Composed of 3 strands of collagen protein • 2 alpha 1 strands and 1 alpha 2 strand • COL1A1 encodes pro-alpha 1; COL1A2 encodes pro-alpha 2 • Quantitative defect: often heterozygous with one copy not producing any • Qualitative defect: error in substitution or deletion leading to abnormal, less effectual collagen

8. Osteogenesis Imperfecta • Wide clinical variation • Non-accidental trauma vs fracture from mild OI • Difficult distinction if no family history, blue sclerae, etc • Involve CPS if any question • With increased genetic knowledge, classification increasingly difficult/muddled • Some thought to simplified phenotypic classification: mild, moderate, severe, lethal • Sillence classification • Most commonly used

9. Osteogenesis Imperfecta

10. Osteogenesis Imperfecta • General treatment principles • Bones heal fairly predictably, but do not remodel reliably • Our usual “as long as they are in the same room” kid rules therefore don’t always apply • Under age 2, can usually treat more or less regularly • For minimally displaced,angulated fractures, immobilize for as short a duration as possible • Until child no longer symptomatic • To prevent further osteopenia/fracture risk • Don’t use plates • Intramedullary devices best • Rush rods, telescoping rods

11. Osteogenesis Imperfecta • Sofield osteotomies • For deformed long bones • Indications fairly varied • “shish-kebob” osteotomy • Stabilize with rush rod or telescoping rod (Bailey-Dubow, Fassier-Duval) • Scoliosis • Not uncommon • Bracing not usually used due to risk of rib deformity • Challenging surgically • Usually for curves >50 or 60 degrees

12. Osteogenesis Imperfecta - Sofield osteotomy

13. Osteogenesis Imperfecta - Sofield osteotomy

14. Osteogenesis Imperfecta - Sofield osteotomy

15. Osteogenesis Imperfecta - Sofield osteotomy

16. Basilar impression/invagination Due to soft bone of foramen magnum/microfractures of skull base Leads to direct brainstem compression Most common in type IVB Sxs: headache, dysarthria, dysphagia, spasticity, increasing contractures Plain films not very helpful Need 3-D imaging (MRI probably best) Rx: often, anterior decompression/PSF (neurosurg) Bisphosphonate use in OI Depending on area of practice, still controversial IV pamidronate currently “gold standard” Numerous studies show increase in BMD by DEXA (?clinical implication?) Some studies report Decreased fxs Decreased pain Better mobility Increased height Placebo trial vs po alendronate: no change in fx rate Bottom (biased) line: don’t forget the half-life of these meds… OI - possibly tested material

17. OI - summary • “brittle bone” disease • Due to quantitative and/or qualitative defects in type I collagen • COL1A1 and COL1A2 culprits • Varied clinical spectrum • Mild OI and NAT can be difficult to distinguish • Olecranon fracture in adolescent on OITE = probably has OI • Usual peds fracture principles don’t necessarily apply • Remodeling unpredictable • Don’t plate • Sofield osteotomy work horse for deformities • Be on look out for basilar invagination (especially in adults) • Bisphosphonates may be tested: pamidronate gold standard, increase DEXA definitely, probably reduce fracture rate and pain • But we don’t currently recommend them…

18. Based on 2005-2010 OITEs: Osteogenesis imperfecta Neurofibromatosis Charcot Marie Tooth Arthrogryposis Myelomeningocele Marfan’s Down’s Prader-Willi Beckwith-Wiedemann Ehler’s Danlos Gaucher’s Osteopetrosis Duchenne’s MD Will also discuss MPSs Loeys-Dietz Rett’s Syndromes overview

19. Neurofibromatosis • Hereditary, AD, hamartomatous disorder affecting: • Central nervous system • Peripheral nervous system • Skeleton • Skin • Deeper soft tissues • 50% spontaneous mutation • Two types: • NF-1: aka von Recklinghausen’s disease • Defect on chromosome 17 • NF-1 gene encodes neurofibromin protein • Tumor suppressor gene --> key protein in cell growth and differentiation • Peripheral NF • NF-2: bilateral acoustic NF • Defect on chromosome 22 • Central NF • Rare orthopaedic manifestations

