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422 Cards in this Set

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what is a dysostoses?
congenital malformation, realtively benign
what is a craniorachischisis?
failure of closure of spinal column and skull
*meningomyelocele - when meninges herniates
*meningoencephalocele - when meninges AND CNS herniate
inheritance of osteogenesis imperfecta?
mutation results in?
AD
*defect in synthesis of collagen type I
manifestations of osteogenesis imperfecta?
prominent skeletal malformations
joints
eyes (blue)
ears
teeth
skin
*leads to osteopenia
which form of OI is lethal?
OI type II
where is the mutation in achondroplasia?
short arm of chromosome 4
(FGF receptor 3)
consequences of the FGF receptor - 3 mutation seen in achondroplasia?
mutation causes FGF receptor 3 to be constantly activated -> this inhibits cartilage proliferation in growth plate)
phenotype of an individual with achondroplasia?
dwarfism
shortened proximal extremities
enlarged head
normal trunk length
(normal intelligence, longevity, repr. status)
osteopetrosis is due to?
mutation in gene for osteoclast formation/function
(causes net bone overgrowth and increased bone density)
what are the consequences of the following in osteopetrosis: bone lacks a medullary canal
decreased hematopoiesis
-anemia (extramedullary hematopoiesis, hepatosplenomegaly)
-neutropenia
what are the consequences of the following in osteopetrosis: small neural foramina
see nerve compression
-visual disturbance, deafness
describe the bones seen in osteopetrosis
"brittle bone disease" - bones fracture like a piece of chalk
treatment for osteopetrosis?
bone marrow transplant
describe Albers-Schonberg disease
*group of RARE genetic diseases that manifest as osteopetrosis
*variable inheritance
describe AD type II osteopetrosis
*more common benign form
*seen in adolescents/adults
*may be asymptomatic
-or see-
*repeated fractures
*mild anemia
*mild CN deficits
describe the AR malignant type of osteopetrosis
*infantile, severe, often fatal
*manifests in utero or shortly after birth
*fractures
*anemia
*hydrocephaly
(if survive into infancy - CN entrapment, death from severe anemia, infections)
what is an osteochondroma?
benign cartilage outgrowth of the metaphysis, arises from the epiphyseal cartilage(growth plate) of long bones
describe a solitary osteochondroma
*slow growing mass, diagnose in late adolescence, young adult
*often incidental finding
*painful if nerve entrapment, fracture of stalk
*usually stop growing at time of growth plate closure
describe a hereditary exostosis
multiple osteochondromas, AD inheritance
*men affected 3x>women
*underlying bones may be bowed and shortened
hereditary exostosis may have an increased risk of developing?
chondrosarcoma
describe a chondroma
* benign tumor of hyaline cartilage
* develops from rests of growth plate cartilage
* cartilage rest proliferates and slowly enlarges
what is an endochondroma?
a chondroma that lies within the medullary cavity
what is a juxtacortical or subperiosteal chondroma?
a chondroma that lies at the bone surface
are chondromas MC multiple or solitary?
solitary
are chondromas usually symptomatic or asymptomatic?
most often asymptomatic
(sometimes painful and cause pathologic fractures)
both ollier's disease and maffuci syndrome are syndromes involving?
multiple endochondromas
1. ollier's disease is?
2. Maffuci sydrome is?
1. multiple endochondromas
2. multiple endochondromas PLUS soft tissue hemangiomas
maffuci syndrome may have an increased risk of developing?
other malignancies
(ovarian carcinoma, brain gliomas)
endochondromatosis in general has a risk of what kind of transformation?
sarcomatous
in pyogenic osteomyelitis, how do most bacteria reach the bone?
hematogenous spread
80% of all cases of pyogenic osteomyelitis are caused by?
Staph aureus
virulence factors of S. aureus when it comes to pyogenic osteomyelitis?
produces receptors to bone matrix components (collagen) -> facilitates adherence to bone tissue
3 bacteria that cause pyogenic osteomyelitis that could come from a GU tract infection or IV drug abuse?
E. coli
Pseudomonas
Kelbsiells
2 bacteria causing pyogenic osteomyelitis in neonates?
Group B strep
H. influenzae
which bacteria is known to cause pyogenic osteomyelitis in sickle cell disease patients?
Salmonella
where is pyogenic osteomyelitis commonly found in diabetics?
small bones in feet
why is pyogenic osteomyelitis found in different locations depending upon the age of the patient?
vascular circulation varies with age
where is osteomyelitis MC found in neonates and why?
metaphysis, epiphysis or both
(metaphyseal vessels penetrate the growth plate)
where is osteomyelitis MC found in kids?
metaphyseal leasions
where is osteomyelitis MC found in adults and why?
epiphyses and subchondral bone
(metaphyseal vessels reuinte with epiphyseal counterparts after growth plate closure)
pathophysiology of pyogenic osteomyelitis?
*bacteria proliferate in bone
*acute inflammation
*death of osteocytes
*necrosis of bone
define:
1. sequestrum
2. involucrum
3. Brodie abscess
1. dead piece of bone
2. sleeve of reactive bone surrounding sequestrum
3. intraosseous abscess walled off by reactive bone
in infants: where does an epiphyseal osteomyelitis infection tend to spread
joint
(septic joint)
symptoms of pyogenic osteomyelitis?
variable (malaise, chills, fever, leukocytosis, throbbing pain in affected bone)
* adults - localized bone pain w/o fever
*infants - unexplained fever (more subtle)
what would be seen in an Xray of a bone with osteomyelitis?
lytic bone destruction with surrounding sclerosis
treatment for pyogenic osteomyelitis?
surgical drainage
Abx
complications of pyogenic osteomyelitis?
*acute flare-ups
*pathologic fractures
*secondary amyloidosis
*endocarditis
*sepsis
*SCC in sinus tract
*sarcoma in infected bone (rare)
1/3 of patients with TB have this bone complication
tuberculous osteomyelitis
where is tuberculous osteomyelitis MC found?
thoracic/lumbar vertebrae
(usually solitary, multifocal in AIDS)
which is more destructive: tuberculous or pyogenic osteomyelitis?
tuberculous
(extensive necrosis)
what is Pott's disease?
tuberculous osteomyelitis, with involvement of the thoracic/lumbar spine
*multiple vertebrae
*see necrosis of intervertebral discs with extension to soft tissues (causes deformities)
deformities and complications seen in Pott's disease?
