9
Pediatric Orthopaedic Surgery
Embryology: Key Points
Week 3
| 1. | At week 3, mesoderm gives rise to what? | 1. | Somites |
| 2. | Somites are responsible for the ________ skeleton? | 2. | Axial |
| 3. | Somites differentiate into what two parts? What does each form? | 3. | Dermomyotome (dermis, muscle) Sclerotome (vertebral column) |
| 4. | Dermomyotome differentiates into what two parts? What does each form? | 4. | Epimere (dorsal muscle) Hypomere (ventral muscle: abdomen, thorax) |
| 5. | Notochordal tissue eventually disappears, but, while present, induces formation of what? | 5. | The vertebral column |
| 6. | What remnant of notochord remains? | 6. | Nucleus pulposus |
Week 4
| 7. | Ectoderm and mesoderm interact to form what? | 7. | Apical ectodermal ridge |
| 8. | The apical ectodermal ridge is responsible for the ________ skeleton? | 8. | Appendicular |
| 9. | What does the apical ectodermal ridge control? | 9. | Proximal to distal development Mediates interdigital necrosis |
| 10. | This process is inhibited by what pharmacologic agent? What is the associated defect? | 10. | Thalidomide Phocomelia |
| 11. | What two genes regulate limb formation? | 11. | Homeobox Sonic hedgehog |
| 12. | What does the zone of polarizing activity (ZPA) control? | 12. | Anteroposterior (AP) axis of the limb |
| 13. | What does the Wnt (wingless) signaling center control? | 13. | Dorsoventral development of the limb |
| 14. | From what do limb muscles develop? | 14. | Limb bud mesenchyme |
Neural Crest Cells
| 15. | Neural crest cells arise from what? | 15. | Ectoderm |
| 16. | Where do they start? Then what happens? | 16. | Start at margins of the neural tube Then they migrate with neural tube |
| 17. | What eight structures do they form? | 17. | Spinal cord Pharyngeal arches Dorsal root ganglion (DRG) Peripheral sensory nerves Adrenal medulla Sympathetic chain Schwann cells Melanocytes |
Key Lists of Structures and Origins
| 18. | What three structures does ectoderm form? | 18. | Skin Nervous system Neural crest cells |
| 19. | What does mesoderm form? | 19. | Connective tissues |
| 20. | What are three examples of connective tissue? | 20. | Bone Muscle Blood |
| 21. | What three entities does endoderm form? | 21. | Lung Gut lining Associated organs |
Cervical Spine Development
Atlas Development
| 22. | From how many ossification centers does the atlas form? | 22. | Three |
| 23. | What are they? | 23. | Anterior arch Two neural arches |
| 24. | When do the two neural arches fuse posteriorly? | 24. | At age 3 to 4 years |
| 25. | When does the anterior arch fuse to the posterior arch? at what location? | 25. | At age 7 years Neurocentral synchondrosis |
Axis Development
| 26. | When does the odontoid process begin forming? From what? | 26. | In utero (by 7th month of gestation) From two separate ossification centers on either side of the midline |
| 27. | These longitudinal centers fuse at ________ months to form what? | 27. | 3 months to form chondrum terminale |
| 28. | How many total ossification centers are present in the axis at birth? | 28. | Four |
| 29. | What are they? | 29. | Odontoid process (from chondrum terminale) Body (centrum) Two neural arches |
| 30. | When do the neural arches fuse posteriorly to each other? | 30. | At age 2 to 3 years |
| 31. | When do the neural arches fuse to the body? | 31. | At age 3 to 6 years |
| 32. | What separates the body from odontoid process? | 32. | Dentocentral synchondrosis |
| 33. | How long might the dentrocentral synchondrosis persist? | 33. | May persist until age 11 years May be confused with a fracture |
| 34. | Chondrum terminale is what? | 34. | Secondary ossification center, which appears at the tip of the apex |
| 35. | The chondrum terminale ossifies at age 5 to 8 years to become what? | 35. | Ossiculum (os) terminale |
| 36. | When does it generally fuse to the remainder of the odontoid process? | 36. | At age 10 to 13 years |
Remainder of the Cervical Spine
| 37. | How many ossification centers are in each vertebral body? | 37. | Three |
| 38. | What are they? | 38. | Vertebral body Two neural arches |
| 39. | The neural arches fuse posteriorly to each other by what age? | 39. | 2 to 3 years |
| 40. | The vertebral body fuses with the neural arches by what age? | 40. | 8 years |
| 41. | What is the significance of this fusion? | 41. | Fixes canal diameter |
| 42. | 95% of canal diameter has been achieved by what age? | 42. | 5 years |
| 43. | Secondary ossification centers may resemble fractures at what three locations? | 43. | Tip of transverse process Tip of spinous process Superior/inferior aspects of the vertebral bodies |
Congenital Torticollis
