Term
| What are dysostoses? Describe the lesions. They are components of what types of syndromes? |
|
Definition
localized disorders in the ossification of fetal cartilages
-isolated, sporadic lesions
-components of complex syndromes |
|
|
Term
| What are dysplasias? describe the lesions. |
|
Definition
abnormalities in the growth and maintenance of cartilage and bone
-more diffuse effects
-hundreds of different disorders |
|
|
Term
| What is another name for osteogenesis imperfect (OI)? |
|
Definition
|
|
Term
| OI is a group of __________ disorders of _________ tissue |
|
Definition
|
|
Term
| What are 6 signs and symptoms of OI? What type of inheritance pattern does it show? |
|
Definition
-bone fractures with minimal or no trauma
-short stature, based on stature of unaffected family members, often with bone deformity
-blue sclerae
-dentinogenesis imperfecta (DI)
-progressive, post-pubertal hearing loss
-family history of OI, usually consistent with autosomal dominant inheritance |
|
|
Term
| How many recognized forms of OI exist? How many genes are associated? What are the two most common types? |
|
Definition
9
mutations on 4 different genes
1 and IV |
|
|
Term
| More than 90% of individuals with OI have dominant mutations in which two genes? What do they encode for? |
|
Definition
COL1A1 (collagen, type 1, alpha 1)
COL1A2 (collagen, type 1, alpha 2)
they encode the chains of type 1 pro collagen |
|
|
Term
| Achondroplasia is a disorder of what type of inheritance? |
|
Definition
|
|
Term
| Achondroplasia is often due to why type of mutation in what gene? It can be due to advanced age in what parent? What percentage of pt's are due to de novo mutations? |
|
Definition
gain of function in the FGFR3 gene
advanced paternal age
80% |
|
|
Term
| What are 4 major phenotypic features of achondroplasia-- what is the age at onset? stature? size of head in relation to body? spinal cord issues? |
|
Definition
-prenatal
-rhizomelic short stature
-megalencephaly
-spinal cord compression |
|
|
Term
| achondroplasia is the most common cause of what? |
|
Definition
|
|
Term
| What is the duty of FGFR3? What happens when there is a dominant mutation, like in achondroplasia? |
|
Definition
-activation of FGFR3 inhibits proliferation of chondrocytes within the growth plate, which help coordinate the growth and differentiation of chondrocytes with the growth and differentiation of bone progenitor cells
-mutations cause premature inhibition of chondrocyte proliferation within the growth plate, leading to shortening long bones and abnormal differentiation of other bones |
|
|
Term
| Achondroplastic dwarfs sometime exhibit (lordosis/kyphosis). Is intelligence normal? Respiratory function? Why does hydrocephalus sometimes occur? |
|
Definition
-lordosis
-normal intelligence
-respiratory function may be compromised by obstructive apnea and brainstem compression
-hydrocephalus due to obstruction of the sigmoid sinus |
|
|
Term
| How is achondroplasia diagnosed? What is the management? |
|
Definition
-clinical features and usually confirmed by radiographic findings
-supportive management (monitor for chronic otitis media, hydrocephalus, brainstem compression, and obstructive apnea) |
|
|
Term
| If one parent is affected with achondroplasia, what is the risk of recurrence in each child? |
|
Definition
| 50% because achondroplasia is an autosomal dominant disorder with full penetrance |
|
|
Term
| What are the odds of a child having achondroplasia if both parents are affected? |
|
Definition
50% of having it
25% of having lethal homozygous achondroplasia
25% being normal stature |
|
|
Term
| What are two other disorders caused by mutations in FGFR3 besides achondroplasia? |
|
Definition
-hypochondroplasia
-thanatophoric dysplasia
-achondroplasia |
|
|
Term
| What is osteopetrosis? what is it caused by? |
|
Definition
-abnormal thickening and hardening of the bone
-abnormal fragility of the bones with partial or complete obliteration of the marrow cavities
-caused by reduced osteoclast-mediated bone resorption, leading to defective bone remodeling |
|
|
Term