*permanent compression fractures -> kyphosis
*nerve impingement -> deficits
3 complications of pathologic fractures?
tumor
osteoporosis
infection
overview of steps in fracture repair?
soft tissue callus -> provisional callus -> Bony callus
describe formation of a soft tissue callus
*hematoma forms between broken bones
*this provides a firbin mesh which seals fracture stie
*osteoprogenitor cells are activated, see osteoclast and osteoblast activity
*formation of fusiform uncalcified soft tissue (no structural support)
describe the formation of a provisional callus from a soft tissue callus
*activated progenitor cells deposit trabeculae
*mesenchymal cells differentiate in to chondroblasts -> form fibrous and hyaline cartilage
*endochondral ossification occurs
describe the formation of a bony callus
remodeled and matured provisional callus (forms along weight bearing lines)
*unstressed portions are resorbed
*medullary cavity restored
complications of fracture repair?
*delayed healing/deformed callus
*malalignment
*devitalized bone fragments
*inadequate immobilization (may result in delayed union, pseudoarthrosis)
*infection
**complications may be caused by malnutrition, vascular insufficiency, systemic disease, old age**
what is one reason that the elderly have an increased risk of osteoporosis?
*decreased osteoblastic activity
connection between physical activity and rate of bone loss?
physical activity decreases the rate of bone loss
a calcium deficiency at which time in life will put an individual at greatest risk of osteoporosis?
rapid bone growth (adolescence)
*stunted peak bone mass
changes in bone metabolism during menopause?
*estrogen deficiency leads to increased osteoclast activity (increased IL-1)
Rickets/Osteomalacia is a defect in bone mineralization due to?
liack of vitamin D or a disturbance in metabolism
(results in accumulation of unmineralized bone matrix)
manifestations of Rickets in children?
rickets - "to twist"
irregular epiphyseal growth plates around kneww and wrist (bowed legs)
what is osteomalacia and what does it result in?
undermineralized bone, results in osteopenia and fractures
what is seen upon Xray of rickets or osteomalacia?
generalized osteopenia
also, stress fractures (multiple bilateral and symmetrical liner fractures)
how is rickets or osteomalacia diagnosed?
biopsy of long bone or iliac crest
adults - wide noncalcifies matrix of newly formed bone
kids - thickened, poorly defined growth plate
metabolic bone disease is due to what parathyroid disorder?
hyperparathyroidism
(increased PTH)
what is a musculoskeletal complication of hyperparathyroidism if it is not caught early?
osteitis fibrosa cystica
1. two primary reasons for increased PTH?
2. secondary reasons for increased PTH?
1. hyperplasia or adenoma of PT gland
2. chronic hypocalcemia, renal disease, Vit. D deficiency
for osteitis fibrosa cystica, describe:
1. early stage
2. second stage
3. third stage
1. increased osteoclastic acticity - osteitis
2. resorped bone replaced by fibrosis, hemorrhage, hemosiderin, microfractures (fibrosa)
3. cystic degeneration (cystica)
what is a Brown tumor?
reparative reaction, not a true tumor
(multinucleated cells, osteoclasts, hemosiderin, fibrosis, hemorrhage)
skeletal changes due to chronic renal disease is called?
renal osteodystrophy
what are some manifestations of renal osteodystrophy?
*increased resorption of bone
*phosphate retention
(secondary hyperparathyroidism)
*delayed matrix mineralization
*otosclerosis
*growth retardation
*osteoporosis
describe osteonecrosis
avascular/ischemic necrosis
-necrosis of bone and marrow IN THE ABSENCE OF INFECTION
("aseptic necrosis")
what is Legg-Calve-Perthes disease?
osteonecrosis of the femoral head in children
where does Osgood-Schlatter's manifest?
tibial tuberosity
pathophysiology of osteonecrosis?
*initially necrosis of trabecular bone and marrow
*then see subchondral infarcts (triangular shaped necrosis with subchondral bone as its base)
*overlying articular cartilage normal
*creeping substitution (dead trabeculae serve as scaffolds for deposition of new living bone)
gross manifestatons of osteonecrosis?
intact overlying articular cartilage, underlying yellow necrotic area
micro manifestations of osteonecrosis?
*dead trabeculae with empty lacunae
*Ca++ salts due to necrotic fatty marrow
other disorders associated with osteonecrosis?
fracture
*corticosteroids
thrombosis & embolism
vessel injury
how common is Paget's disease?
very
(90% of patients >65 yrs)
MC in whites
hypothesis for the etiology of paget's disease?
slow virus infection (paramyxovirus)
two types of Paget's disease?
polyostotic (85%)
monostotic (15%)
where is polyostotic Paget's disease MC found?
pelvis
spine
skull
where is monostotic Paget's disease MC found?
tibia, ilium, femur, skull, vertebrae, humerus
(often asymptomatic)
late Xray findings for Paget's disease?
increased bone density, loss of distinction between cortex and medulla
Symptoms of Paget's?
*mild localized pain due to microfractures
*osteoarthritis
*high output CHF in polyostotic form (hypervascular bone)
Labs in Paget's disease?
elevated alk. phos.
elevated urinary hydroxyproline
Rx. of Paget's disease?
calcitonin
diphosphanates
complications of Paget's?
development of a sarcoma (osteosarcoma, malignant fibrous histiocytoma, chondrosarcoma)
5-10%
three phases/descriptions of Paget's disease?
1. osteolytic phase (excessive osteoclastic bone absorption, large osteoclasts with excessive nuclei)
2. mixed osteoclastic/osteoblastic phase (hectic bone formation)
3. osteosclerotic/burnt out phase (gain in bone mass but disordered, mosaic bone pattern, jigsaw puzzle)
describe fibrous dysplasia
localized developmental abnormality of bone forming mesenchyme, hyperfunction of mesenchymal cells, bone arrested at woven stage
3 MC locations of fibrous dysplasia?
craniofacial bones
femur
ribs
in relation to fibrous dysplasia:
1. 70% of cases are of which type?
2. 27% of cases are of which type?
1. monostotic
2. polyostotic
gender differences in monostotic fibrous dysplasia?
male=female
where does monostotic fibrous dysplasia MC manifest?
ribs, femur, tibia, jaw
what is a major difference between monostotic and polyostotic fibrous dysplasia?
monostotic - resolves after puberty
polyostotic - persists into adulthood (progression)
describe the progression of polyostotic fibrous dysplasia
recurring fractures, long bone and facial deformities
(rare malignant transformation)