| 44. | Congenital torticollis is commonly associated with what two conditions? | 44. | Hip dysplasia Metatarsus adductus |
| 45. | In these patients, what conditions must be excluded? | 45. | Atlanto-occipital abnormalities |
| 46. | What is the indication for surgery for congenital torticollis? | 46. | Persists for over 1 year despite therapy |
Other Common Embryology Questions and Review
| 47. | What does lateral plate mesoderm form? | 47. | Red blood cells |
| 48. | Vascular invasion and appearance of primary ossification centers occurs when? | 48. | At 8 weeks |
| 49. | Secondary ossification centers appear when? | 49. | At 39 weeks |
| 50. | What is the first ossification center to appear? | 50. | Distal femur |
What is the tissue of origin for the following glands:
| 51. | Parathyroid gland? | 51. | Third and fourth pharyngeal pouches |
| 52. | Thyroid gland? | 52. | Foramen cecum |
| 53. | Anterior pituitary gland? | 53. | Rathke’s pouch |
| 54. | Adrenal medulla? | 54. | Neural crest |
| 55. | Adrenal cortex? | 55. | Mesoderm |
| 56. | What adult structure is a remnant of the notochord? | 56. | Nucleus pulposus |
| 57. | From what do the trunk muscles arise? | 57. | Myotomes of somite |
| 58. | From what do the limb muscles arise? | 58. | Limb bud mesenchyme |
Review of Key Genetics Facts
| 59. | Classically, mendelian disorders are associated with how many genes? | 59. | One |
| 60. | What is the difference between triploidy and trisomy? | 60. | Triploidy means that all chromosomes are in triplicate, totaling 69 Trisomy means that one chromosome is in triplicate (e.g., as in Down syndrome) |
| 61. | What are two X-linked dominant disorders? | 61. | Hypophosphatemic rickets Pseudohypoparathyroidism |
| 62. | What are six X-linked recessive disorders? | 62. | Spondyloepiphyseal dysplasia tarda Hemophilia Hunter’s syndrome Duchenne’s muscular dystrophy Becker’s muscular dystrophy Menkes’ syndrome |
| 63. | What is the definition of genetic locus? | 63. | Position of the genes on chromosome |
Anticipation
| 64. | What is the definition of anticipation? | 64. | Increasing severity of disease with each generation |
| 65. | What is a disorder that displays anticipation? | 65. | Myotonic dystrophy |
| 66. | What is the mode of inheritance for this disorder? | 66. | Autosomal dominant (AD) |
| 67. | What genetic sequence is repeated? | 67. | CTG |
| 68. | What is the associated clinical problem? | 68. | Inability to relax muscle |
| 69. | What is genomic imprinting? | 69. | Clinical manifestation of disease depends on which parent has the mutation |
| 70. | What is a disorder that displays imprinting? | 70. | Prader-Willi (father) Angelman (mother) |
| 71. | What is germline mosaicism? | 71. | Only gonadal cells carry the mutation |
Disorders of the Growth Plate
Review of Key Bone Formation Facts
| 72. | What three processes involve intramembranous bone formation? | 72. | Flat bone Distraction osteogenesis (except if unstable) Blastema (after amputation) |
| 73. | What two processes involve appositional bone formation? | 73. | Periosteal enlargement Bone formation with remodeling |
| 74. | What process of bony healing is seen with rigid plating? | 74. | Haversian remodeling |
Enchondral Ossification
| 75. | At what relative oxygen tension does enchondral calcification occur? | 75. | Low oxygen tension |
| 76. | Growth plate chondrocytes produce what protein? | 76. | Indian hedgehog protein |
| 77. | What is the function of this protein? | 77. | Signals release of parathyroid hormone-related peptide (PTHrP) production |
| 78. | What is the ultimate effect? | 78 | Inhibits chondrocyte maturation |
| 79. | What disorder results from mutation in PTHrP? | 79. | Jansen’s metaphyseal dysplasia |
| 80. | The perichondral ring of Lacroix is continuous with what structure? | 80. | Groove of Ranvier |
| 81. | What are the two functions of the ring? | 81. | Provides mechanical support to bone-cartilage junction Contributes chondrocytes to increase bone latitudinal growth |
classification of Enchondral ossification Disorders by Location
List the key disorders for each location:
| 82. | Epiphyseal dysplasias (three)? | 82. | Spondyloepiphyseal dysplasia Chondrodysplasia punctata Multiple epiphyseal dysplasia |
| 83. | Reserve zone (four)? | 83. | Pseudachondroplasia Kniest Diastrophic dysplasia Gaucher’s/Niemann-Pick |
| 84. | Proliferative zone (three)? | 84. | Achondroplasia Gigantism Hypochondroplasia |
| 85. | Hypertrophic zone? | 85. | Mucopolysaccharidoses (e.g., Morquio’s, Hurler’s) |
| 86. | Zone of provisional calcification (four)? Exception? | 86. | Rickets/osteomalacia SCFE (exception: renal failure SCFE occurs at spongiosa) Physeal fracture Enchondroma |
