Congenital disorders of bone/cartilage

Question 1

function of Fibroblast growth factor receptor 3 (FGFR3)

Answer 1

Negative regulator of linear (endochondral) bone growth- inhibits growth + proliferation of chondrocytes

Question 2

Presentation of type 1 osteogenesis imperfecta

Answer 2

“BITE”

B: Bones (multiple fractures- mimic childabuse but bruising absent)

I: Eyes- blue sclera (thinning of type 1 collagen revealing underlying choroidal veins)

T: Teeth imperfection

E: Ear (hearing loss- ossicles easily fracture)

Question 3

Main difference between intramembranous ossification + endochondral ossification

Answer 3

In intramembranous ossification, bone is laid down directly by embryonic CT (mesenchyme) without pre-existing cartilage matrix- aggregated mesenchyme differentiate into osteoblasts.

In endochondral ossification, bone tissue replaces pre-existing hyaline cartilage, which is the template of future bones; this occurs at the growth plates.

Question 4

Characterized by abnormally thick, heavy bone due to defective osteoclast activity, resulting in overgrowth + sclersosis of shitty cortical bone

Answer 4

Osteopetrosis

Question 5

Presentation of thanatorphic dysplasia

Answer 5

Basically extreme form of achondroplasia

1) Extremely short limbs
2) Normal head
3) Associated w/ early death- due to chest collapse during delivery or inability of chest bones to support viscera

Question 6

Etiology of osteopetrosis

Answer 6

Poor osteoclast function/ numbers due to genetic defects in:

• CA II mutation: acidic environment required for resorption by osteoclasts
• RANKL/RANK

Question 7

Presentation of osteopetrosis

Answer 7

1) Bone fractures
2) Anemia, thrombocytopenia, leukopenia w/ extramedullary hematopoiesis- due to bony replacement of marrow
3) Vision + hearing impairment- impingement of crnial nerve as they exit skull
4) Hydrocephalus- narrowing of foramen magnum
5) Renal tubular acidosis- seen in CA II (decreased absorption of HCO3- in PCT)

Question 8

Etioloy of osteogenesis imperfecta

Answer 8

Variety of gene defects related to type 1 collagen (most commonly COL1A1 and COL1A2)

Question 9

Presentation of type 2 osteogenesis imperfecta

Answer 9

Perinatal letha

Question 10

Impaired cartilage proliferation in growth plate

Answer 10

Achondroplasia

Question 11

Imaging findings in osteopetrosis

Answer 11

Dense bone- “stone bone”

Erlenmeyer flask deformity

Question 12

Two types of osteogenesis imperfecta and two types of defects in molecules

Answer 12

Types of osteogenesis imperfecta:

• Type 1: mildest + most common form
• Type 2: Most severe form

Types of defects:

• Qualitative defects: Defective collagen type 1
• Quantitative dfects: less collagen type 1; however, quality normal (most common)

Question 13

Examples of bones formed by intramembranous ossification vs. endochondral ossofication

Answer 13

Intramembranous ossification- bones of head (skull, face, jaw)

Endochondral ossification- long bone development (appendicular skeleton, rib cage, axial skeleton)

Question 14

Presentation of achondroplasia and why?

Answer 14

1) Short extremities- defective endochondral ossification
2) normal chest/ trunk and head- normal intramembranous ossification
3) Spinal deformities common
4) Frontal bossing
5) Mental function, life span, fertlity unaffected

Question 15

Etiology of achondroplasia

Answer 15

AD ACTIVATING mutation in FGFR3

Most mutations are sporadic and related to increased paternal age

Question 16

Treatment of osteopetrosis

Answer 16

Bone marrow transplant (osteoclasts are derived from monocytes)

Question 17

Etiology of thanatorphic dysplais

Answer 17

Autosomal dominant/ denovo ACTIVATING mutation in FGFR3 gene