Genetic Diseases of Bone Flashcards
Cleidocranial Dysplasia
-Disorder of bone _______
-_____/______ clavicles
-Delayed closing of _____
-_______: Reduced bone density
-_______: weak bones
-______ is the mutated TF that commits Mesenchymal cells to an _______ lineage. Expressed in all stages of _____ development, and late stages of _____ development
Phenotypes:
-_______ teeth that do not erupt, and will be removed if they cause a ______ or impair existing _____
-Mice that lack this gene only have ______ and no _____ development, and will completely lack ______
- This disorder is due to the impaired ___ ___ differentiation
- Development
- Absent/Underdeveloped
- Osteopenia
- Osteoporosis
- RUNX2; Osteoblastic; bone; tooth
- Supernumerary; pathology; dentition
- Cartilage; bone; teeth
- Stem cell
Achondrodysplasia
- Disorder of _________
- _______ are disproportionately short
- Large _______ proportionally to their body size and normal _____ size
- Defect in _________ ________, this impairs the growth of _____ bones, but the normal formation of the head, pelvis, and hips
- ______ ___ ____ ______ __(______): Gene mutated that will normally stop chondrocyte ______ in order to promote differentiation into _____
- Ossification
- Limbs
- Head; normal
- Endochondral Ossification; long
- Fibroblast Growth Factor Receptor-3 (FGFR3); proliferation; bone
Fibrous Dysplasia
-Disorder of ___ ___ differentiation, like _______ ______
-______ mutation in GNA gene that is not _____. Is a GPCR that results in the overproduction of _____ that activates ____, converting it from a proto-oncogene to an oncogene. Enhancement of improper bone ____ leading to a defect in morphology
-Prevents the transition of bone-forming ______ cells to mature ______ cells
-_______: Occurs later in development only effecting one bone, typically _____ severe.
Signs include early _____ in young girls, and the development of ______ hair in young boys
-______: Occurs earlier in development affecting many bones, typically _____ severe
-_______ ______ (____): Polyostotic Fibrous Dysplasia with endocrinopathies
-_______ or _______ involvement in 25% of all Fibrous Dysplasia & 35% of patients with MAS
- Stem Cell; Cleidocranial Dysplasia
- Somatic; inheritable; cAMP; c-Fos; growth
- Progenitor; Osteogenic
- Monostotic; less; Menstruation; pubic
- Polyostotic; more
- McCune-Albright Syndrome (MAS)
- Maxillary; Mandibular
Osteogenesis Imperfecta
-Disorder of bone ______, caused by defects in ______ production
-Genetically ______
- Skeletal _____ that greatly increases fracture risk
- Typically break all their ______ when passing through the _____ _____
-Defects in either ________ Collagen synthesis or the ______ regulating it
-____% of patients have mutations in ______ Collagen genes: ______/_______, preventing it from being ______
Phenotypes:
- Bone _______
-Reduced bone _____, _____, and ______
-Deformation when weight is applied to the ____, often resulting in _______ legs
- Integrity; ECM
- Heterogeneous
- Fragility
- Bones; Birth Canal
- Type I; proteins
- 90%; Type I; COL1A1/COL1A2; mineralized
- Fractures
- Size; mass; strength
- Bones; bowed
Classification of Osteogenesis Imperfecta
- _______: Collagen defect in terms of quantity with mild to non-deforming phenotypes
- _______: Collagen defect in structure that is phenotypically Perinatally lethal
- _______: Collagen defect in structure that is phenotypically progressively deforming
- _______: Collagen defect in structure that is phenotypically moderately deforming
- Type I
- Type II
- Type III
- Type IV
Other Locations of _____ Collagen Impacted by Osteogenesis Imperfecta
- ______ causing lax _____/arthritis
- ______ causing blue-gray sclera, one of the first signs of the disease
- ______ causing hearing loss
- ______ making it more stiff/less elastic
- Teeth causes the disease ______ ______: Yellow, orange, or greyish colored teeth. Type _ is always associated with ____ phenotype, while Type _ is only associated with the ______ phenotype
- Type I
- Joints; joints
- Eyes
- Ears
- Skin