| 87. | Primary spongiosa (two)? | 87. | Metaphyseal chondrodysplasia (e.g., Jansen, Schmid) Osteomyelitis |
| 88. | Secondary spongiosa (three)? | 88. | Osteopetrosis Osteogenesis imperfecta Scurvy |
Spondyloepiphyseal Dysplasias
| 89. | What is (are) the two associated inheritance patterns? | 89. | Congenita: AD Tarda: X-linked |
| 90. | What is the mutation? | 90. | Type II collagen |
| 91. | What is the gene? | 91. | COL2A1 |
| 92. | What is the zone? | 92. | Epiphyseal |
| 93. | Does the disorder result in proportionate or disproportionate dwarfism? | 93. | Disproportionate |
| 94. | What is the subclassification (short limb or short trunk)? | 94. | Short trunk |
| 95. | Spondyloepiphyseal dysplasia must be differentiated from which disorder? | 95. | Multiple epiphyseal dysplasia (MED) |
Spondyloepiphyseal Dysplasia Congenita
| 96. | What is the relative severity of congenita? | 96. | More severe than tarda |
| 97. | What is the key feature of the face? | 97. | Flat |
| 98. | What are the two key features of the hips? | 98. | Delayed epiphyseal appearance Coxa vara |
| 99. | What are the two key features of the spine? | 99. | Odontoid hypoplasia Vertebral beaking |
| 100. | What is the key feature of the knees? | 100. | Genu valgum |
| 101. | What is the key feature of the feet? | 101. | Clubfeet |
Spondyloepiphyseal Dysplasia Tarda
| 102. | Relative severity? | 102. | Less severe |
| 103. | What is the key feature of the legs? | 103. | No angular deformity |
| 104. | In all types of spondyloepiphyseal dysplasia, what organ must be checked? For what? | 104. | Eyes, for retinal detachment |
Chondrodysplasia Punctata
| 105. | What are the two inheritance forms? | 105. | AD, as in Conradi-Hunermann Autosomal recessive (AR) |
| 106. | What is the mutation? | 106. | Peroxisomal enzymatic defect |
| 107. | What is the relative severity of Conradi-Hunermann? What are the key features? | 107. | Less severe Variable features |
| 108. | What is the relative severity of the AR form? Rhizo, meso, or acro? What is the prognosis? | 108. | More severe Rhizomelic dwarfism Fatal early |
| 109. | What is the x-ray appearance of either type? | 109. | Multiple punctate calcifications |
Multiple Epiphyseal Dysplasia
| 110. | What is the inheritance? | 110. | AD |
| 111. | What are the two mutations? | 111. | Collagen IX COMP (cartilage oligometric matrix protein) |
| 112. | What is the zone? | 112. | Epiphysis |
| 113. | Proportionate or disproportionate? | 113. | Disproportionate |
| 114. | What is the subclassification (short limb or short trunk)? | 114. | Short limb |
| 115. | What is the defining feature? | 115. | Irregular delayed ossification at multiple epiphyses |
| 116. | What is the key feature of the hips? Rule out? | 116. | Coxa vara Rule out Perthes |
| 117. | What are the three key features of the knees? | 117. | Flat femoral condyles Double-layer patella Genu valgum |
| 118. | What three MED features are not seen in Perthes? | 118. | Bilateral symmetric involvement Early acetabular changes No metaphyseal cysts |
| 119. | If you see bilateral Legg-Calvé-Perthes disease (LCPD) and want to check for dysplasia, what is the test of choice? | 119. | Skeletal survey |
Disorders of the Reserve Zone
Pseudoachondroplasia
| 120. | What is the inheritance? | 120. | AD |
| 121. | What is the mutation? | 121. | COMP |
| 122. | What is the zone? | 122. | Reserve |
| 123. | What is the key feature of the face? | 123. | Normal |
| 124. | What is the key feature of the spine? | 124. | Cervical instability |
| 125. | What are the two key features of the joints? | 125. | Flexion contractures Osteoarthritis |
| 126. | What are the two general characteristics of the x-ray appearance? | 126. | Metaphyseal flaring Delayed epiphyseal ossification |
Kniest Dysplasia
| 127. | What is the inheritance? | 127. | AD |
| 128. | What is the mutation? | 128. | Type II collagen |
| 129. | What is the zone? | 129. | Reserve zone |
| 130. | Proportionate or disproportionate? | 130. | Disproportionate |
| 131. | What is the subclassification? | 131. | Short trunk |
| 132. | What is the key feature of the joints? | 132. | Contractures |
| 133. | What is the femoral appearance? | 133. | Dumbbell shaped |
| 134. | What two clinical problems is it associated with? | 134. | Retinal detachment Cleft palate |
Diastrophic Dysplasia
| 135. | What is the inheritance? | 135. | AR |
| 136. | What is the mutation? | 136. | Sulfate transport protein on chromosome 5 |
| 137. | What is the zone? | 137. | Reserve |
| 138. | Proportionate or disproportionate? | 138. | Disproportionate |
| 139. | What is the subclassification? | 139. | Short limb |
| 140. | What are the two key features of the face? | 140. | Cleft palate Cauliflower ears |