what is McCune Albright syndrome?
polyostotic fibrous dysplasia + endocrinopathies
describe the manifestations of McCune-Albright syndrome
cafe-au-lait spots
precocius puberty in girls
also see endocrinopathies (sexual precocity, hyperthyroidism, pituitary adenomas w/ GH secretion, primary adrenal hyperplasia)
*skin pigmentation on same side of body as bone lesion
hypertrophic osteoarthropathy is due to a paraneoplastic syndrome. what are the three components seen?
1. clubbing of fingers
2. periostitis with new bone formation at distal end of long bones
3. arthritis
hypertrophic osteoarthropathy is MC seen with which cancer?
bronchogenic carcinoma
most bone tumors are benign in what age group and malignant in what age group?
benign - kids
malignant - elderly
clinical significance of an osteoma?
benign, rare, slow growing (little clinical significance, but may obstruct sinus cavity, impinge on brain, eye; cosmetic problem)
osteoid osteomas are MC in:
1. what age group
2. what sex?
2. what bones?
1. under 25 yrs
2. males (2:1)
3. femur/tibia (50%)
why is an osteoid osteoma so painful?
pain is caused by excess prostaglandin E2 produced by proliferating osteoblasts
(pain relief with ASA)
Xray manifestations of an osteoid osteoma?
small round lucency with variable mineralization surrounded by extensive sclerosis
Treatment for an osteoid osteoma?
excision
what is the MC primary bone tumor after myeloma?
osteosarcoma
pathophysiology of an osteosarcoma?
*malignant spindle osteoblasts produce malignant bone matrix. *arise in the metaphyseal region of long bones (60% around the knee)
*associated with p53 mutation
what would be seen upon Xray of an osteosarcoma?
large destructive lesion or blastic mass
Codman's triangle
What is Codman's triangle and what is it a result of?
triangular shadow between cortex and raised periostium (result of reactive bone formation)
clinical sx. of an osteosarcoma?
painful, rapidly enlarging mass
(fracture may be 1st symptom)
10-20% of people with osteosarcoma have what else at the time of diagnosis?
lung mets
treatment of osteosarcoma?
chemotherapy
limb salvage therapy
(5 yr survival - 70%)
what is the 3rd MC bone malignancy after myeloma, osteosarcoma?
chondrosarcoma
chrondoma may arise from?
osteochondroma
chondrosarcoma MC effects:
1. what age group?
2. what sex?
3. what sites?
1. 40 yrs +
2. men > women
3. large bones (pelvis, ribs, femur, humerus, vertebrae)
what is seen upon Xray of a chondrosarcoma?
large tumor
fluffy calcifications
what does a chondrosarcoma look like grossly?
pearly white or light blue
focal calcifications
micro characteristics of a chondrosarcoma?
malignant chonrocytes produce cartilagenous matrix
is a giant cell tumor of bone benign or malignant?
benign (but locally aggressive)
in a giant cell tumor of bone what forms the giant cells?
fusion of monunuclear cells
in relation to a giant cell tumor of bone:
1. MC age?
2. MC site?
1. 20-40 yrs
2. knee (but any bone can be involved)
treatment for a giant cell tumor of bone?
surgical curetage
(radiation only if surgery impossible)
Ewing sarcoma involves what genetic mutation?
11:22 translocation
age group affected by Ewing sarcoma?
majority <20 yrs
where does Ewing sarcoma MC arise?
medullary cavity of diaphysis of long bones (femur, tibia, humerus, fibula)
how does Ewing sarcoma present?
painful enlarging mass
*site is tender, warm, swollen
gross manifestations of ewing sarcoma?
white fleshy/necrotic
treatment for ewing sarcoma?
preop chemo
surgery
radiation
prognosis for ewing sarcoma?
ok
5 yr survival ~75%
what four carcinomas commonly metastasize to bone?
breast
lung
kidney
prostate
what are the 3 pathways of spread for metastatic cancer to bone?
1. direct extension
2. lymphatic or hematogenous spread
3. intraspinal seeding
which type of arthritis is caused by bacterial infections in general?
pyogenic arthritis
which type of arthritis is caused by mycobacterium tuberculosis?
tuberculous arthritis
which type of arthritis is a sequelae to a Group A Strep infection?
arthritis of acute rheumatic fever
which type of arthritis is caused by borrelia burgdorferi?
Lyme arthritis
pyogenic arthritis is also known as?
usual result of?
acute suppurative arthritis
(usually the result of hematogenous spread, occasionally bacteria infect joints)
what are the MC organisms in pyogenic arthritis?
Cocci (gonococcus, staphylococcus, streptococcus)
Gram neg. bacilli (E.coli, salmonella, pseudomonas)
MCC of pyogenic arthritis in children <2 yrs?
H. infuenzae
MCC of pyogenic arthritis in adults and older children?
staph aureus
MCC of pyogenic arthritis in sexually active young adults?
N. gonorrhea
(oligoarthritis - only a few joints involved)
MCC of pyogenic arthritis in sickle cell disease?
Salmonella
predisposing conditions to pyogenic arthritis?
IV drug abuse
immune deficiencies
debilitating illness
joint trauma
chronic arthritis
is pyogenic arthritis usually monoauricular or polyauricular?
mononauricular
(mainly large joints)
describe the synovial effusion seen in pyogenic arthritis
type III (septic,pus)
in pyogenic arthritis, if the culture fails to yield a common pyogen - what should we be thinking?
TB
what would be seen upon a synovial biopsy of a joint with pyogenic arthritis?
acute inflammation
(congestion, edema, neutrophilic infiltrates)
tuberculous arthritis is a complication of?
tuberculous osteomyelitis
primary TB infection
what is the MC site of tuberculous arthritis?
spine
(tuberculous spondylitis = Pott's disease)
what type of effusion would be seen in a case of tuberculous arthritis?
type III effusion (septic)
what is seen in the synovium of a joint with tuberculous arthritis?
granulomatous inflammation
(more destructive process than pyogenic arthritis - may see obliteration of the joint space, infection may erode the joint capsule)
how is tuberculous arthritis diagnosed?
tissue biopsy and culture
(see caseating granulomas and acid fast bacilli)
arthritis of acute rheumatic fever primarily effects which age group?
children
describe the arthritis seen in acute rheumatic fever arthritis
*acute onset (few wks. after group A strep URI)
*polyarticular (large joints)
*migratory
what type of synovium is seen in acute rheumatic fever arthritis?
type II (inflammatory, slightly turbid due to increased white cells, sterile culture)
lyme disease is a multisystem infection. besides the joints, what else is affected?
nervous system
heart
three manifestations/stages of lyme disease
