Orthopedic Developmental Pathology

Question 1

Syndrome with this Triad of findings- fibrous dysplasia of bone (polyostotic), cafe-au-lait skin pigmentation, endocrinopathies (hyperfunctioing)

Answer 1

McCune-Albright syndrome

Question 2

McCune Albright syndrome mutation

Answer 2

Mutation in regulatory gene (called GNAS) encoding protein of signal transduction (G-protein alpha subunit)
Mutation occurs well after fertilization (postzygotic mutation) since the disease is not vertically transmitted and lesions tend to respect midline of body
Mesenchymal stem cells (precursor pool of clasts, blasts, chondrocytes) are decreased

Question 3

disorder of craniofacial development- micrognathia (abnormally small jaw), microtia (small, malformed external ear/pinna), hypoplasia (underdevelopment) of midface, cleft palate often present, downward slanting palpebral fissures

Answer 3

Treacher Collins syndrome

Question 4

Treacher Collins gene mutation

Answer 4

Mutation of the gene (called TCOF1) encoding protein needed for proper control of ribosome activity
Autosomal dominant
Excessive apoptosis of neural crest cells
Mesenchymal stem cells and osteoblasts activity decreased

Question 5

Skeletal abnormalities of the upper limbs usually associated with congenital heart disease
Limb abnormalities may be bilateral or unilateral, short or absent forearm, absent digits, hypoplastic clavicles

Answer 5

Holt-Oram syndrome (AKA heart-hand syndrome)

Question 6

Holt-oram syndrome mutation

Answer 6

Mutation in the gene called TBX5 encoding a transcription factor called T-box 5 protein
Autosomal dominant
Early limb development involving mesenchyme progenitors of cartilage

Question 7

Short stature, upper arm and thigh commonly most shortened, midface hypoplasia (small nose), frontal bossing may be present (prominent forehead)

Answer 7

Achondroplastic dwarfism

Question 8

Achondroplasia defect in

Answer 8

Defective chondroblast development
Mutation in FGFR3 (fibroblast growth factor receptor 3)
Autosomal dominant or new mutations that were present in the gametes of older age fathers of normal height

Question 9

More severe than achondroplastic dwarfism, most common lethal form of dwarfism
Small, underdeveloped thoracic cavity leads to respiratory insufficiency

Answer 9

Thanatophoric dwarfism

Question 10

Thanatophoric dwarfism mutation

Answer 10

Mutation in FGFR3

Question 11

Deformity of the foot, 1/1000 births, affected foot is usually smaller than normal
Males affected more often
50% of cases are bilateral
No additional congenital anomalies elsewhere in the body

Answer 11

Clubfoot

Question 12

Complex structural abnormalities of clubfoot

Answer 12

Talus bone too small, malformed

Ultimately get varus configuration (turned inward)

Question 13

Clubfoot mutation

Answer 13

Multifactorial
Some have mutations in transcription factors- small subset of the homeodomain type (part of the protein that binds to specific regulatory regions of the target genes)
Decreased mesenchymal cells and osteoblasts activity

Question 14

Affects bones of children (weakened or softened)
Usually from prolonged vitamin D deficiency
Various skeletal changes may be present like bowing of the legs, frontal bossing of skull, chest protuberances (rachitic rosary)

Answer 14

Rickets

Question 15

Rickets abnormality

Answer 15

Abnormal osteochondral junction of rickets with disorder and poor mineralization

Question 16

Short stature with severe mental impairment
Occurs mainly in iodine deficient lands
Delayed and abnormal bone development
Thin, stunted limbs- poor periosteal ossification and poor enchondral ossification which leads to soft, weak epiphysial plates so you get separations or fragmentation
Skull malformations, poorly closed sutures

Answer 16

Cretinism

Question 17

Brittle bone disease
Mutation in gene encoding collagen chain
Prone to increased childhood fractures

Answer 17

Osteogenesis imperfecta

Question 18

Classical name of growth hormone deficiency
Short stature
Normal body proportions maintained

Answer 18

Pituitary dwarfism

Question 19

Skeletal changes- increased osteoclastic resorption, delayed matrix mineralization, short stature (stunted growth), osteoporosis
High turnover and low turnover subtypes
Phosphate retention pathology which induces secondary hyperparathyroidism and osteoclastic activity is stimulated as a result

Answer 19

Renal osteodystrophy

Question 20

Specific type of bone weakening in adults from vitamin D deficiency (related to rickets in children) prone to vertebral and femoral fractures

Answer 20

Osteomalacia

Question 21

Marble bone disease
Brittle bones due to osteoclastic dysfunction (impaired acidification)
Deposited bone not remodeled, much is woven bone (technically increased bone disease- but increase of immature bone)

Answer 21

Osteopetrosis

Question 22

Osteitis deformans that affects elderly adults
Chalkstick fracture
Gene mutation leads to increased osteoclastic activity followed by osteoblasts activity that finally burns out into a quiescent phase to get a region of abnormal bone with strange mosaic pattern under microscopy
Prone to fractures and sarcomas
Serum alkaline phosphatase levels may rise (produced by osteoblasts)

Answer 22

Paget disease

Question 23

Form of abnormal bone growth in adults with enlarged jaw, hands, feet
Caused by a type of pituitary adenoma
Secretes growth hormone
In children, this would cause gigantism (growth plates are still growing)

Answer 23

Acromegaly

Question 24

Growth plate fracture classification

Answer 24

Type 1- shear through plate, heals rapidly
Type 2- through growth plate and bone beneath it
Type 3- through growth plate and bone above it
Type 4- through growth plate and bone above and below it
Type 5- compression of plate, worst prognosis