| 141. | What are the two key features of the spine? What is the natural history? | 141. | Atlantoaxial instability Cervical kyphosis: spontaneously resolves |
| 142. | What is the key feature of the joints? | 142. | Contractures |
| 143. | What is the key feature of the hips? | 143. | Dysplasia |
| 144. | What are the two key features of the feet? | 144. | Bilateral skewfoot Rigid clubfoot |
| 145. | What is the key feature of the hands? | 145. | Hitchhiker thumbs |
Gaucher
| 146. | What is the inheritance? | 146. | AR |
| 147. | What is the zone? | 147. | Reserve |
| 148. | What is the classification? | 148. | Lysosomal storage disease |
| 149. | What is accumulated? | 149. | Cerebroside |
| 150. | What population is particularly at risk? | 150. | Ashkenazi Jews |
| 151. | What is the key feature of the hips? | 151. | Femoral head necrosis |
| 152. | What is the key feature of the knees? | 152. | Erlenmeyer flask shaped distal femur |
| 153. | What is the key feature of the organs? | 153. | Hepatosplenomegaly (HSM) |
| 154. | What is the key feature of the pain? | 154. | Bone pain indicates Gaucher crisis |
| 155. | What is the x-ray appearance of involved bone? | 155. | Moth-eaten |
Niemann-Pick
| 156. | What is the inheritance? | 156. | AR |
| 157. | What is accumulated? | 157. | Sphingomyelin |
| 158. | What are the two key features of the bones? | 158. | Expanded marrow space Cortical thinning |
Disorder of the Proliferative Zone: Achondroplasia
| 159. | What is the inheritance? | 159. | AD |
| 160. | What is the mutation? | 160. | FGFR3 on chromosome 4 Defect causes FGFr3 to be constituently active |
| 161. | What is the zone? | 161. | Proliferative |
| 162. | Proportionate or disproportionate? | 162. | Disproportionate |
| 163. | What is the subclassification? | 163. | Short limb |
| 164. | What is the parental risk factor? | 164. | Advanced paternal age |
| 165. | Rhizo, meso, or acro? | 165. | Rhizomelic (proximal involvement) |
| 166. | What is the key feature in general? | 166. | Ligamentous laxity |
| 167. | What are the two key features of the face? | 167. | Frontal bossing Midface hypoplasia |
| 168. | What is the key feature of the hands? | 168. | Trident |
| 169. | What are the three key features of the spine? | 169. | Lumbar stenosis (short pedicles) Foramen magnum stenosis Kyphosis |
| 170. | What is the prognosis for an infant with kyphosis? What is the treatment? | 170. | Usually spontaneously resolves Extension brace until over 2 years old |
| 171. | What is the x-ray feature of the spine? | 171. | Decreased interpedicular distance |
| 172. | What is the key feature of the pelvis? | 172. | Champagne glass |
| 173. | What are the two key features of the knees? | 173. | Genu varum Inverted V distal femoral physis |
| 174. | What are two components of thanatophoric dysplasia? | 174. | Achondroplasia Restrictive lung disease |
Disorders of the Hypertrophic Zone: Mucopolysaccharidoses
| 175. | What is the zone? | 175. | Hypertrophic zone |
| 176. | Proportionate or disproportionate? | 176. | Proportionate |
| 177. | What is the most common type? | 177. | Morquio’s |
| 178. | What type results in the shortest height? | 178. | Morquio’s |
| 179. | What type has the worst prognosis? | 179. | Hurler’s, fatal by age 10 |
| 180. | What is the general feature of the hips? | 180. | Coxa vara |
| 181. | What are the two general features of the spine? | 181. | Vertebral beaking Odontoid hypoplasia/instability: may lead to myelopathy |
| 182. | What is the general feature of the hands? | 182. | Bullet metacarpals |
| 183. | What is the general feature of the knees? | 183. | Genu valgum |
Hunter
| 184. | What is the inheritance? | 184. | X linked recessive |
| 185. | Intelligence is generally ________? | 185. | Decreased |
| 186. | What is the key feature of the cornea appearance? | 186. | Clear |
| 187. | What is excreted in urine? | 187. | Dermatan/heparan sulfate |
Hurler
| 188. | What is the inheritance? | 188. | AR |
| 189. | What is the mutation? | 189. | Alpha-L-iduronidase |
| 190. | Intelligence is generally ________? | 190. | Decreased |
| 191. | What is the key feature of the cornea appearance? | 191. | Cloudy |
| 192. | What is excreted in urine? | 192. | Dermatan/heparan sulfate |
Morquio
| 193. | What is the inheritance? | 193. | AR |
| 194. | What is the mutation? | 194. | N-acetylgalactose-6 sulfate |
| 195. | Intelligence is generally ________? | 195. | Normal |
| 196. | What is the key feature of the cornea appearance? | 196. | Cloudy |
| 197. | What is excreted in urine? | 197. | Keratan sulfate |
Sanfilippo
| 198. | What is the inheritance? | 198. | AR |
| 193 | |||
| 199. | Intelligence is generally ________? | 199. | Decreased |
