Bones - Developmental Disorders Flashcards
What are 2 developmental disorders due to defects in Hormones and Signal Transduction Proteins?
- Achondroplasia
2. Thanatophoric Dysplasia
How is Achondroplasia inherited?
Autosomal Dominant
What mutation causes Achondroplasia?
FGFR3 Gain of Function mutation
What are the symptoms of Achondroplasia?
Dwarfism
- Short extremities, NORMAL trunk length, enlarged head
With Achondroplasia, is there a change in the patient’s longevity, intellect or reproductive organs?
NO
Achondroplasia is a form of dwarfism. What part of their body is of normal length?
Normal trunk length
What mutation is present with Thanatophoric Dysplasia?
A different FGFR3 gain of function mutation than one that is present with Achondroplasia
What disease is the more LETHAL form of Dwarfism?
Thanatophoric Dysplasia
What dwarfism symptom can help to differentiate Thanatophoric Dysplasia?
Small chest cavity!
With Thanatophoric Dysplasia, is there a change in the patient’s longevity?
Yes – die soon after birth
What is 1 developmental disorder that is due to defects in Extracellular Proteins?
Osteogenesis Imperfecta
What is deficient with Osteogenesis Imperfecta?
Deficient Type 1 Collagen Synthesis
– usually alpha 1 or alpha 2 chains
(COL1A1/2)
What is deficient with Osteogenesis Imperfecta?
Deficient Type 1 Collagen Synthesis
What are the signs of Osteogenesis Imperfecta?
Brittle bones
Blue sclera
Hearing loss
Dental imperfections
What are the signs of Osteogenesis Imperfecta?
Brittle bones
Blue sclera
Dental imperfections
Hearing loss
There are 4 subtypes of Osteogenesis Imperfecta. Some of which have mutant collagen and some have decreased normal collagen. Which is more severe?
Mutant collagen
Rank the best -> worst prognosis of the types of Osteogenesis Imperfecta?
1
4
3
2
Type 1 Osteogenesis Imperfecta life span and when fractures present?
NORMAL life span
– Fractures decrease in frequency AFTER puberty
A patient presents with a wedge shaped face, loose joints and normal stature. What type of Osteogenesis Imperfecta do they have?
Type 1
Type 2 Osteogenesis Imperfecta involves what not being formed?
Triple helix formation does NOT happen
Type 2 Osteogenesis Imperfecta has what type of outlook?
FATAL in utero usually
A fetus has respiratory problems, severe bone deformities and a small stature. They ultimately die in utero. What type of Osteogenesis Imperfecta did they have?
Type 2
What is the treatment for Osteogenesis Imperfecta?
Surgical rodding of long bones
Fractures that occur in child abuse are similar to those seen with Osteogenesis Imperfecta. What types of fractures?
Spiral
Rib
Fractures in multiple stages of healing with no signs of trauma
What is 1 developmental disorder that is due to defects in Metabolic Pathways?
Osteopetrosis
What is deficient with Osteopetrosis?
Deficient Osteoclasts
= Decreased bone resorption
What is deficient with Osteopetrosis?
Deficient Osteoclasts
= Decreased bone resorption
Albers-Schonberg Disease is the Autosomal Dominant form of Osteopetrosis. What is its mutation and symptom severity?
MILD symptoms
– CLCN7 mutation
The Autosomal Recessive forms of Osteopetrosis involve what possible mutations are symptom severity?
SEVERE symptoms
- TCIRG1 mutations
- Carbonic Anhydrase 2 mutations
With Osteopetrosis, what changes are present with bones?
LACK medullary cavity Bulbous ends (look like erlenmeyer flasks)
With Osteopetrosis, cranial nerves can be compressed due to deficient osteoclasts. What are some symptoms?
Deafness
Optic atrophy
Facial paralysis
Besides the cranial nerve symptoms, what are the other symptoms seen with Osteopetrosis?
Fractures
Anemia
Leukopenia and infections
With what disease do bones lack medullary cavities and have bulbous ends?
Osteopetrosis
What is a group of developmental disorders due to defects in degradation of macromolcules?
Mucopolysaccharidoses - lysosomal storage diseases
Where do Mucopolysaccharides accumulate?
In Chondrocytes and extracellular space