- Dentinogenesis Imperfecta; Type I; bone; Type II; dental
Hypophosphatasia -Disorder of bone \_\_\_\_\_\_\_\_\_, that effects bone & \_\_\_\_\_\_\_ -Mutations in the \_\_\_\_\_ gene, reducing the tissue non-specific form of \_\_\_\_\_ \_\_\_\_. Can cause both a \_\_\_\_\_\_\_ defect, and a \_\_\_\_\_\_\_ defect that is more severe -Highly \_\_\_\_\_\_ clinical presentation 6 Clinical Subtypes: 1) \_\_\_\_\_ lethal 2) \_\_\_\_\_ benign 3) \_\_\_\_\_ 4) \_\_\_\_\_ 5) \_\_\_\_\_ 6) \_\_\_\_\_ HPP -The older the onset the \_\_\_\_\_ severe, but the younger the onset the \_\_\_\_\_ severe
- Mineralization; cementum
- ALP; Alkaline Phosphatase; quantitative; qualitative
- Variable
1) Perinatal
2) Perinatal
3) Infantile
4) Childhood
5) Adult
6) Odonto - less; more
- ______ ______: a membrane bound Phosphomonoesterase that converts ______ to phosphate
- At least ____ isoenzymes, and TNSALP is abundant in the ______, ______, & ______ contributing to ____% of all serum ALP activity
- Essential for the catabolism of inorganic _________ to phosphate
- Phosphate is needed for ______ crystal formation, but __________ blocks _______ crystal formation preventing mineralization
- _______ is deposited along ______ fibrils and is contained within _______ vesicles
- Alkaline Phosphatase; Pyrophosphate
- 4; kidney; liver; bone; 95%
- Pyrophosphate
- Hydroxyapatite; Pyrophosphate; Hydroxyapatite
- Hydroxyapatite; Collagen; matrix
Pathogenesis of Hydrophosphatasia - Accumulation of \_\_\_\_\_\_\_\_\_ -Inhibits \_\_\_\_\_\_ of calcium/phosphate crystals, limiting \_\_\_\_\_\_ crystal formation within \_\_\_\_\_\_ vesicles Results of limited \_\_\_\_\_ mineralization: -Bone remains \_\_\_\_\_ - \_\_\_\_\_\_\_\_\_ fractures - Premature \_\_\_\_\_ loss
- Pyrophosphate
- Nucleation; Hydroxyapatite; matrix
- Matrix
- Soft
- Spontaneous
- Tooth
Manifestations of Hydrophosphatasia
- Enlarged pulp ______ and _____
- Inadequate _______ production leading to teeth spontaneously ______
- All clinical forms of HPP are associated with premature loss of ______ teeth
- Chambers; canals
- Cementum; exfoliating
- Deciduous
Osteopetrosis
- Disorder of bone _______/_______
- Defects in ________ resorption
- ________: Maintain bone quality & homeostasis
- Result of _____ failure, that are responsible for degradation of the bone matrix
- Genetically _________
- Adult form is called _________ _______
- Bone becomes ______, ______, & ______ making it more brittle and prone to ______
- _______ vertebrae, this is almost pathoneumonic for Osteopetrosis
- ________ nerve entrapment, as foramina shrink in _______ squeezing the nerves
- No _______, can only help the _______
- One of the first dental signs can be extremely dense _________ or _______
- Remodeling/Homeostasis
- Osteocytes
- Osteoclast
- Heterogeneous
- Albert-Schonberg Disease
- Thick; dense; sclerotic; fractures
- Sandwich
- Cranial; diameter
- Treatment; symptoms
- Mandible; maxilla
Paget Disease
- Disorder of bone _______/________
- A _______ disease caused by mutations in the _______ gene, but is NOT inheritable, and ________ factors
- _______ defect in bone _____ that won’t effect every bone in the body
- Shows ______ bone expansion that makes the bone larger, but this process takes _______ and is not _____
- Can be Monostotic or ______, depending on onset, _______ onset being more severe
- Remodeling/homeostasis
- Multifactorial; SQTSM1; environmental
- Focal; remodeling
- Symmetrical; years; treatable
- Polyostotic; younger
Characteristics of Paget’s Disease
- ______ become widely spaced overtime
- Increased ________ activity, this increase ______ number, size, and ______. Resulting in _______ new bone formation, but is abnormal in appearance.
- _____ _____: Blue lines histologically that indicate active bone remodeling
- ________ levels of Alkaline Phosphatase, this increases the level of Phosphate to counter the rising ________ levels
- Increased _____ bone metabolites
- Teeth
- Osteoclastic; Osteoclast; nuclearity; increased
- Reversal lines
- Increased; Calcium
- Urinary