| 200. | What is the key feature of the cornea appearance? | 200. | Clear |
| 201. | What is excreted in urine? | 201. | Heparan sulfate |
| 202. | What feature is unique to Sanfilippo? | 202. | Development is normal until age 2 |
Disorders Specific to the Zone of Provisional Calcification
Rickets/Osteomalacia
| 203. | What is the zone? | 203. | Zone of provisional calcification |
| 204. | What are the two qualities of affected bone? | 204. | Brittle Bowed long bones |
| 205. | What is the key feature of the physis? | 205. | Cupped and widened |
| 206. | What is the key feature of the skull? | 206. | Flat |
| 207. | What is the key feature of the knees? | 207. | Genu varum |
| 208. | What is the key feature of the ribs? | 208. | Rachitic rosary at costochondral junction |
| 209. | What is the key feature of the spine? | 209. | Dorsal kyphosis |
| 210. | What are the two histologic features of rickets? | 210. | Wide osteoid seams Swiss cheese trabeculae |
| 211. | What is a milkman’s fracture? | 211. | Pseudofracture on compression side of bone |
Disorders of the Primary Spongiosa: Metaphyseal Chondrodysplasias
| 212. | What is the zone? | 212. | Primary spongiosa |
| 213. | What is the condition of the epiphysis? | 213. | Normal |
| 214. | Proportionate or disproportionate? | 214. | Disproportionate |
| 215. | What is the subclass? | 215. | Short limb |
| 216. | What are the three types of metaphyseal chondrodysplasia? | 216. | Jansen Schmid McKusick |
Jansen
| 217. | What is the inheritance? | 217. | AD |
| 218. | What is the mutation? | 218. | PTHrP |
| 219. | What is the relative severity? | 219. | Most severe |
| 220. | What are the two key features? | 220. | Hypercalcemia Bulbous metaphyseal expansion |
Schmid
| 221. | What is the inheritance? | 221. | AD |
| 222. | What is the mutation? | 222. | Type X collagen |
| 223. | What is the relative severity? | 223. | Less severe |
| 224. | What disorder must be excluded? | 224. | Rickets |
| 225. | What is the key feature of the hips? | 225. | Coxa vara |
| 226. | What is the key feature of the knees? | 226. | Genu varum |
McKusick
| 227. | What is the inheritance? | 227. | AR |
| 228. | What population is particularly at risk? | 228. | Amish |
| 229. | What is McKusick also known as? | 229. | Cartilage-hair dysplasia |
| 230. | What are the two key features? | 230. | Odontoid hypoplasia and cervical instability Fibular overgrowth |
Disorders of the Secondary Spongiosa
Osteopetrosis
| 231. | What are the two forms of the inheritance? | 231. | AD (mild form) AR (malignant form) |
| 232. | The autosomal dominant form is also known as what? | 232. | Albers-Schönberg disease |
| 233. | What is the mutation? | 233. | Carbonic anhydrase defect Chromosome 11 |
| 234. | What is the zone? | 234. | Secondary spongiosa |
| 235. | Where does the defect manifest itself? | 235. | Thymus |
| 236. | This results in failure of what? | 236. | Osteoclastic resorption |
| 237. | What is the histologic characteristic? | 237. | Osteoclasts without ruffled border |
| 238. | What are the key molecules involved in osteoclast development and bone remodeling? | 238. | RANKL: expressed on osteoblasts RANK: expressed on osteoclasts OPG (osteoprotegrin): produced by osteoblasts RANKL binds to RANK on osteoclast precursors leading to osteoclast differentiation, hence increased bone resorption OPG acts as decoy receptor for RANKL inhibiting osteoclastogenesis Nude mice knockout model: knock out RANKL → osteopetrosis |
| 239. | What is the quality of affected bone? | 239. | Dense (marble) |
| 240. | What is the key feature of the spine? | 240. | Rugger jersey: looks like stripes on a lateral film |
| 241. | What is the key feature of the knee? | 241. | Erlenmeyer flask shaped distal femur |
| 242. | What is the three treatments for the malignant form of disease? | 242. | Bone marrow transplant Calcitriol with or without steroids Interferon-gamma-1β |
Osteogenesis Imperfecta
| 243. | What is the mutation? | 243. | Type I collagen |
| 244. | What is the gene? | 244. | COL1A2 |
| 245. | What is the zone? | 245. | Secondary spongiosa |
| 246. | By what two means is osteogenesis imperfecta diagnosed? | 246. | Skull films Fibroblast culture |
| 247. | What is the quality of affected bone? | 247. | Brittle |
| 248. | What is characteristic about the height? | 248. | Short |
| 249. | What is the key feature of the ligaments? | 249. | Lax |
| 250. | What is characteristic about the fracture healing? | 250. | Normal But remodeling is increased |
| 251. | What intervention should be considered when the patient is over 2 years old? | 251. | Consider prophylactic intramedullary (IM) nails |
| 252. | What are two possible early interventions? | 252. | Bracing Sofield osteotomy for bow or fracture |
