Hereditary Diseases Flashcards
(77 cards)
1
Q
Name five growth disorders of bone and cartilage
A
- Achondroplasia
- Cleidocranial dysplasia
- Marfan syndrome
- Osteogenesis imperfecta
- Osteopetrosis
2
Q
What is NORD?
A
National Organization for Rare Disorders
3
Q
What are some general considerations for hereditary bone and cartilage diseases?
A
- Autosomal dominant or recessive
- Spontaneous mutation
- Genetic/tissue component involved
- Life expectancy
- Clinical significance
4
Q
What is achondroplasia?
A
Congenital dwarfism (4’10” or less); the most common short limbed dwarfism
5
Q
Which chromosome is affected by achondroplasia?
A
Chromosome 4 (autosomal dominant mutation)
6
Q
How will a spontaneous mutation of chromosome 4 lead to achondroplasia?
A
- Defective fibroblast growth factor receptor 3 (FGFR3)
- Increased signaling suppresses proliferation and maturation of chondrocytes at growth plates
- Deficit in endochondral ossification
- Rhizomelic dwarfism (disproportionate length of proximal limb)
7
Q
What is the etiology of achondroplasia?
A
80% spontaneous mutations (but can be hereditary)
8
Q
What is the mentation and life span of someone with achondroplasia?
A
- Normal mentation
- Normal lifespan
9
Q
What is the average height of someone with achondroplasia?
A
Short stature averaging 50 inches (4’ 2”)
10
Q
If a patient presents with the following, what is the diagnosis?
- Normal length torso, shortened limbs
- Head to face ratio is altered with smaller foramen magnum
- Depressed nasal ridge
- Thoracic or thoracolumbar hyperkyphosis
- Lumbar hyperlordosis
A
Achondroplasia
11
Q
If a patient has the following radiographic features of the spine, what is the diagnosis?
- Posterior vertebral scalloping
- Bullet vertebrae
- Hyperlordosis with horizontal sacrum
- Congenital central stenosis
A
Achondroplasia
12
Q
What are the radiographic features of the spine in someone with achondroplasia?
A
- Posterior vertebral scalloping
- Bullet vertebrae
- Hyperlordosis with horizontal sacrum
- Congenital central stenosis
13
Q
If a patient has the following radiographic findings in the pelvis and extremities, what is the diagnosis?
- Short, broad metaphyses creating a waddling gait
- Champagne glass pelvis
- Flat ilia
- Horizontal sacrum
A
Achondroplasia
14
Q
What are the radiographic features of the pelvis and extremities in someone with achondroplasia?
A
- Short, broad metaphyses (creating waddling gate)
- Champagne glass pelvis
- Flat ilia
- Horizontal sacrum
15
Q
What are some treatments for achondroplasia?
A
- Orthopedic interventions
- Experimental treatment: FGFR3 gene modulation
16
Q
How does Rx growth hormone affect achondroplasia?
A
No effect
17
Q
Which chromosome is affected by cleidocranial dysplasia?
A
Chromosome 6 (autosomal dominant)
18
Q
How common is achondroplasia?
A
1/40,000 live births
19
Q
How common is cleidocranial dysplasia?
A
5 in 1 million births
RARE spontaneous mutation
20
Q
What deficit of ossification is involved in achondroplasia?
A
Endochondral
21
Q
Which type of ossification is deficient in cleidocranial dysplasia?
A
Intramembranous
22
Q
Which gene abnormality on chromosome 6 is causative of cleidocranial dysplasia?
What is it meant to do?
A
RUNX2 gene which helps encode osteoblasts
23
Q
What is the result of a spontaneous mutation of chromosome 6 affecting the RUNX2 gene?
A
Deficiency of intramembranous ossification
cleidocranial dysplasia
24
Q
Which bones are affected by cleidocranial dysplasia?
A
Flat bones: skull, clavicles
25
If a patient presents with the following, what is the diagnosis?