| What is the most common form of osteopetrosis? |
|
Definition
| autosomal dominant osteopetrosis (ADO) |
|
|
Term
| ADO may be asymptomatic or include what other 4 problems? |
|
Definition
multiple bone fxs
scoliosis
arthritis
osteomyelitis |
|
|
Term
| Mutations in what gene are responsible for 75% of cases of ADO and 10-15% of cases of ARO? What is the function of this gene? |
|
Definition
chloride channel 7 (CLCN7)
helps to balance the acidic environment that osteoclasts use to dissolve bone |
|
|
Term
| What is reduction of bone mass without alteration in the composition of bone, leading to fractures? |
|
Definition
|
|
Term
| Disuse osteoporosis is __________. Metabolic bone disease affects the __________ skeleton. Senile osteoporosis affects all __________ people. |
|
Definition
|
|
Term
| In osteoporosis, bone resorption by osteoclasts __________ bone deposition by osteoblasts |
|
Definition
|
|
Term
| What parts of the skeleton are affected most in osteoporosis? |
|
Definition
| those with abundant trabecular bone (vertebral bodies, femoral necks, and other weight bearing bones) |
|
|
Term
| Osteoporosis due to age related changes is mostly due to decreased activity of __________. |
|
Definition
|
|
Term
| Osteoporosis due to hormal influences is do to decreased levels of __________ following __________. Elevated IL-1 and TNF leads to elevated __________, __________ |
|
Definition
estrogen
menopause
RANK
RANKL |
|
|
Term
| Osteoporosis due to physical activity is usually associated with (increased/reduced) PA |
|
Definition
| reduced PA increases bone loss |
|
|
Term
| Osteoporosis due to genetic factors: vitamin __/__________ polymorphisms account for 75% of the maximal peak bone mass achieved in any given individual. |
|
Definition
|
|
Term
| Most adolescent __________ have insufficient dietary intake of calcium which can lead to osteoporosis due to decreased calcium intake |
|
Definition
|
|
Term
| What type of fxs are extremely common in pt's with osteoporosis? What are some complications of fractures of the femoral neck, pelvis, or spine? |
|
Definition
-thoracic and lumbar vertebral
-PE and pneumonia |
|
|
Term
| Is osteoporosis difficult to diagnose? WHen can radiographs detect it? |
|
Definition
| Yes, usually asymptomatic until fractures; radiographs cannot detect until after 30-40% of bone mass is lost |
|
|
Term
| What is another name of osteitis deformans? |
|
Definition
|
|
Term
| what is paget disease? when does it occur? |
|
Definition
| abnormal osteoblast-osteoclast bone remodeling leads to a gain in bone mass, but newly formed bone is distorted and fragile. occurs in mid adulthood, increasing with age |
|
|
Term
| What is a possible cause of paget disease? |
|
Definition
| paramyxovirus infection leading to increased expression of IL-1 and M-CSF leading to activation of osteoclasts |
|
|
Term
| Does paget disease usually affect just one site or multiple? |
|
Definition
| can be either monostotic or polyostotic |
|
|
Term
| the __________ skeleton and proximal __________ are involved in as many as 80% of paget disease cases |
|
Definition
|
|
Term
| Patients with extensive polyostotic paget disease have hypervascularity which can lead to what? what type of fxs are common in their long bones? |
|
Definition
high output congestive heart failure
chalk stick fractures |
|
|
Term
| what is softening of the bones caused by vitamin D deficiency or abnormal metabolism of vitamin d? |
|
Definition
rickets and osteomalacia
(defective bone mineralization resulting in overabundant non-mineralized osteoid) |
|
|
Term
| Who does rickets affect? Osteomalacia? |
|
Definition
-growing children (derange bone growth and skeletal deformities)
-adults (remodeled bone is under mineralized; osteopenia- predisposition to fractures) |
|
|
Term
| Hyperparathyroidism is high __________ and __________ |
|
Definition
|
|
Term
| What is the catchy phrase to remember hyperparathyroidism? explain it |
|
Definition
"painful bones, renal stones, abdominal groans, psychic moans"
-osteoporosis, osteitis fibrosa cystica, "brown tumor"
-renal stones