| 253. | What is the key feature of the spine? When should surgery be considered? | 253. | Scoliosis Operate when curve over 50 degrees |
| 254. | What is the key feature of the brainstem? | 254. | Basilar invagination |
| 255. | What is the best pharmacologic therapy? | 255. | Bisphosphonate therapy |
| 256. | What are the three benefits of bisphosphonate therapy? | 256. | Improved cortical thickness Decreased incidence of fracture Improved height of collapsed vertebral bodies |
| 257. | Do bisphosphonates help the scoliosis? | 257. | No |
| 258. | Classify the four types by relative severity (from most severe to least)? | 258. | II III I IV |
Type I
| 259. | What is the inheritance? | 259. | AD |
| 260. | What is the sclera appearance? | 260. | Blue |
| 261. | When do children generally present with disease? | 261. | Preschool age |
| 262. | How is hearing characteristically affected? | 262. | Hearing loss |
Type II
| 263. | What is the inheritance? | 263. | AR |
| 264. | What is the sclera appearance? | 264. | Blue |
| 265. | What is the prognosis? | 265. | Lethal early |
Type III
| 266. | What is the inheritance? | 266. | AR |
| 267. | What is the sclera appearance? | 267. | White |
| 268. | How do children with type III generally present? | 268. | Fractures at birth |
Type IV
| 269. | What is the inheritance? | 269. | AD |
| 270. | What is the sclera appearance? | 270. | White |
| 271. | What is the relative severity of type IV in relation to other types? | 271. | Mild |
| 272. | What is the key feature of the hearing? | 272. | Normal |
Scurvy
| 273. | What is the zone? | 273. | Secondary spongiosa |
| 274. | Scurvy results from a deficiency of what? | 274. | Vitamin C |
| 275. | Vitamin C deficiency then leads to a deficiency of what? | 275. | Chondroitin sulfate |
| 276. | What is the ultimate effect? | 276. | Impaired collagen growth and hydroxylation |
| 277. | What is the key systemic feature? | 277. | Fatigue |
| 278. | What is the key feature of the gums? | 278. | Bleeding gums |
| 279. | What is the key feature of the joints? | 279. | Effusions |
| 280. | What are the two key x-ray findings? | 280. | Thin cortices Metaphyseal clefts |
| 281. | Why do the clefts develop? | 281. | From compression fractures |
| 282. | What can be seen around the ossification centers? | 282. | Lines |
Disorders of Intramembranous Ossification
Cleidocranial Dysostosis
| 283. | What is the inheritance? | 283. | AD |
| 284. | What is the mutation? | 284. | CBFA1 on chromosome 6 |
| 285. | What are the two functions of mutant protein? | 285. | Osteoblast differentiation Osteocalcin expression |
| 286. | What is the zone? | 286. | No zone |
| 287. | Why? | 287. | Because intramembranous, not enchondral, ossification affected |
| 288. | Proportionate or disproportionate? | 288. | Proportionate |
| 289. | Is it usually unilateral or bilateral? | 289. | Usually unilateral |
| 290. | Is the whole clavicle missing? | 290. | Usually lateral clavicle absent only But sometimes the whole clavicle is absent (appearance of touching shoulders) |
| 291. | What is the key feature of the head? | 291. | Delayed skull suture closure |
| 292. | What is the key feature of the hips? | 292. | Coxa vara |
| 293. | What is the key feature of the pelvis? | 293. | Widened symphysis pubis |
Congenital Pseudarthrosis of the Clavicle
| 294. | What clavicle is most commonly affected with congenital pseudarthrosis? | 294. | Right |
| 295. | Is involvement generally unilateral or bilateral? | 295. | Unilateral |
| 296. | What portion of the clavicle is missing? | 296. | Center: medial and lateral clavicle not united |
| 297. | How are the majority of patients with congenital pseudarthrosis successfully treated? | 297. | Nonoperatively |
| 298. | What is the indication for surgery with this condition? | 298. | Scapular winging |
Review of Key Disorders and Features: Quick Solution Guide
Name the disorders associated with each of the listed features:
| 299. | Short trunk dwarfism (two)? | 299. | Kniest Spondyloepiphyseal dysplasia |
| 300. | Proportional dwarfism (two)? | 300. | Mucopolysaccharidoses Cleidocranial dysostosis |
| 301. | Odontoid hypoplasia/cervical instability (seven)? | 301. | Pseudachondroplasia SED (spondyloepiphyseal dysplasia) congenita McKusick (metaphyseal chondrodysplasia) Morquio (mucopolysaccharidosis) Diastrophic dysplasia Down syndrome Neurofibromatosis |
| 302. | Joint contractures (four)? | 302. | Kniest Diastrophic dysplasia Arthrogryposis Pseudachondroplasia |
| 303. | Joint dislocations (two)? | 303. | Ehlers-Danlos Larsen’s syndrome |
| 304. | Other disorders with laxity (three)? | 304. | Osteogenesis imperfecta Fragile X Down syndrome |
