Developmental Disorders of Bone and Cartilage

Question 1

Brachydactyly has a phenotype of

a. Short terminal phalanges of the first digits
b. Short stature
c. Sex reversal
d. Having an extra digit

Answer 1

Short terminal phalanges of the first digits

Question 2

What is the gene involved in brachydactyly?

Answer 2

HOXD13

Question 3

What is camptomelic dysplasia?
a. Short terminal phalanges of the first digits
B. Congenital anomalies abnormal clavicle
C. Sex reversal, abnormal skeleton development
D. Hypoplastic nails and patella

Answer 3

Sex reversal, abnormal skeleton development

Question 4

What is the gene involved in camptomelic dysplasia?

Answer 4

SOX9

Question 5

TBX5 gene mutation is associated with
A. Holt-Oram syndrome
B. Waardenburg syndrome 
C. Mail patella syndrome
D. Achondroplasia

Answer 5

Holt-Oram syndrome

Question 6

Holt-Oram syndrome has a phenotype of
A. Supernumerary teeth
B. Wormian bones
C. Congenital anomalies, forelimb anomalies
D. Hearing loss

Answer 6

Congenital anomalies, forelimb anomalies

Question 7

What is the phenotypes of the cleidocranial dysplasia?
A. Hearing loss, back pain and progressive nephropathy
B. Abnormal clavicles only
C. Abnormal clavicle, supernumerary teeth, wormian bones
D. Abnormal clavicle, hypoplatic nails and Wormian bones

Answer 7

Abnormal clavicle, supernumerary teeth, wormian bones

Question 8

What is the gene involved in cleidocranial dysplasia?

Answer 8

RUNX2

Question 9

What is the phenotype of Waardenburg syndrome type 1 and 3?
A. Hearing loss, abnormal pigmentation, craniofacial abnormalities
B. Hearing loss, abnormal clavicle, abnormal pigmentation
C. Hearing loss, brittle bones, craniofacial abnormalities
D. Supernumerary teeth, abnormal pigmentation, craniofacial abnormalities

Answer 9

Hearing loss, abnormal pigmentation, craniofacial abnormalities

Question 10

What is the gene involved in Waardenburg syndrome?

Answer 10

PAX3

Question 11

What is the gene involved in Nail-Patella syndrome?

Answer 11

LMX1B

Question 12

What is the phenotype of Nail-Patella syndrome?
A. Hypoplasia off nails, hypoplastic or aplastic patella, progressive nephropathy and dislocated radial heads
B. Hearing loss, brittle bones, craniofacial abnormalities
C. Hearing loss, back pain and progressive nephropathy
D. Hypoplasia off nails, hypoplastic or aplastic patella, progressive neuropathy and short stature

Answer 12

Hypoplasia off nails, hypoplastic or aplastic patella, progressive nephropathy and dislocated radial heads.

Question 13

Cleidocranial dysplasia is an autosomal ___________ (dominant/recessive) disorder

Answer 13

dominant

Question 14

_______ (gain/loss) of function mutation in RUNX2 results in cleidocranial dysplasia

Answer 14

Gain

Question 15

What is the phenotype of cleidocranial dysplasia?

Answer 15

Patent fontanelles
Delayed closure of cranial sutures
Delayed eruption of teeth
Supernumerary teeth
Abnormal clavicles
Short height
Wormian bone

Question 16

______________ (achondroplasia/osteogenesis imperfecta) is the most common form of dwarfism

Answer 16

Achondroplasia

Question 17

Achondroplasia is an _____________ (X-linked recessive/autosomal dominant) disorder resulting in retarded cartilage growth

Answer 17

autosomal dominant

Question 18

Achondroplasia has ___________ (rhizomelic/micromelic) shortening of limbs, frontal bossing, and depression of root of the nose.

Answer 18

rhizomelic

Question 19

In achondroplasia, 90% of cases stem from new mutations, almost all of which occur in the _________ (paternal/maternal) allele

Answer 19

paternal

Question 20

Achondroplasia is caused by gain-of-function mutations

in the _________________

Answer 20

FGF receptor 3 (FGFR3)

Question 21

Thanatophoric dysplasia is the most common _________ (lethal/non-lethal) form of dwarfism

Answer 21

lethal

Question 22

What are the features of thanatophoric dysplasia?

Answer 22

Micromelic limbs (disproportionately short or small limb)
Frontal bossing
Small chest
Bell-shaped abdomen

Question 23

How does death occurs in thanatophoric dysplasia?

Answer 23

A small chest cavity leads to respiratory insufficiency causing death

Question 24

Thanatophoric dysplasia is caused by mutations in _________

Answer 24

FGFR3

Question 25

One infantile form of osteopetrosis is associated with mutation of __________, resulting in decreased or absent osteoclasts

Answer 25

RANKL

Question 26

___________ is defined as reduced bone resorption and diffuse symmetric skeletal sclerosis due to impaired osteoclasts function/formation

Answer 26

Osteopetrosis

Question 27

What are the symptoms of osteopetrosis caused by mutations in LRP5?

Answer 27

High bone density Hearing loss Skeletal fragility

Question 28

What are the symptoms of osteopetrosis caused by mutations in RANKL?