1. erythema migrans (bullseye rash at bite site)
2. neurologic/cardiac abnormalities
3. oligoarthritis
describe the clinical features of oligoarthritis seen in lyme disease
*usually involves 1 or 2 large joints
*transient remitting migratory polyarthritis
*most resolve w/o permanent joint damage (may have chronic symmetric polyarthritis)
describe the gross anatomic changes seen in lyme disease arthitis.
resemble RA
*chronic proliferative synovitis, pannus formation
*hyperplastic "onion skin" thickening of arteriole walls
treatment for lyme arthritis?
antibiotics
what is the primary feature of RA?
progressive inflammatory synovitis
destruction of synovial cartilage
systemic affects of RA?
may affect
skin
blood vessels
heart
lungs
muscles
which sex is RA MC seen in?
females (2-3x)
where does RA begin?
small joints
*hands - MCP and PIP
*feet (MTP and IP)
larger joint involvement follows (wrists,ankles, elbows, knees)
describe the synovial fluid seen in RA
type II (inflammatory)
-increased neutrophils, low mucin
radiologic findings seen in RA?
narowing of joint space
(loss of articular cartilage, bone erosions)
describe some characteristic joint deformities seen in RA
*destruction of tendons, ligaments, joint capsules (see radial deviation of wrist, ulnar deviation of fingers)
*deformed joints with no stability, limited to no ROM
some complications of RA that may ultimately lead to fatalities?
systemic amyloidosis
vasculitis
iatrogenic effects of therapy (GI bleeding due to NSAIDs, infections due to chonic steroid use)
what can be found in the serum that helps us make the diagnosis of RA?
serum rhematoid factor (seen in 80% of cases)
-not specifically diagnostic for RA, also occurs in collagen vascular diseases, others
where are rheumatoid nodules most likely to develop?
in skin subject to pressure (ulnar forearm, elbows, occiput, lumbosacal area)
can rheumatoid nodules develop in the viscera?
YES!
(lungs, pleura, spleen, heart)
what is the characteristic histology of a rheumatoid nodule?
*central fibrinoid necrosis
*palisading epithelioid histiocytes, lymphocytes, plasma cells
the pathogenesis of RA is multifactorial. major contributing factors?
*genetics
*arthritogen (? microbial antigens)
*autoimmune (see activated CD4+ T cells, B-lymphocytes, immune complexes)
some mediatiors of joint damage?
cytokines
TNF-a
IL-1
what is the antimicrobial antigen that is thought to be arthritogenic?
parvovirus B19
the diagnosis of RA requires 4 of what?
morning stiffness
arthritis in 3 or more joints
arthritis of typical hand joints
symmetric arthritis
rheumatoid nodules
serum RF
typical radiographic changes
describe the panus found in RA
*edematous and thick hypertrophic synovium
*may invade bone at articular margin, joint capsule, periarticular soft tissue
micro characteristics of RA?
proliferative/hyperplastic synovitis
rheumatoid nodules
fibrin deposition
fibrosis
increased vascularity with hemosiderin
when is juvenile RA MC found?
which sex is it MC in?
early childhood
females (2:1)
how long must a child have arthritis before it can be classified as juvenile RA?
>6 wks
what is meant if juvenile RA is classified as:
1. oligoarthritis
2. polyarticular
3. systemic variant
1. <5 joints involved (MC)
2. >5 joints
3. equal sexes, abrupt onset of fever, skin rash, hepatosplenomegaly
how does childhood RA differ from adult RA?
oligoarthritis MC
large joints > small joints
systemic onset more frequent
NO rheumatoid nodules
NO rheumatoid factor
HAVE antinuclear antibody
how is childhood RA similar to adult RA?
similar extra-articular manifestations
similar pathogenesis
similar joint pathology
what is a group of disorders with seronegativity for RA, have an association with HLA-B27, MC seen in young men?
spondyloarthropathy
what are the 4 spondyloarthropathies?
ankylosing spondylitis
Reiter syndrome
psoriatic arthritis
enteropathic arthritis
ankylosing spondyloarthritis MC affects which joints?
axial (SI joint)
ankylosing spondyloarthritis MC affects which sex?
males
ankylosing spondyloarthritis is associated with what HLA?
HLA-B27
what is ankylosing spondylitis?
inflammation of the teninoligamentous insertion sites
*see ossification and bony outgrowths
*leads to severe spinal immobility
how do patients with ankylosing spondylitis present?
low back pain that is chronic/progressive
complications of ankylosing spondylitis?
fracture of the spine
aortitis
amyloidosis
which type of arthritis am I?
episode of non-infectious arthritis that occurs within 1 month of a primary infection elsewhere (AI rxn initiated by prior infx)
reactive arthritis
pathogen from GU system that can cause reactive arthritis?
chlamydia
GI pathogens that can cause reactive arthritis?
shigella
salmonella
yersinia
campylobacter
mechanism of LPS causing reactive arthritis?
LPS antigen stimulates an immune response - see an abrupt onset in knees and ankles which lasts about a year
what is the triad seen in reiter's syndrome?
arthritis
nongonococcal urethritis or cervicitis
conjunctivitis
"can't see, can't pee, can't climb a tree"
joint symptoms seen in reiter's syndrome?
low back pain
joint stiffness
asymmetric pattern
clinical course of reactive arthritis?
*waxes and wanes over several weeks to months
*50% have functional disability (recurrent arthritis, tendinitis, fasciitis, lumbosacral back pain)
psoriatic arthritis primarily affects which joints?
DIP of hands and feet (symmetric)
*may involve large joints or SI joints
extraarticular manifestations of psoriatic arthritis?
conjunctivitis
iritis
what is the MC form of joint disease?
OA
(intrinsic disease of articular cartilage)
where is OA commonly seen?
hips (men)
knees and hands (women)
secondary OA is due to a predisposing condition. examples?
*abnormal mechanical stressors (sprotes, congenital defects)
*underlying systemic disease (DM, obesity)
etiology of primary OA?
unknown
("wear and tear arthritis")
what is chondromalacia?
a subcategory of OA
affects patellar surface of femoral condyles of young persons (produces pain and stiffness of the knee)
what are Heberden nodes
osteophytes at the DIP joints of the fingers, characteristic in women and seen in OA
which joints in the feet are commonly affected in OA?
first carpometacarpal joints
DIP joints
besides fingers and feet: other joints that are affected in OA?
knees
hips
cervical, lumbar spine
pathogenesis of OA?
*degeneration of cartilage, weakening of cartilage network