| 305. | Genu valgum (four)? | 305. | SED congenita MED Ellis-van Creveld Multiple hereditary exostoses (MHE) |
| 306. | Genu varum (four)? | 306. | Achondroplasia Schmid (metaphyseal chondrodysplasia) Rickets Osteogenesis imperfecta (OI) |
| 307. | Coxa vara (five)? | 307. | SED congenita MED Schmid (metaphyseal chondrodysplasia) Morquio (mucopolysaccharidosis) Cleidocranial dysostosis |
| 308. | Erlenmeyer flask-shaped distal femur (two)? | 308. | Gaucher’s Osteopetrosis |
| 309. | Rugger jersey spine (two)? | 309. | Osteopetrosis Renal osteodystrophy |
| 310. | Obese, decreased IQ (two)? | 310. | Prader-Willi Albright’s (pseudo-hypoparathyroidism) |
| 311. | Biconcave vertebrae (two)? | 311. | Osteoporosis/osteomalacia (due to compression fracture) Sickle cell disease |
| 312. | Thymic defect or antibodies versus thymus (two)? | 312. | Myasthenia gravis (competitive inhibitor) Osteopetrosis |
Other Commonly Tested Pediatric Syndromes
List of Syndromes and Features
Laron’s Dysplasia
| 313. | What is the inheritance? | 313. | AR |
| 314. | What is the mutation? | 314. | Deficient growth hormone (GH) receptor |
| 315. | Laron’s dysplasia is also known as what? | 315. | Pituitary dwarfism |
Progressive Diaphyseal Dysplasia (Camurati-Engelmann)
| 316. | What is the inheritance? | 316. | AD |
| 317. | What is the defining feature? | 317. | Symmetric cortical thickening of long bones |
| 318. | What is the usual treatment of this disorder? | 318. | Nonsteroidal antiinflammatory drugs (NSAIDs) |
Dysplasia Epiphysealis Hemimelia (Trevor’s)
| 319. | What is the defining feature of Trevor’s? | 319. | Epiphyseal osteochondroma (knee) |
Fascioscapulohumeral Dystrophy
| 320. | What is the inheritance? | 320. | AD |
| 321. | What is the creatine phosphokinase (CPK) level in these patients? | 321. | Normal |
| 322. | What are the two key features? | 322. | Facial weakness Proximal shoulder weakness bilaterally with winging |
| 323. | What is the treatment if weakness is severe? | 323. | Scapulothoracic fusion |
Limb-Girdle Dystrophy
| 324. | What is the inheritance? | 324. | AR |
| 325. | What is the genetic defect? | 325. | Sarcoglycan defect |
| 326. | What is the CPK level? | 326. | Elevated |
| 327. | What two areas are affected? | 327. | Shoulder Pelvis |
Ellis-van Creveld
| 328. | What is the inheritance? | 328. | AR |
| 329. | What is the gene? | 329. | EVC gene |
| 330. | What are the two key features of the digits? | 330. | Polydactyly Nail abnormalities |
| 331. | What are the two key features of the knees? | 331. | Genu valgum Abnormal patellofemoral joints |
| 332. | What is the key feature of the heart? | 332. | Congenital heart disease |
Nail-Patella Syndrome
| 333. | What is the inheritance? | 333. | AD |
| 334. | What is the gene? | 334. | Lim homeobox (LMX1B): regulates transcription in limb-patterning and kidney formation |
| 335. | What are the two features of the knee? | 335. | Genu valgum Absent patellae |
| 336. | When does the patella normally ossify? | 336. | At age 3 to 6 years |
| 337. | At which other joint is increased valgus also seen? | 337. | Elbows |
| 338. | What two other conditions must be excluded with nail-patella syndrome? | 338. | Kidney disease Glaucoma |
| 339. | What radiographic feature is common to both Ellis-van Creveld and nail-patella syndromes? | 339. | Iliac horns |
McCune-Albright Syndrome
| 340. | What is the inheritance? | 340. | None; sporadic mutation |
| 341. | What is the mutation? Activating or deactivating? | 341. | Gs-α adenylate cyclase coupling Activating |
| 342. | What is the key feature of the bone? | 342. | Fibrous dysplasia |
| 343. | What is the key feature of the skin? | 343. | Café-au-lait spots |
| 344. | What is the timing of puberty? | 344. | Precocious |
Dyschondrosteosis (Lerri-Weill Syndrome)
| 345. | What is the inheritance? | 345. | AD |
| 346. | What is the gene? | 346. | SHOX gene |
| 347. | What is the key feature of the height? | 347. | Short |
| 348. | Dyschondrosteosis is associated with what peripheral deformity? | 348. | Madelung’s deformity |
Fragile X
| 349. | What sex is affected? | 349. | Male |
| 350. | What is the key feature of the joints? | 350. | Lax |
| 351. | What is the key feature of the feet? | 351. | Flat |
| 352. | What is the key feature of the spine? | 352. | Scoliosis |
| 353. | What is the key feature of the gonads? | 353. | Macro-orchidism |
Down Syndrome
| 354. | What is the mutation? | 354. | Trisomy 21 |
| 355. | What are the two key features of the hips? | 355. | Slipped capital femoral epiphysis (SCFE) (hypothyroidism) Instability |
| 356. | What is the key feature of the feet? | 356. | Pes planus |