* Skull and clavicular anomalies
* Reduced height (but not dwarfism)
* Narrow cone-shaped thorax
* Hearing loss
Cleidocranial dysplasia
26
What are the skull and clavicular anomalies of cleidocranial dysplasia that are externally visible?
* Large head and small face
* Hypermobile shoulders
27
What is the lifespan of someone with cleidocranial dysplasia?
Normal life span
28
If a patient's radiographs of the thorax present the following, what is the diagnosis?
* Absent (10%) or hypoplastic clavicles
* Pseudoarthrosis (mid portion missing from clavicle)
* Small, winged, elevated scapulae
* Narrow, cone-shaped chest
Cleidocranial dysplasia
29
What are the imaging features of the thorax found in someone with cleidocranial dysplasia?
* Absent (10%) or hypoplastic clavicles
* Pseudoarthrosis (mid portion missing from clavicle)
* Small, winged, elevated scapulae
* Narrow, cone-shaped chest
30
Marfan syndrome involves the failure to produce normal ___
fibrillin-1 (FBN1 gene), an elastic component of connective tissue
31
What is the chance of a person with Marfan syndrome having a child with Marfan syndrome?
50% chance (autosomal dominant transmittance)
32
___% of those with Marfan syndrome have familial incidence
75% have familial incidence (25% have spontaneous mutation)
33
How common is Marfan syndrome?
1 in 10,000 people
34
What is the life expectancy of someone with Marfan syndrome?
Diminished by minimum 5 years, up to 35 years
35
What is the Beighton questionnaire?
Five questions to assess for hypermobility
36
What are the five questions of the Beighton questionnaire relating to hypermobility?
1. Can you now (or ever) place your hands flat on the floor without bending your knees?
2. Can you now (or ever) bend your thumb to touch your forearm?
3. As a child, did you amuse your friends by contorting your body into strange shapes OR could you do the splits?
4. As a child or teenager, did your shoulder or kneecap dislocate on more than on occasion?
5. Do you consider yourself double-jointed?
37
What is the meaning if someone answers 'yes' to 2 or more questions of the Beighton questionnaire?
High probability of hypermobility
38
What is a Beighton score?
A tool to assess for hypermobility (point system)
39
What Beighton score would mean probable hypermobility?
4 or more
40
The 9 points of the Beighton score are made up of:
* One point if, while standing and bending forward, they can place palms on the ground with legs straight
* One point for each elbow that extends more than 10 degrees
* One point for each knee that extends more than 5 degrees
* One point for each thumb that, with the wrist flexed, can be manipulated to the forearm
* One point for each fifth finger that passively hyperextends beyond 90 degrees
41
If a patient presents with the following, what is their Beighton score?
* One elbow extends more than 10 degrees
* Both knees extend more than 5 degrees
* Each fifth finger passively hyperextends beyond 90 degrees
5 (probable hypermobility)
42
If a patient presents with the following, what is their Beighton score?
* Standing and bending forward, patient can place their palms on the ground with legs straight
* With wrist flexed, each thumb can be manipulated to the forearm
3 (probably not hypermobile)
43
How does the typical Marfan syndrome patient appear?
Tall and slender; equally male and female with no racial predominance
44
Which systems are involved in Marfan syndrome?
* Anything with connective tissue
* Skeletal (mainly extremities)
* Ocular
* Cardiovascular
45
What are the ocular clinical features of Marfan syndrome?
>50% have dislocation of lens
46
___% of those with Marfan syndrome have a congenital heart disease
33%
47
Congenital heart disease results in ___% of deaths for those with Marfan syndrome
95%
48
What congenital heart abnormality is most likely to be present in someone with Marfan syndrome?
Atrial septal defect
## Footnote
33% have a congenital heart abnormality
49
What are some cardiovascular consequences of Marfan syndrome?
* Aortic dissection and rupture
* Pulmonary artery rupture
* Aortic valve incompetence
* Mitral valve prolapse
## Footnote
33% of those with Marfan have a congenital heart abnormality
50
The following are all results of which hereditary disease?