*increased levels of IL-1, TNF, NO (appear to be responsible for cartilage changes)

*death of chondrocyte -> viable chondrocytes aggregate -> fibrillation -> parralel surface cracks -> synovial fluid fills cracks -> cracks become more vertical -> cartilage pieces break off -> loose bodies -> synovial inflammation/hypertrophy.

*eventually it's bone against bone
biochemical abnomalities seen in OA?
decreased proteoglycan content
increased water content
clinical features of OA?
moning stiffness
deep achy pain (worse w/use)
limited ROM
enlarged, tender, boggy, crepitus
when would nerve root compression be seen in OA?
when osteophytes impinge on spinal foramina
what is seen upon Xray of a joint with OA?
narrowed joint space
hypertrophied subchondral bone
subchondral bone cysts
osteophytes (peripheral bone/cartilage growths)
cause of gouty arthritis?
hyperuricemia
above what serum levels of uric acid does crystal deposition begin to ocur?
>7mg/dL
risk factors for the development of gout?
age>30 yrs
familial
etoh, obesity, thiazides, lead toxicity
uric acid is the end product of what metabolism?
purine
what are the two pathways of uric acid synthesis?
1. de novo (purines from nonpurine precursors)
2. salvage (free purine bases from breakdown of nucleic acids, HGPRT enzyme)
why does uric acid crystallize in the joints?
synovial fluid is a poorer solvent than plasma for urates
(also lower T in foot, therefore crystallize there)
characteristics of synovium seen in acute gouty arthritis?
edema
congestion
dense neutrophilic infiltrate
what happens in acute gouty arthritis when the crystals are resolubilized?
acute attack subsides
describe the clinical s/s of acute gouty arthritis
*sudden onset of excruciating pain

*extremely tender and warm joints with hyperemia
where do most cases of acute gouty arthritis occur?
first metatarsophalangeal joint (big toe)
*then see in ankles, heels, knees, wrists, fingers, elbows
chronic gouty arthritis is repetetive urate crystal deposition from acute attacks. where do these crystals MC deposit?
joints
periarticular joint tissue
(deposits become grossly visible)
describe the synovium of chronic gouty arthritis
Pannus - hypertrophy, fibrosis, inflammatory cells
(see cytokine mediated cartilage destruction and juxta-articular bone erosions -> loss of joint function)
what type of synovial effusion is seen in gout?
type IV synovial effusion
(grossly white-gray granular appearance, birefringent needle shaped crystals under polarized light)
gross appearance of chronic gout?
chalky white chunky deposits in and around joints in soft tissue
what is a tophi?
large aggregates/masses of urate crystals with surrounding inflammatory rxn. Involves articular and periarticular tissues
what is gouty nephropathy?
deposition of urate crystals in the renal medulla.

see tophi, intratubular precipitates, free uric acid crystals and uric acid renal stones
four stages of gout?
1. asymptomatic hyperuricemia
2. acute gouty arthritis (monoarticular)
3. intercritical gout (recurrent-relapsing, polyarticular)
4. chronic tophaceous gout (bone erosion)
"pseudogout" involves deposition of what kind of crystals?
calcium pyrophosphate crystals. (common in arthritic joints)
avg. age of pts affected by calcium crystal arthritis?
50 yrs or older
which areas does calcium crystal arthritis tend do affect?
menisci
intervertebral discs
knee
describe the hereditary variant of calcium crystal arthritis
symptoms early in life
severe OA
secondary type of calcium crystal arthritis is associated with what disorders?
prior joint damage
hyperparathyroidism
hypothyroidism
hypomagnesemia
DM
hemachromatosis
what type of synovial fluid is seen in calcium crystal arthritis?
group IV
(chalky white deposits)
micro - see small rectangular crystals, weakly birefringent
a synovial cyst in the popliteal space is known as?
Baker's cyst
(herniation of the synovial membrane through the posterior joint capsule due to excess fluid)
Baker's cysts are associated with?
DJD
RA
micro characteristics of a Baker's cyst?
cyst lined by synovial epithelium
treatment of a Baker's cyst?
treat cause of excess fluid
clinical s/s of bursitis?
pain, erythema, swelling of bursa
(result of chronic trauma)
gross characteristics of bursitis?
thickened, erythematous, shaggy bursal wall with fibrinous exudate
micro characteristics of bursitis?
fibrous scarring of the wall with chronic inflammation
a cystic mass near a joint capsule or tendon sheath is called?
ganglion
where are the MC sites of a ganglion cyst?
wrist and fingers
(due to overuse injury)
gross characteristics of a ganglion cyst?
small cystic mass
usually does not communicate with joint space
multilocular
fluid similar to synovial fluid
micro characteristics of a ganglion cyst?
fibrous walled cyst with no synovial or epithelial lining
what exactly herniates in an intervertebral disc protrusion?
bulging of nucleus pulposus through weakened annulus fibrosus
what exactly happens in an intervertebral disc prolapse?
rupture of nucleus pulposus through annulus fibrosus
what exactly happens in an intervertebral disc extrusion?
rupture of nucleus pulosus through annulus fibrosus
AND
posterior or anterior longitudinal ligament
which meniscus is the MC one that is torn?
medial
(sports injury in young pts)
describe a giant cell tumor of tendon sheath
*localized and well circumscribed
*MC seen in wrists and fingers
describe a pigmented villonudular synovitis
*hyperplastic papillary synovium with foam cells and hemosiderin macrophages
*MC seen in knee
*presents with pain, locking, swelling, limited ROM
metaplastic cartilage within synovial tissue is called?
chondrometaplasia
describe chondrometaplasia
*may contain bone (osteochondromatosis)
*may detach and free float in joint space
*commonly secondary to underlying disease (DJD, various arthropathies)
*usually monoarticular (knee, hip, elbow)
origins of synoviosarcoma?
unknown
(at one time thought to be derived from synovium)
where do synoviosarcomas MC occur?
around extremity joints in deep soft tissue
(lower extremity around knee/thigh)
which age group are synoviosarcomas MC seen in?
20-40yrs
in a synoviosarcoma:
1. which cells are found in the monophasic type?
2. biphasic type?
1. usally only spindle cells
2. spindle and epithelioid cells
chromosome abnormality seen in synovosarcoma?
translocation at X,18
treatment for a synoviosarcoma?
aggressive
(limb sparing therapy and chemo)
prognosis of synoviosarcoma?
10 yr. survival rate: 11-30%
common mets. to lung, skeleton, regional lymph nodes
where do the majority of soft tissue neoplasms originate?
thigh
are most soft tissue tumors benign or malignant?
benign
two MC benign soft tissue neoplasms?
lipomas
hemangiomas
treatment for benign soft tissue tumors?
excision (curative)
a malignant tumor of soft tissue is called?
sarcoma
MC sites of sarcomas?
extremities
retroperitoneum
prognosis of a low vs. high grade sarcoma?
low grade - good survival with local recurrences
high grade - usually fatal, treatment rarely successful
four components of the grade of a sarcoma?
mitoses
cellularity
anaplasia
necrosis