20. Neurofibromatosis • NIH diagnostic criteria for NF 1 = need >2 • More than six café au lait spots, at least 15 mm in greatest diameter in adults and 5 mm in children • Two or more neurofibromas of any type or one plexiform neurofibroma • Freckling in the axillae or inguinal regions (Crowe's sign) • Optic glioma • Two or more Lisch nodules (iris hamartomas) = pathognomonic • A distinctive bone lesion, such as sphenoid dysplasia or thinning of the cortex of a long bone, with or without pseudarthrosis • A first-degree relative (parent, sibling, or offspring) with neurofibromatosis type 1 by these criteria

21. Neurofibromatosis • MSK manifestations • Less than 10% of NF 1 patients req ortho mgmt • Tibial bowing and pseudarthrosis • Scoliosis • Hemihypertrophy • Other sites of “dumb” bone • forearm

22. Neurofibromatosis • Tibial issues • AnteroLateral bowing • AL = café Au Lait spots (don’t laugh, my brain is small) • Management • Try to prevent fracture • Clamshell orthosis • Do not operate if not broken! • If it breaks • No bueno :( • Hope you like the family… • Some peds ortho MDs using BMP in this situation • When all else fails, Symes

23. Neurofibromatosis • Scoliosis - most common MSK • Rates 10-60% of NF pts • Dystrophic vs non-dystrophic • Important distinction as natural history very different • Dystrophic • Characterized by: • Short, sharp curve • Vertebral scalloping • Enlarged foramina • Pencilling of ribs (> 3, 87% risk of progression) • Kyphotic • Non-op (ie brace) rx not effective • Get an MRI pre-op • A/PSF recommended due to high pseudoarthrosis rate with posterior only • Non-dystrophic • Behaves like IS • But can switch to dystrophic type

24. Neurofibromatosis • Hemihypertrophy • Rare • Debulking unsatisfactory • Try epiphysiodesis for LLD • Other areas of “dumb” bone • Forearm • Has been tested on OITE (on diagnosis, not on treatment)

25. Neurofibromatosis - summary • AD disease of CNS, PNS, skin, skeleton • Café au lait spots: Coast of California • NF 1 (chromosome 17, neurofibromin protein) has MSK manifestations • Most common genetic disorder caused by mutation in single gene • Dumb bone problems • Anterolateral tibial bowing: prevent fracture, don’t do osteotomy! • Scoliosis: dystrophic curves worse, need MRI and A/PSF • Dumb bone can be anywhere • Forearm seems favored by OITE

26. Based on 2005-2010 OITEs: Osteogenesis imperfecta Neurofibromatosis Charcot Marie Tooth Arthrogryposis Myelomeningocele Marfan’s Down’s Prader-Willi Beckwith-Wiedemann Ehler’s Danlos Gaucher’s Osteopetrosis Duchenne’s MD Will also discuss MPSs Loeys-Dietz Rett’s Syndromes overview

27. Charcot Marie Tooth Disease • One of hereditary motor sensory neuropathies (HMSN) • Motor sensory demyelinating or axonal neuropathy • But motor much more involved than sensory • 2 main types with two more recent forms identified • CMT 1: • manifests earlier • AD • More common • CMT 2: • manifests in 3rd decade • AD or AR • DTRs preserved • CMTX: • Second most common form • X-linked dominant • Orthopaedic manifestations similar

28. Charcot Marie Tooth • Diagnosis confirmed by DNA testing • Numerous genetic abnormalities • CMT 1: duplication in chr 17, coding for peripheral myelin protein 22 (PMP 22) • CMT X (x-linked CMT): mutations in connexin32 gene • Little correlation between genotype and phenotype

29. Charcot Marie Tooth • Orthopaedic manifestations: • Feet • Cavovarus • Hip • Late dysplasia • Spine • Scoliosis (with kyphosis) • Hand • Intrinsic weakness with clawing