* Aortic dissection and rupture
* Pulmonary artery rupture
* Aortic valve incompetence
* Mitral valve prolapse
Marfan syndrome
51
___% of those with Marfan syndrome have scoliosis
>50%
52
What are some imaging features of elongated extremities in someone with Marfan syndrome?
* Arachnodactyly
* Thin gracile bones
* Thin cortices
* Delicate trabecular pattern
53
What is pectus excavatum?
Breastbone is depressed or sunken into the chest
54
What is pectus carinatum?
Breastbone and ribs are pushed outward
55
What are some imaging features of Marfan syndrome?
* Scoliosis
* Elongated extremities
* Pectus excavatum
* Pectus carinatum
56
If a patient's imaging presents the following, what is the diagnosis?
* Scoliosis
* Elongated extremities with thin, gracile bones
* Pectus excavatum or carinatum
Marfan syndrome
57
What are some treatments for Marfan syndrome?
* Cardiology and ophthalmology consultations
* Orthopedic surgery
* Managed symptomatically
* Relative contraindication to manipulation
58
Which gene is affected by osteogenesis imperfecta?
COL1A1 or COL1A2 (autosomal dominant)
59
How are genotypes of osteogenesis imperfecta classified?
Sillence classification (Type I-IV)
60
What are the phenotypes of osteogenesis imperfecta?
* OI congenita
* OI tarda
61
Osteogenesis imperfecta is a defect in ___ synthesis
type 1 collagen
62
The following are clinical manifestations of which hereditary disease?
* Congenital osteoporosis
* Blue sclera
* Conductive hearing loss
* Severe dental problems
Osteogenesis imperfecta
63
What are the clinical manifestations of osteogenesis imperfecta?
* Congenital osteoporosis
* Blue sclera
* Conductive hearing loss
* Severe dental problems
64
The following are radiographic features of which hereditary disease?
* Mild to severe generalized osteopenia
* Multiple fractures in various stages of healing
Osteogenesis imperfecta
65
What are the radiographic features of osteogenesis imperfecta?
* Mild to severe generalized osteopenia
* Multiple fractures in various stages of healing
66
Marble bone disease, chalk bones, Albers-Schonberg disease are all old names for ___
osteopetrosis
67
There are ___ forms and ___ different genes implicated in osteopetrosis
2 forms and 10 different genes implicated
68
What are the two forms of osteopetrosis?
* Autosomal dominant - mild form (still decreased lifespan)
* Autosomal recessive - lethal form
69
What is osteopetrosis?
Disease of decreased osteoclastic function (increased bone density)
70
The following are clinical features of which hereditary disease?
* Possible growth disturbances
* Facial palsies
* Neurogenic hearing loss
* Dental caries
Osteopetrosis
71
What are the clinical features of osteopetrosis?
* Possible growth disturbances
* Facial palsies
* Neurogenic hearing loss
* Dental caries
72
The following are radiographic features of which hereditary disease?
* Increased bone density
* Sandwich vertebra
* Erlenmeyer flask deformities
Osteopetrosis
73
The following are all complications of which hereditary disease?
* Pathologic fracture
* Anemia (increased infection risk)
* Thrombocytopenia (hemorrhage risk)
* Hepatosplenomegaly
* Blindness/deafness/facial nerve palsies
* Leukemia and sarcomas
Osteopetrosis
74
What are possible complications of osteopetrosis affecting blood?
* Anemia (increased infection risk)
* Thrombocytopenia (hemorrhage risk)
* Leukemia (cancer of blood cells)
* Sarcomas (of blood vessels)
75
What are possible complications of osteopetrosis affecting bones?
* Pathologic fracture
* Sarcomas (within bone)
76
What are possible complications of osteopetrosis affecting organs and senses?
* Hepatosplenomegaly (liver and spleen)
* Blindness
* Deafness
* Facial nerve palsies
77
What are the radiographic features of osteopetrosis?
* Increased bone density
* Sandwich vertebra
* Erlenmeyer flask deformities