*grade correlates with prognosis
whic sex in general has a poorer prognosis when it comes to sarcomas?
males
sarcomas are derived from which embryonic cell type?
mesenchymal cells
MC site of occurance of a benign histiocytoma?
skin
what is the MC form of benign fibrous histiocytoma?
dermatofibroma

(mass in the dermis composed of spindle cells and collagen fibers)
benign fibrous histiocytomas are primary composed of what cell type?
spindle cells
malignant fibrous histiocytomas (MFH) MC occur in which age group?
7th decade
where do most MFHs arise?
lower extremities
gross characteristics of MFH?
multilobulated, gray-white
fleshy, infiltrative, *unencapsulated mass
hemorrhage, necrosis
5 histologic variants of MFH?
1. storiform-pleomorphic (MC, spindle cells)
2. myxoid variant (abundant myxoid stroma)
3. giant cell
4. inflammatory
5. angiomatoid
what is the most frequent soft tissue tumor?
lipoma
peak age of incidence of a lipoma?
50-60
(rare under age 20)
lipomas are MC found where?
subcutanous -> back, shoulder, neck
gross characteristics of a lipoma?
delicate capsule, poorly delineated from surrounding adipose tissue

*usually small (1-4 cm)
histo characteristics of a lipoma?
indistinguishable from normal adult fat
a liposarcoma arised from what cell type?
primitive mesenchymal cells

(NOT adult fat cells)
Not from preexisting lipomas
peak incidence of liposarcoma?
50-70
gross characteristics of a liposarcoma?
opaque, grey-white to slightly yellow
*may be myxoid, gelatinous
*multilobular
*can get big (5-10cm)
*areas of hemorrhage, necrosis, cystic softening
what is an important histo characteristic in the diagnosis of liposarcoma?
lipoblasts
(fat cells with a vacuolated cytoplasm)
liposarcomas are very aggressive. where do they metastasize to?
lungs
viscera
serosal surface
(85-90% metastasize)
where do leiomyomas and leiomyosarcomas MC occur?
female genital tract
where are fibromas MC found?
ovary (cortical fibromas)

also found along nerve trunks (neurofibromas)
are fibrosarcomas common?
NO (very uncommon - many lesions previously diagnosed as fibrosarcomas are reclassified)
where do fibrosarcomas commonly occur?
deep soft tissue
-retroperitoneum
-thigh
gross characteristics of a fibrosarcoma?
unencapsulated, infiltrative, soft tissue mass
(fish-flesh appearance, also see hemorrhage, necrosis)
micro characteristics of a fibrosarcoma?
cellular
spindle cells
herringbone pattern
prognosis of a fibrosarcoma depends on (3)?
cytologic atypia
tumor size
location
recurrence rates of a fibrosarcoma?
HIGH (>50%)

also,mets in ~25% at time of diagnosis
5 yr survival rate 60-80%
fibromatosis in neck muscles is called?
fibromatosis colli
fibromatosis of the penis is called?
Peyronie's disease
fibromatosis of the feet is called?
plantar fibromatosis
what is a Dupuytren's contracture?
fibromatosis of the palms of the hand

*irregular or nodular thickening of the palmar fascia
*may trap tendons or attach to skin
*causes flexion contractures, leads to deformity and limitation of motion
gross and histo appearance of Dupuytren's contracture?
gross - dense white fibrous tissue mass
micro - acellular or cellular nodules of fibrous tissue
which sex is MC affected by fibromatosis?
males
disease course of fibromatosis?
20-25% of the time the fibromatosis stabilizes with time or resolves spontaneously
what is a very aggressive form of fibromatosis?
desmoid tumor
(infiltrative fibrous proliferation)
where does a desmoid tumor arise from?
CT and aponeuroses of skeletal muscle
a desmoid tumor resembles a low grade ?
fibrosarcoma
peak age of incidence of desmoid tumors?
20-40
desmoid tumors MC affect which sex?
females
(esp. frequently after pregnancy - abdominal desmoid)
syndrome involving familial polyposis, osteomas, fibrosis (desmoid)?
Gardner's syndrome
gross morphology of desmoid tumors?
gray-white, firm, unencapsulated poorly demarcated masses infiltrating between muscles
histology of a desmoid tumor?
*central region - dense collagenous fibrous tissue
*may see trapped atrophic muscle fibers
*regenerative activity creates muscle giant cells
why is it important to differentiat a desmoid tumor from a sarcoma?
desmoids are curable by excision, good prognosis
describe the bimodal distribution of inflammatory myopathies
children
40-60 yrs
which sex are inflammatory myopathes MC in?
women
inclusion body myositis primarily effects which age group?
adults >50 yrs
which one, dermatomyositis or polymyositis is MC seen in both kids and adults?
dermatomyositis
chronic inflammatory myopathy is MC seen in which muscles?
proximal muscles
(symmetric)
which type of rash is commonly seen in dermatomyositis?
heliotrope rash
describe the muscle weakness seen in dermatomyositis?
slow onset muscle weakness