30. Charcot Marie Tooth • Cavovarus foot • From various muscle imbalances • Intrinsic muscle wasting --> clawing of toes, contracture of plantar fascia • Anterior tib and peroneus brevis weaken before peroneus longus and posterior tib --> cavovarus

31. Charcot Marie Tooth - foot • Peroneus longus + posterior tib > peroneus brevis + anterior tib • Plantarflexion of first ray --> • Heel varus • Initially flexible • Then becomes fixed

32. Charcot Marie Tooth - foot • Coleman block test • Tests flexibility of hind foot • Allows first ray to drop down • If hindfoot corrects to valgus • Soft tissue +/- first ray osteotomy only • Peroneal longus transfer to brevis, post tib to dorsum of foot, plantar fascia release • If hindfoot doesn’t correct • Have to do calcaneal osteotomy or fusion

33. Charcot Marie Tooth - summary • Diagnosis confirmed with DNA test • CMT 1: chr 17, PMP 22 • CMT X: x linked, connexin • Ortho manifestations • Feet • Cavovarus since peroneus longus stays stronger longer than anterior tib • If flexible (heel corrects on Coleman block), no calcaneal osteotomy or triple needed • Hip: Late dysplasia • Hand: Intrinsic wasting • Spine: scoliosis

34. Based on 2005-2010 OITEs: Osteogenesis imperfecta Neurofibromatosis Charcot Marie Tooth Arthrogryposis Myelomeningocele Marfan’s Down’s Prader-Willi Beckwith-Wiedemann Ehler’s Danlos Gaucher’s Osteopetrosis Duchenne’s MD Will also discuss MPSs Loeys-Dietz Rett’s Syndromes overview

35. Arthrogryposis • Term used for variety of conditions characterized by: • Decreased fetal movement • Congenital joint stiffness • Varying muscle weakness • Amyoplasia, distal arthrogryposis, multiple pterygium syndrome, Larsen’s (flattened facies, multiple joint dislocations, cervical kyphosis, watch for late myelopathy) • Symptom complex rather than disease • AMC (arthrogryposis multiplex congenita, aka amyoplasia) • Decrease in anterior horn cells • Normal intelligence • Sensation intact

36. Arthrogryposis - amyoplasia • Common deformities • Hip: • Considered teratologic, so Pavlik not indicated • Previous controversy about relocation • Most authors now recommend medial open reduction as infant (older tests, especially if detected in older patient, recommend obs) • Knee: • Flexion or extension contractures • Correct knees before hips if ext • Flexion deformities tend to recur over time despite rx

37. Arthrogryposis - amyoplasia • Common deformities cont’d • Foot • Rigid clubfoot or vertical talus • For TEV, some authors report success with Ponseti method (prob won’t be tested) • Treat initially with PMR • Recurrence common • Treat with bony procedure like talectomy or triple arthrodesis • CVT requires surgery • Spine • Often C shaped, neuromuscular-esque • Bracing ineffective

38. Based on 2005-2010 OITEs: Osteogenesis imperfecta Neurofibromatosis Charcot Marie Tooth Arthrogryposis Myelomeningocele Marfan’s Down’s Prader-Willi Beckwith-Wiedemann Ehler’s Danlos Gaucher’s Osteopetrosis Duchenne’s MD Will also discuss MPSs Loeys-Dietz Rett’s Syndromes overview

39. Myelomeningocele • Aka spina bifida • Failure of neural tube to close • Type of spinal dysraphism • Vs caudal regression (sacral agenesis) • Maternal diabetes • Functional level = lowest functioning nerve root • L4 key level (ambulatory potential): why? • Can diagnosed prenatally • Ultrasound • Maternal serum alpha fetal protein (if levels detectable after week 14) • Common comorbidities - kids benefit from multi-disciplinary team • Arnold-Chiari malformation type II • Bowel/bladder control issues • Latex sensitivity/allergy (may present as anaphylaxis in OR on test)

40. Myelomeningocele • Incidence decreasing • Prenatal screening • Recognition of role of folic acid • Why your Cheerios are fortified • Most studies quote 60-100% reduction in incidence when pregnant women given folate • USDA rec: 0.4 mg/day