-GI: constipation, peptic ulcer, pancreatitis, gallstones
-CNS: lethargy, depression
-Muscle weakness and hypotonia |
|
|
Term
| What is a compound fracture? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| fractured bone not aligned |
|
|
Term
|
Definition
| at site of previous disease |
|
|
Term
|
Definition
| develops over time from collection of micro-fractures |
|
|
Term
| young people often have __________ fractures with almost perfect reconstitution of the bone |
|
Definition
|
|
Term
| What is the name for ischemic necrosis with resultant bone infarction? |
|
Definition
| osteonecrosis (avascular necrosis) |
|
|
Term
| most cases of osteonecrosis occur after a __________ or __________ use |
|
Definition
|
|
Term
| WHat are the two types of infarcts? describe them. |
|
Definition
-subchondral infarct: pain during PA; often collapse and can lead to osteoarthritis
-medullary infarct: usually clinically silent unless large; usually stable |
|
|
Term
| Osteomyelitis is an acute or chronic bone infection, what type of infection is pyogenic osteomyelitis? what is the usual causative agent? how does it usually spread within the body? |
|
Definition
bacterial
staph aureus
hematogenous dissemination |
|
|
Term
| What bones are usually affected in children with osteomyelitis? adults? how does it present? |
|
Definition
-long bones
-vertebrae, pelvis, feet
-presents as acute systemic illness with fever, malaise, leukocytosis, throbbing pain |
|
|
Term
| what is the usual tx for osteomyelitis? |
|
Definition
| surgical drainage and abx |
|
|
Term
| Tuberculous osteomyelitis is due to a __________ infxn of the bone. how does it usually spread to the bone? what bones are most often affected? what is pott disease? |
|
Definition
-mycobacterial
-in 1-3% of pulmonary TB cases, the bacilli spread to the bone through the blood
-long bones and vertebrae are affected most often
-pott disease: a form of osteomyelitis with TB of the vertebral bodies; causes deformity and collapse |
|
|
Term
| What are the most common malignant tumors of the bone? |
|
Definition
| metastatic malignant tumors arising mainly in the prostate, breast, kidney, and lung |
|
|
Term
| most primary bone tumors are __________ and occur before the age of __________ |
|
Definition
|
|
Term
| bone tumors in the elderly are more likely to be malignant |
|
Definition
|
|
Term
| __________ imaging is critical in the evaluation of bone tumors, but __________ and __________ analysis are required for the final diagnosis |
|
Definition
radiologic
biopsy
histologic |
|
|
Term
| What is the most common benign tumor of the bone? |
|
Definition
|
|
Term
| What does an osteochondroma look like? |
|
Definition
| cartilage capped bony outgrowth from metaphysis of long tubular bones (exostoses) |
|
|
Term
| Osteochondromas can be sporadic or hereditary, what gene is inactivated in hereditary osteochondromas? |
|
Definition
| EXT1 or EXT2 (both copies) |
|
|
Term
| What is a malignant mesenchymal tumor that produces a cartilage matrix? |
|
Definition
|
|
Term
| what areas if the body do chondrosarcomas typically arise in? |
|
Definition
| pelvis, shoulder, and ribs |
|
|
Term
| most chondrosarcomas are low grade and do not metastasize, the high grade metastasize to the __________ and __________ |
|
Definition
|
|
Term
| what is the tx for chondrosarcomas? |
|
Definition
|
|
Term
| What is a bone producing malignant mesenchymal tumor? |
|
Definition
|
|
Term
| where are osteosarcomas found most commonly? |
|
Definition
| the long bones of teenagers and young adults, m>f |
|
|
Term
| What mutation is present in 60-70% of sporadic cases of osteosarcomas? |
|
Definition
|
|
Term
| Patients with hereditary __________ have a 1000 times greater risk of osteosarcoma |
|
Definition
|
|
Term
| how does osteosarcoma usually present? |
|
Definition
| a painful enlarging mass near a joint |
|
|
Term
| What is a codman triangle associated with osteosarcoma? |
|
Definition
| the tumor breaks through the cortex and lifts the periosteum and forms a triangle on x ray |
|
|
Term