*affects proximal muscles first
*bilateral, symmetric
*often see dysphagia
extramuscular manifestations of dermatomyositis?
interstitial lung disease
myocarditis
vasculitis
**increased risk of visceral cancers**
describe the muscle involvement seen in inclusion body myositis
*distal muscles first
*may be asymmetric
*insidious disorder
is inclusion-body myositis associated with malignancy?
no
etiology of inflammatory myopathies?
thought to be autoimmune
*see other AI disorders
*autoantibodies are found in some cases (RF, ANA)
which antibody is found that is characteristic of inflammatory myopathy?
Jo-1 autoantibody
pathogenesis of polymyositis?
cell mediated injury
(CD8+ cytotoxic T cells and macrophages found in muscle)
what seem to be the principal targets in dermatomyositis?
capillaries
(microvasculature is attacked by antibodies and complement - results in ischemic myocyte necrosis)
where are the lymphocytic infiltrates found in:
1. PM
2. DM
1. lymphocytes found in endomysium
2. perivascular and perymisial lymphocytic infiltrates
histo characteristics of a regenerating muscle fiber?
nucleus in the middle of the muscle fiber, not on the periphery (as in a normal muscle fiber)
perifascicular atrophy is seen in which inflammatory myopathy?
DM
(probably related to a state of hypoperfusion of muscle fascicles)
4 diagnostic criteria for an inflammatory myopathy?
1. clinical findings
2. EMG findings
3. elevated serum levels of muscle related enzymes
4. muscle biopsy req'd for definitive diagnosis
describe the clinical findings necessary for the diagnosis of an inflammatory myopathy
*characteristic history of muscle weakness (proximal and symmetrical)
*muscle pain and tenderness detectable on PE
*characteristic rash for DM
describe the EMG findings indicative of an inflammatory myopathy
consistent with spontaneous activity and myopathic changes
exactly what "muscle enzymes" are elevated in inflammatory myopathies
aldolase
CPK
(reflects muscle injury and enzyme release)
therapy for inflammatory myopathies?
immunosuppressive therapy
what is the source of trichinosis?
inadequately cooked pork
pathogenesis of trichinosis?
*human ingests larvae
*cyst wall is digested, larvae released into stomach
*mature to adult worms in duodenum
*female worm deposits larvae, enter the bloodstream,
*larvae invade striated muscle
where is trichinosis MC found?
most active muscles (richest blood supply)
*diaphragm
*EOM
*extremity muscles
*intercostals
reaction of the muscle cells to Trichinella larvae penetration?
*muscle becomes collagenous capsule - "nurse cell"

*eventually larvae and host cell die

*inflammatory rxn. occurs

*fibrosis and calcification of cyst (see radiodensities on Xray)
clinical s/s seen in a trichinosis infection?
*normally mild or subclinical disease

*severe infx: vomiting, diarrhea

*hematogenous dissemination, muscular invasion (fever, myalgia, swelling, weakness)
manifestations of brain involvement in trichinella infection?
H/A
disorientation
encephalitis
where would you want to do a muscle biopsy when looking for trichinella?
deltoid
gastroc
treatment of trichinosis?
predinsone
albendazole
how common are rhabdomyomas?
extremely rare
which areas do rhabdomyosarcomas MC involve?
head and neck region
(benign - cured by local excision)
what is the MC malignancy of soft tissues in children <15 yrs of age?
rhabdomyosarcoma
what are the 3 variants of rhabdomyosarcoma?
1. embryonal
2. alveolar
3. pleomorphic
what type of rhabdomyosarcoma is the boytroid form?
embryonal
rhabdomyosarcoma has the following genetic abnormalities:
t(2;13) (35;14) and (1;13)
what is the ultimate result of these mutations?
dysregulation of muscle differentiation by chimeric PAX3-FKHR protein
in relation to an adult pleomorphic rhabdomyosarcoma:
1. where is it MC seen?
2. growth rate?
3. MC age?
1. extremities, retroperitoneum
2. extremely rapid
3. >45 yrs
gross morphology of a pleomorphic rhabdomyosarcoma?
situated deep w/i muscle

soft gray fish flesh appearance (areas of necrosis and hemorrhage)
in what age group does alveolar rhabdomyosarcoma MC occur in?
10-25 yrs
where are alveolar rhabdomyosarcomas MC seen?
lower or upper extremity
(occasionally involve trunk)
histo morphology of alveolar rhabdomyosarcoma?
undifferentiated round to oval tumor cells in small nests with a fibrovascular stroma, occasional multinucleated giant cells

**resembles alveolar pattern of lung**
characteristics of rhabdomyosarcomas in general?
HIGH GRADE MALIGNANT AGRESSIVE TUMORS
*widespread dissemination occurs early (20-40% have mets at time of diagnosis)
prognosis of a rhabdomyosarcoma?
usually death occurs w/i months
median survival: 3-5 yrs
which type of rhabdomyosarcoma has the best prognosis?
botyroid subtype
(then embryonal, pleomorphic, alveolar)
who has a better prognosis when it comes to a rhabdomyosarcoma: adults or kids?
kids (65% cured)
7 preventative interventions for osteoporosis?
1. good diet with adequate Ca++ and vit. D intake (avoid soda)
2. regular weight bearing xercise
3. quit smoking
4. loose weight if overweight
5. moderate etoh intake
6. reduce or d/c meds that predispose to osteoporosis
7. fall prevention education
what are the indications for pharmacological therapy in osteoporosis?
* postemenopausal women with a T score of <-2 and no risk factors
* T score <-1.5 if other risk factors present
* previous hip or vertebral fracture
which Ca++ supplement has the most absorbable elemental calcium?
Calcium carbonate
which two forms of calcium are better tolerated than calcium carbonate?
calcium citrate
calcium gluconate
(less GI upset)
dose of elemental Ca++ and vit. D in a postmenopausal woman?
Ca++: 1000-1500 mg/day
vit. D: 400-800 IU/day
how does an estrogen deficiency promote osteoporosis?
*osteoclasts & osteoblasts have estrogen receptors

