Orthopaedic conditions in RAS/ Mapk family disorders

1. Orthopaedic conditions in RAS/Mapk family disorders Kent Reinker, MD Clinical Professor U. Texas, San Antonio

2. What’s to be covered? • Diagnosis • Lower Extremity • Upper Extremity • Spine • Generalized

3. We will draw heavily from • Orthopaedic Conditions in Ras/MAPK Related Disorders, Reinker, Stevenson, Tsung, J PediatrOrthop. 2011:599-605. • Costello syndrome: orthopaedic manifestations and functional health,Yassir, Grottkau, Goldberg. J PediatrOrthop. 2003 Jan-Feb;23(1):94-8

4. Diagnosis • RAS/MAPK disorders overlap • Phenotypic overlap • Growth delay • Hypotonia • Cardiac Anomaly • Characteristic facies

5. Diagnosis • RAS/MAPK disorders overlap • Genotype overlap • Noonan Genotype • PTPN, SOS1, KRAS, NRAS, RAF1, BRAF, MEK1, SHOC2, CBL, Unknown • CFC Genotype • BRAF, MEK1, MEK2, KRAS, Unknown • Costello Genotype • HRAS, Unknown • Leopard Genotype • PTPN, RAF1

6. Costello Syndrome – Goldberg, JPO 23:94-8,2003 • 18 Patients • 16 Short, broad hyperextensible digit • Wrists & elbows flexed to 90 degrees • 10 Decreased elbow ROM • 13 Tight heel cords • 5 Vertical talus • 7 Planovalgus • 6 Overriding 2nd toes • 4 Metatarsus adductus

7. Costello Syndrome-Goldberg • 3 Plantar flexed great toe • 3 Hip subluxations • 3 Kyphosis • 3 Scoliosis • 1 Radial head subluxation • 1 Pectusexcavatum

8. Methods • We examined patients at the last combined meeting of the Costello, CFC, and Noonan Societies and combined these with a number of patients previously known by the authors

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16. New findings - Stevenson • Decreased bone density is found in many patients with MAPK disorders • Metabolic bone disorder? • Disuse? • Decreased grip strength is found in many patients with MAPK disorders • Myopathy?

17. Discussion • Orthopaedic disorders in MAPK syndromes come in 3 flavors • Intrinsic to the disorder • Secondary to something else • Unrelated • Probably the most common • MAPK disorders do not immunize patients against other medical problems

18. Discussion • Treatment of these disorders should take into account the syndrome • What’s the pathophysiology? • Encephalopathy, myopathy, neuropathy? • Is treatment likely to be complicated by other things going on? • Clotting disorders, spinal cord anomaly, myopathy?

19. Discussion • Few orthopaedic surgeons are likely to be familiar with these syndromes • You may need to help them

20. Discussion • A few disorders of special interest • Spinal Cord abnormalities • High number of these in Noonan, CFC, and Costello • Need to look for them with neurologic exam and MRI

21. Discussion • Disorders of special interest • Pain syndromes in Noonan adults • Common & puzzling • Neuropathy? • Spinal cord anomaly? • Bone turnover?

22. Disorders of special interest • Scoliosis surgery • Workup should include: • Spinal MRI • Neck x-rays • Clotting studies in Noonan • Anesthesiologistready for hyperthermia

23. Disorders of special interest • Hand anomaly in Costello • Unique • Treatment?

24. Thanks for your attention