Answer 28

High bone density

Question 29

What are the other names of osteopetrosis?

Answer 29

Marble bone disease | Albers-Schonberg disease

Question 30

Most of the mutations underlying osteopetrosis interfere with the process of acidification of the _______________

Answer 30

Osteoclastic resorption pit

Question 31

Autosomal recessive defects in the gene for the enzyme _______________is one main cause of osteopetrosis

Answer 31

Carbonic anhydrase 2

Question 32

CA2 is required by osteoclasts and renal tubular cells to generate __________ from carbon dioxide and water

Answer 32

Protons

Question 33

The absence of CA2 prevents osteoclasts from bone resorption, and also blocks the ___________ of urine by the renal tubular cells in osteopetrosis.

Answer 33

Acidification

Question 34

Osteopetrosis is caused by mutations in ________, which encodes a proton pump located on the surface of osteoclasts.

Answer 34

CLCN7

Question 35

Due to deficient osteoclast activity, bones involved by osteopetrosis ______ (lack/have) a medullary canal

Answer 35

Lack

Question 36

What is Erlenmeyer flask deformity?

Answer 36

The ends of long bones become bulbous and misshapen.

Question 37

Erlenmeyer flask deformity is found in ______________ (osteoporosis/osteopetrosis/osteomalacia/osteopenia)

Answer 37

Osteopetrosis

Question 38

What seems to be true about osteopetrosis? A. Mature trabeculae and small neural foramina B. Presence of primary spongiosa and no hematopoietic tissue

Answer 38

Presence of primary spongiosa and no hematopoietic tissue

Question 39

Deposited bone tends to be ________ (lamellar/woven) in architecture in the case of osteopetrosis.

Answer 39

Woven

Question 40

Severe infantile osteopetrosis is __________ (autosomal recessive/X-linked recessive)

Answer 40

Autosomal recessive

Question 41

Infantile osteopetrosis usually becomes evident in _______ (utero/second year of life)

Answer 41

Utero

Question 42

What are the clinical features of infantile osteopetrosis?

Answer 42

``` Fracture Anemia Hydrocephaly Cranial nerve defects Leukopenia Compensatory hepatosplenomegaly ```

Question 43

The mild autosomal dominant of osteopetrosis is discovered on x-ray studies performed because of __________

Answer 43

Repeated fractures

Question 44

Patient with autosomal dominant osteopetrosis may have mild cranial nerve deficits and _________

Answer 44

Anemia

Question 45

The affected enzymes are mainly ___________ in mucopolysaccharidoses

Answer 45

Acid hydrolases

Question 46

Mesenchymal cells, especially _______, normally degrade extracellular matrix mucopolysaccharides

Answer 46

Chondrocytes

Question 47

What is the pathophysiology of mucopolysaccharidoses?

Answer 47

1. Mucopolysaccharides accumulate inside the chondrocytes causing apoptotic death of the cells 2. They also accumulate in the extracellular space, resulting in structural defects in articular cartilage

Question 48

What are the clinical manifestations of mucopolysaccharidoses?

Answer 48

Short stature Chest wall abnormalities Malformed bones

Question 49

What is cartilage anlage?

Answer 49

Rudimentary form of the cartilage

Question 50

Where is cartilage anlage found in mucopolysaccharidoses?

Answer 50

Growth plates Costal cartilage Articulate surfaces

Question 51

Osteogenesis imperfecta is due to deficiency of type ___ collagen

Answer 51

Type I collagen

Question 52

OI principally affects bone, but also impacts other tissues rich in type I collagen. Give some examples of other tissues?

Answer 52

``` Joints eyes 👀 ears 👂 skin teeth 🦷 ```

Question 53

OI is usually due to ______________(Autosomal dominant/X-linked recessive)

Answer 53

Autosomal dominant

Question 54

In OI, there are mutations in the genes that encode the ____ and ____ chains of type I collagen

Answer 54

α1 | α2

Question 55

Many mutations in OI lead to replacement of a _______ residue with another amino acid in the triple-helical domain.

Answer 55

Glycine

Question 56

The fundamental abnormality in OI is too ________ (little/much) bone, resulting in extreme skeletal fragility.

Answer 56

Little bone

Question 57

What are the symptoms of OI?

Answer 57

Blue sclera Dental imperfections Hearing loss

Question 58

Type ____ OI is the lethal form off the disease

Answer 58

II

Question 59

The frequency of fractures ________ (decreases/increases) following puberty in type I osteogenesis imperfecta

Answer 59

Decreases

Question 60

``` What gene is mutated in osteopetrosis type 2? A. CA2 B. COL2A1 C. TBX5 D. CLCN7 ```

Answer 60

CLCN7

Question 61

Osteopetrosis type 2 is of _______ (early/late) onset

Answer 61

Late onset

Question 62

``` What gene is mutated in achondrogenesis type 2 A. COL10A1 B. COL2A1 C. RUNX2 D. CA2 ```

Answer 62

COL2A1

Question 63

What is the clinical phenotype of achondrogenesis type 2

Answer 63

Short trunk

Question 64

What gene is defected in metaphyseal dysplasia, Schmid type?

Answer 64

COL10A1