| what is a highly malignant small round-cell tumor of bone and soft tissue? |
|
Definition
|
|
Term
| what region of what chromosome is associated with ewing sarcoma? |
|
Definition
| a translocation in the ewing sarcoma breakpoint region 1 (EWSR1) gene on chr 22 and genes in several other chromosomes |
|
|
Term
| who does ewing sarcoma most often affect? |
|
Definition
| most children or young adults, often in puberty when bones are growing rapidly |
|
|
Term
| how does a ewing sarcoma present? |
|
Definition
| presents as painful enlarging masses in the diaphyses of long tubular bones of the arms and legs (esp femur) and the pelvis |
|
|
Term
| Where do ewing sarcomas metastasize? how often? |
|
Definition
lungs and other bones
metastasis at the time of dx present in approx 1/3 of children |
|
|
Term
| what is the tx for ewing sarcoma? |
|
Definition
| surgical excision +/- radiation |
|
|
Term
| What is the most common joint disorder? |
|
Definition
|
|
Term
| osteoarthritis is __________ of the articular cartilage |
|
Definition
| degeneration (not inflammation!) |
|
|
Term
| What are the most common sites of osteoarthritis in men and women/ |
|
Definition
women: knees and hands are more common, with Heberden nodes in the fingers
men: hips are more common |
|
|
Term
| What are 3 rf.'s for osteoarthritis? |
|
Definition
increasing bone density
high estrogen levels
being overweight |
|
|
Term
| does joint fusion occur in osteoarthritis? |
|
Definition
|
|
Term
|
Definition
| the excessive biosynthesis or reduced elimination of uric acid in the body, formation of uric acid crystals in joints |
|
|
Term
| what joints are most frequently affected with gout? |
|
Definition
|
|
Term
| describe how gout presents? |
|
Definition
| pain frequently starts during the night; throbbing, crushing, or excruciating. attack may go away in several days but may return from time to time. additional attacks usually last longer |
|
|
Term
|
Definition
| accumulation of salt called calcium pyrophosphate forms crystals in the joints |
|
|
Term
| describe a pseudo gout attack? |
|
Definition
| attacks of joint swelling and pain in the knees, wrists, elbows, shoulders, and ankles are the most commonly affected. first occurs in people over 50; increases with age |
|
|
Term
|
Definition
|
|
Term
| what is suppurative arthritis? how many joints are usually affected? |
|
Definition
direct infection of a joint space by bacteria with sudden pain, redness, swelling, fever
-usually a single joint: knee, hip, shoulder, wrist, elbow |
|
|
Term
| What is lyme arthritis? what is the vector? what joints affected? |
|
Definition
cross-reactive immune response to systemic infection
-borrelia burgdorferi transmitted by deer ticks
-develops in 60-80% of untreated pt's late in dz
-large joints: knees, shoulders, elbows, ankles |
|
|
Term
| What is muscular dystrophy? What age group? |
|
Definition
| a group of genetic diseases associated with progressive degeneration of muscles usually manifesting in childhood |
|
|
Term
| Duchenne and Becker muscular dystrophy (DMD and BMD) are inherited as what type of mutations in what gene? |
|
Definition
x-linked recessive mutations in the DMD gene
DMD complete loss of function mutations and BMD by partial loss of function mutations |
|
|
Term
| DMD encodes what protein? |
|
Definition
| dystrophin (expressed predominantly in smooth, skeletal, and cardiac muscle as well as in some brain neurons) . it is a part of a large complex of sarcolemma-associated proteins that confers stability to the sarcolemma |
|
|
Term
| DMD is a progressive myopathy resulting in muscle _________ and _________ |
|
Definition
| degeneration and weakness |
|
|
Term
| pt's usually present between 3 and 5 years of age with _________/_________ |
|
Definition
|
|
Term
| what muscles does DMD usually begin with? |
|
Definition
| hip girdles and neck flexors and progressively involves the shoulder girdle and the distal limb and trunk muscles |
|
|
Term
| Most boy patients with DMD have what two very characteristic signs of the dz by 5 yoa? |
|
Definition
gowers maneuver