| 357. | What is the key feature of the spine? | 357. | Atlantoaxial instability |
| 358. | What is the key feature of the ligaments? | 358. | Lax |
| 359. | What are the two key endocrine features? | 359. | Hypothyroidism Diabetes mellitus |
| 360. | What is the key cardiovascular feature? | 360. | Heart disease |
| 361. | What is the treatment for an asymptomatic Down syndrome child with atlantoaxial instability? | 361. | No contact sports Fusion if ADI >10 mm (ADI = atlanto-dens interval) |
| 362. | Quick review: With what four cervical spine conditions are contact sports contraindicated? | 362. | Congenital upper cervical fusions or instability (e.g., os odontoideum) Grade II spondylolisthesis Atlantoaxial instability (e.g., Down syndrome) History of diffuse axonal injury |
Turner’s Syndrome
| 363. | What is the mutation? | 363. | 45XO |
| 364. | What sex is affected? | 364. | Females |
| 365. | What is the key feature of the height? | 365. | Short |
| 366. | What is the key feature of the neck? | 366. | Webbed |
| 367. | What is the key feature of the elbows? | 367. | Cubita valga |
| 368. | Turner’s syndrome is associated with what anesthetic complication? | 368. | Malignant hyperthermia |
| 369. | Turner’s must be differentiated from what similar syndrome? | 369. | Noonan’s syndrome |
| 370. | In what three ways is Noonan’s different? | 370. | Normal gonads Mental retardation Severe scoliosis |
| 371. | Quick review: What three disorders are also associated with malignant hyperthermia? | 371. | Duchenne’s muscular dystrophy (MD) Arthrogryposis Osteogenesis imperfecta |
| 372. | How is an individual at risk for malignant hyperthermia diagnosed? | 372. | Muscle biopsy |
| 373. | What is the pharmacologic treatment for malignant hyperthermia? | 373. | Dantrolene |
Prader-Willi
| 374. | Prader-Willi is associated with what genetic concept? | 374. | Imprinting (parent with mutation determines the disorder) |
| 375. | What is the mutation? | 375. | Partial chromosome 15 deletion (paternal) |
| 376. | The same mutation inherited from the mother results in what syndrome? | 376. | Angelman’s syndrome |
| 377. | What is the key Prader-Willi feature in the infant? | 377. | Hypotonic |
| 378. | What are the three key Prader-Willi features in the adult? | 378. | Obesity Mental retardation Hypogonadism |
Menkes’ Syndrome
| 379. | What is the inheritance? | 379. | X-linked recessive (XLR) |
| 380. | What is the mutation? | 380. | Copper transport protein |
| 381. | What is the key feature of the hair? | 381. | Kinky hair |
| 382. | What other disorder has similar features? | 382. | McKusick (metaphyseal chondrodysplasia) |
Rett’s Syndrome
| 383. | What sex is affected? | 383. | Female |
| 384. | When do symptoms generally present? | 384. | At age 6 to 18 months |
| 385. | Is Rett’s a static or progressive condition? | 385. | Progressive |
| 386. | What is the key feature of the movement disorder? | 386. | Stereotaxic hand movements |
| 387. | What is the key feature of the spine? | 387. | Scoliosis |
| 388. | Can Rett’s scoliosis be braced? | 388. | Unresponsive to bracing |
Beckwith-Wiedemann
| 389. | What is the key orthopaedic feature of this disease? | 389. | Hemihypertrophy |
| 390. | What is the triad of other classic features? | 390. | Organomegaly Omphalocele Large tongue |
| 391. | What two neoplasms are associated with Beckwith-Wiedemann? | 391. | Wilms’ nephroblastoma Hepatoblastoma |
| 392. | How are affected patients screened for neoplasm development? | 392. | Serial abdominal ultrasounds until age 5 Serial α-fetoprotein (AFP) level until age 3 |
| 393. | What condition is the next most common cause of hemihypertrophy? | 393. | Neurofibromatosis |
| 394. | In that case, what is hemihypertrophy due to? | 394. | Plexiform neurofibroma |
Marfan Syndrome
| 395. | What is the inheritance? | 395. | AD |
| 396. | What is the mutation? | 396. | Fibrillin |
| 397. | What is the chromosome? | 397. | 15 |
| 398. | What is the key feature of the eye? | 398. | Superior dislocation of the lens |
| 399. | What is the key feature of the chest? | 399. | Pectus deformity |
| 400. | What are the two key cardiovascular features? What is the preferred pharmacologic treatment? | 400. | Valvular abnormalities Aortic arch enlargement Beta-blockers to minimize aortic dissection |
| 401. | What is the key feature of the spine? What is the usual treatment? | 401. | Scoliosis Surgery usually necessary (bracing ineffective) |
| 402. | What is the key feature of the hips? | 402. | Protrusio |
Homocystinuria
| 403. | What is the inheritance? | 403. | AR |
| 404. | What is the enzyme defect? | 404. | Cystathionine synthetase |
| 405. | The defective enzyme then results in abnormal metabolism of what? |