41. Myelomeningocele • Detailed exam important at each visit • Looking for change in function • Increased UTIs • Loss of level (muscle testing) or function • Increased spasticity • Sudden increase in spine curve • Get MRI of entire spine (including lower brain stem) if any of above • Likely increased hydrocephalus • Vs tethered cord or hydromyelia • Fractures • Fairly common, especially ages 3-7 about knee and hip • Present like infection: red, warm, swollen • Rarely infection, but can be (probably won’t be on test) • Treat with brief immobilization

42. Myelomeningocele - ortho issues • Spine • Scoliosis and kyphosis • Neuromuscular curve • Thoracic level myelos most frequent • Bracing not effective • Need anterior and posterior fusion • Why? • For kyphosis, may need kyphectomy • High complication rate • Pseudoarthrosis • Infection: 15-25%

43. Myelomeningocele - ortho issues • Hips • Problems include • Flexion contractures (thoracic and high lumbar) • Muscle/capsular release • Abduction contracture • Ober-Yount release • Adduction contracture • Adductor release • Paralytic hip dislocation • Most likely at L3/L4 level: why? • Previously controversial • Now most authors agree to leave them out (good TSRH gait study) • Exception: very low level sacral pt, otherwise normal

44. Myelomeningocele - ortho issues • Knee • Flexion or extension deformity depending on level • Soft tissue release as needed for functional gains • Feet • Deformity depends on level • Rigid clubfeet, vertical talus, calcaneus feet • Likely level that, if functioning, is cutoff between equinus vs calcaneus deformity? (in reality, not this simple) • L5 • Soft tissue releases/tendon transfers • Avoid triple arthrodesis except in severe deformities in sensate feet

45. Myelomeningocele - summary • Folic acid prevention • Sacral agenesis (on same spectrum): maternal diabetes • Latex allergy = anaphylaxis (crashing patient) in surgery • Change in function/scoli curve --> get MRI of entire spine --> increased hydrocephalus (no bueno, call neurosurg) or tethered cord • Non-op limb that looks like it might have osteo = likely fracture • Scoli surgery = go anterior and posterior • Leave dislocated hips out (unless patient looks totally normal and you are told has sacral myelo)

46. Based on 2005-2010 OITEs: Osteogenesis imperfecta Neurofibromatosis Charcot Marie Tooth Arthrogryposis Myelomeningocele Marfan’s Down’s Prader-Willi Beckwith-Wiedemann Ehler’s Danlos Gaucher’s Osteopetrosis Duchenne’s MD Will also discuss MPSs Loeys-Dietz Rett’s Syndromes overview

47. Marfan’s syndrome • Clinically diverse group • Very tall • Long, thin limbs • Long, thin fingers • Ocular lens dislocation • Cardiac anomalies • Autosomal dominant • Spontaneous mutation 15-30% of time • Defect in fibrillin • No good genetic test • Diagnosis made by Ghent criteria • Sponseller et al, JBJS 2010

48. Marfan’s syndrome • Orthopaedic manifestations • Spine: Ghent criteria • scoliosis • 50% of patients • Bracing usually not effective • Spondylolisthesis • Can have dural ectasia and meningocele (like NF) • Hips: • Significant acetabular protrusio • Can cause pain and stiffness • Generalized joint laxity • Genu recurvatum • Severe pes planus • Stick with non-op rx

49. Based on 2005-2010 OITEs: Osteogenesis imperfecta Neurofibromatosis Charcot Marie Tooth Arthrogryposis Myelomeningocele Marfan’s Down’s Prader-Willi Beckwith-Wiedemann Ehler’s Danlos Gaucher’s Osteopetrosis Duchenne’s MD Will also discuss MPSs Loeys-Dietz Rett’s Syndromes overview

50. Down’s syndrome • Trisomy 21 • Most common chromosomal abnormality • Incidence increases with increasing maternal age • Boo • Very typical facies, hypoplastic middle phalanx of 5th finger • Associated with • Heart disease • Mental retardation • Endocrine disorders • Hypothyroidism • Diabetes • Premature aging