calf pseudohypertrophy (replacement of muscle by fat and CT) |
|
|
Term
| In DMD since the dystrophin proteins that normally stabilize the muscle cells during contraction are defective, what happens? |
|
Definition
| plasma membranes are torn apart by muscle contraction, causing death of the muscle tissue |
|
|
Term
| what do most male patients with DMD usually die of? |
|
Definition
| impaired pulmonary function by age 18 |
|
|
Term
| what is the intelligence of pt's with DMD? |
|
Definition
| IQ 1 standard deviation below the mean and nearly a third have some degree of mental retardation |
|
|
Term
| what does the age at onset and the severity of DMD in females depend on? |
|
Definition
| the degree of skewing of x inactivation |
|
|
Term
| regardless of whether they have clinical symptoms of skeletal muscle weakness, most carrier females of DMD have what? |
|
Definition
| cardiac abnormalities such as dilated cardiomyopathy, left V dilatation, and ECG changes |
|
|
Term
| how is the diagnosis of DMD made? what is the tx? |
|
Definition
-family hx and either DNA analysis or muscle biopsy to test for immunoreactivity for dystrophin
-currently there are no curative tx for DMD. objective of therapy are slowing the disease progression, maintenance of mobility, prevention, and correction of contractures and scoliosis, weight control, and optimization of pulmonary and cardiac function |
|
|
Term
| what type of therapy has shown can slow the progression of DMD for several years/ |
|
Definition
|
|
Term
| in 2/3 of cases an affected male inherits the mutation from a _________ who carries an altered copy of the DMD gene. how do the other third get it? |
|
Definition
|
|
Term
| if a mother is a carrier each son has a _________ risk of DMD and each daughter has a _________ risk of inheriting the dmd mutation |
|
Definition
|
|
Term
| Becker MD (BMD) results from mutations in the DMD gene that lead to _________ or _________ dystrophin, not a complete loss as seen in DMD pts |
|
Definition
|
|
Term
| patients are said to have BMD rather than DMD if they are still _________ at the age of 16 |
|
Definition
|
|
Term
| Since BMD is not a _________/_________ in males like it is in DMD it can be passed from fathers to their daughters |
|
Definition
|
|
Term
| in both DMD and BMD female carriers may develop _________/_________ in the absence of apparent weakness |
|
Definition
|
|
Term
| Limb-girlde muscular dystrophies are autsomal _________ usually and _________ rarely MD's |
|
Definition
|
|
Term
| in limb girdle MD weakness and wasting is usually in what muscles? |
|
Definition
| arms and legs, mainly proximal muscles; shoulders upper arms, pelvic area and thighs |
|
|
Term
| what is the intelligence with limb girdle MD? |
|
Definition
|
|
Term
| What is the most common form of muscular dystrophy that begins in adulthood? |
|
Definition
|
|
Term
| myotonic dystrophy is characterized by progressive muscle _________ and _________ with _________ |
|
Definition
wasting
weakness
myotonia (failure of muscle to relax immediately after contraction has stopped) |
|
|
Term
| What is an eye and heart disorder common with myotonic dystrophy? |
|
Definition
cataracts
cardiac conduction abnormalities |
|
|
Term
| what type of mutation is myotonic dystrophy? |
|
Definition
|
|
Term
| TYPE 1 myotonic dystrophy is common in what part of the body? what gene is effected? |
|
Definition
lower legs, hands, neck and face
-CTG trinucleotide repeat expansion in the DMPK gene (genetic anticipation: usually maternal repeat size larger in next generation -- can be paternal too) |
|
|
Term
| What part of the body does myotonic dystrophy type 2 affect? what gene is affected? |
|
Definition
neck, shoulders, elbows, hips
CCTG tetra nucleotide repeat expansion in the CNBP gene, somatic instability-- repeat size gets larger in an individual as they age.. there is no correlation between CCTG repeat size and age of onset or severity of disease |
|
|
Term
| in type 1 myotonic dystrophy, as repeat sizes get larger, what happens? |
|
Definition
| onset occurs at a younger age and the phenotype is more severe |
|
|
