Developmental Bone Disorders

Question 1

Achondroplasia mechanism

Answer 1

Substitution mutation of an arginine for glycine in FGFR3 on chromosome 4

Question 2

Achondroplasia clinical features

Answer 2

Foramen magnum stenosis, thoracolumbar kyphosis, spinal stenosis, genu varum (bow legged knees), short stature, trident hand

Question 3

Osteopetrosis mechanism

Answer 3

Heritable disorder caused by a defect in osteoclastic resorption (defect in acidification of bone) leading to dense and brittle bone

Question 4

Osteopetrosis clinical features

Answer 4

Advanced osteoarthritis, rugged jersey spine

Question 5

Osteogenesis imperfecta mechanism

Answer 5

Generally autosomal dominant (sometimes autosomal recessive) mutation in COL1A leading to abnormal type I collagen formation, seen in areas where type I collagen is used, like bones, teeth, ligaments, and sclera

Question 6

Osteogenesis imperfecta classifications

Answer 6

Types I-IV, with type III being the worst one

Question 7

Osteogenesis imperfecta clinical features

Answer 7

Blue sclera, triangular faces, defective dentition, macrocephaly, scoliosis, limb deformities, joint laxity, hearing loss, growth retardation

Question 8

Osteogenesis imperfecta lab findings

Answer 8

Microscopic analysis of collagen (would not see triple helixes), or DNA analysis for COL1A (or other associated mutations)

Question 9

Osteogenesis imperfecta radiographic findings, skull

Answer 9

Wormian bones, enlargement of frontal and mastoid sinuses, platybasia (flattened base of the skull) with or without basilar impression

Question 10

Osteogenesis imperfecta radiographic findings, thoracic cage

Answer 10

Fractured and beaded ribs, pectus carinatum (outward bowing of chest)

Question 11

Osteogenesis imperfecta radiographic findings, pelvis and femurs

Answer 11

Narrow pelvis, protrusion acetabuli (head of femur trying to punch through hip socket), Shepard’s crook deformity of the femurs (coxa vera - bowed hip)

Question 12

Osteogenesis imperfecta radiographic findings, spine

Answer 12

Compression fractures, scoliosis

Question 13

Osteogenesis imperfecta radiographic findings, fractures

Answer 13

Typically transverse in the lower extremities, excessive callus formation and “popcorn” bones, multiple scalloped radiolucent areas with dense rims (from bisphosphate treatment), olecranon fractures

Question 14

Child abuse or bone disease?

Answer 14

Abuse: metaphyseal corner fractures, posteromedial rib fractures, eternal, scapular, and spinous process fractures
Bone disease: long bone fractures, clavicle fractures

Question 15

Osteogenesis imperfecta treatment

Answer 15

No cure, IV bisphosphate for a time, vitamin supplementation with calcium, phosphorus and vitamin D, surgical treatment with load sharing devices and intramedullary implants

Question 16

Marfan syndrome mechanism

Answer 16

Heritable disorder (autosomal dominant) caused by a genetic defect in FBN-1 that leads to abnormal collagen production and disorganized elastin

Question 17

Marfan syndrome clinical features

Answer 17

Tall stature, aortic root dilation, hypermobility, optic lens dislocation, striae

Question 18

Ehlers-Danlos syndrome mechanism

Answer 18

Heritable collagen and elastin defects

Question 19

Ehlers-Danlos syndrome clinical features

Answer 19

Fragile hyperelastic skin, joint hypermobility, early development of osteoarthritis and painful joint dislocations, striae

Question 20

Neurofibromatosis type 1 mechanism

Answer 20

Autosomal dominant mutation on chromosome 17

Question 21

Neurofibromatosis type 1 clinical features

Answer 21

Cafe-au-lait spots, neurofibromas, freckling (especially in axillae or inguinal region), optical glioma, lisch nodules, bone lesions, antero-lateral bowing of the tibia, scoliosis

Question 22

Neurofibromatosis type 2 mechanism

Answer 22

Autosomal dominant mutation in schwannomin gene

Question 23

Neurofibromatosis type 2 clinical features

Answer 23

Fewer peripheral neurofibromas, more intracranial lesions, especially acoustic neuromas (benign tumors on the nerve from inner ear to brain)