*estrogen promotes apoptosis of osteoclasts and inhibits their function

*estrogen deficiency increases production of IL-1, IL-6 and TNF in osteoblasts. this indifectly stimulates osteoclast differentiation and production -> net increased bone resorption and bone loss
how does HRT work in increasing bone mass?
acts on osteoblasts to reduce IL-6. result is reduced osteoclast production, reduced bone resorption.
SERMs have estrogen action where (and not where)?
have action on bone and lipids
NOT on breast and endometrium
SERM of choice to treat osteoporosis?
Raloxifene (evista)
raloxifene has been shown to reduce the incidence of what kind of fractures?
vertebral
(not hip or others)
MOA of bisphosphonates?
BISPHOSPHONATES SLOW BONE TURNOVER

bound to bone mineral when administered
*slowly released as bone is resorbed, taked up by osteoclasts
*inhibits formation of ruffled border of osteoclast(where active resorption occurs)
*this inhibits osteoclast function and decreases bone resorption
connection between long term bisphosphonate therapy and bone mineral content?
increases
adverse effects of bisphosphonates?
GI
(heartburn, esophageal irritation, abd. pain, diarrhea)
patient directions for taking bisphosphonates?
*in am on an empty stomach
*must be upright
*take with 8 oz of water
*remain upright, eat nothing for 30 minutes
effects of Ca++ and antacids on absorption of bisphosphonates?
interfere (reduce absorption)
what is teriparatide (Forteo)
recombinant hPTH
what is unique about the effects of hPTH in relation to osteoporosis?
only approved therapy that stimulates bone formation rather than inhibition of bone resorption
if PTH is given continuously it has a catabolic effect. how does it work then?
when administered once per day "pulsatile secretion," it stimulates bone formation
where has hPTH been shown to increase bone mineral density?
spine
hip
(reduces incidence of vertebral and nonvertebral fractures)
adverse effects of teriparatide?
nausea, dizziness, leg cramps, H/A
*orthostatic hypotension with first few doses
*mild hypercalcemia, hypercalciuria
contraindications for teriparatide and why?
Paget's disease, unexplained elevations in serum Alk Phos, prior skeletal radiation, children or young adults with open epiphyses
INCREASED RISK OF OSTEOSARCOMA (in mice)
which osteoporosis therapy also has the benefit of analgesic properties for bone pain?
calcitonin
what are the two LETHAL osteochondrodysplasias?
Achondrogenesis II
chrondrodysplasia punctata (rhizomelic type)
physical features of achondrogenesis II?
short trunk with prominent abdomen
severe micromelia
flat midfacies
micrognathia
cleft palate
hydropic appearance
radiologic features of achondrogenesis II?
*absent or severely retarded ossification of vertebral bodies, sacrum, pubic & ischial bones
*barrel shaped thorax, short ribs
*small iliac bones
*very short tubular bones with metaphyseal flare and cupping
genetics of achondrogenesis II?
AD
mutation in COL2A1 gene
chromosome 12
what does the COL2A1 gene encode?
collagen type II apha I chain
MCC of death is chondrodysplasia punctata - rhizomelic type?
repeated infections
physical characteristics of chondrodysplasia punctata - rhizomelic type?
*rhizomelic, disproportionate short stature
*flat face with small saddle nose
*bilateral cataracts
*multiple contractures
radiologic characteristics of chondrodysplasia punctata - rhizomelic type?
*vertebral coronal clefts
*short humeri and femurs with metaphysial splaying
*punctate epiphyses at end of long bones
*abnormal grey-white matter relationship on MRI (MR)
inheritance pattern of chondrodysplasia punctata - rhizomelic type?
AR
mutations in chondrodysplasia punctata - rhizomelic type affect which genes?
PEX 7 (encodes peroxisomal targeting)
DHAPAT
alkyl-DHAP synthase
physical characteristics of metaphyseal chondrodysplasia - McKusic type?
short limb dwarfism
fine, sparse hair, eyebrows, lashes
limited elbow extension
ligamentous laxity
short, pudgy hands and feet
abnormal lab values seen in metaphyseal chondrodysplasia - McKusic type?
impaired in vitro T cell function
anemia
lymphopenia
neutropenia
radiologic abnormalities seen in infancy in metaphyseal chondrodysplasia - McKusic type?
shortened long bones
curved femurs with rounded distal ephiphyses
short ribs
anterior angulation of sternum
radiologic abnormalities seen in adults in metaphyseal chondrodysplasia - McKusic type?
shortened tubular bones
metaphyseal dysplasia of long bones
metaphyseal irregularities: knee>proximal femurs
ling fibula
inheritance pattern of metaphyseal chondrodysplasia - McKusic type?
AR
in metaphyseal chondrodysplasia - McKusic type: which gene do the mutations occur in?
RMRP gene (chromosome 9)
encodes for RNA component of a ribonucleoprotein endoribonuclease
non-skeletal manifestations of metaphyseal chondrodysplasia - McKusic type?
Hirschprung's disease
recurrent childhood infections
severe varicella rxns
increased non-Hodgkin lymphomas
normal intellectual development
what is unique about the onset of pseudoachondroplasia?
normal growth for 12-18 months, then growth retardation
physical characteristics of pseudoachondroplasia?
short-limbed dwarfism (proximal shortening)
normal head and face, long trunk
accentuated lumbar lordosis, mild-moderate scoliosis
knock knees or bowed legs
hypermobile joints (except elbows)
in relation to pseudoachondrodysplasia: mental status and life expectancy?
normal for both
radiologic abnormalities in a child with psudoachondrodysplasia?
vertebral flattening, biconvex deformity
end plate deformities
tongue-like protrusions of vertebral body central portion
radiologic abnormalities in an adult with psudoachondrodysplasia?
partial restoration of normal vertebral form
marked femoral head dysplasia
radiologic abnormalities in both children and adults with psudoachondrodysplasia?
shortening of long bones
expanded, irregular metaphyses
small, deformed epiphyses
genetics of psudoachondrodysplasia?
AD
mutation in COMP gene
(chromosome 19)
encodes cartilage oligomeric matrix protein (COMP)
what is a skeletal dysplasia with major involvement of the spine?
Diastrophic dysplasia
genetics of diastrophic dysplasia?
AR
mutation in DTDST (diastrophic dysplasia sulfate transporter)gene
*result is no cellular sulfate transportation -> production of undersulfated cartilage proteoglycans, disrupts assembly of cartilage matrix
hallmark physical manifestations of diastrophic dysplasia?
small stature, short extremities
joint contractures
hypermobile thumbs
club feet, incr. distance btwn first and secodn toes
cauliflower pinnae
cleft palate
progressive kyphoscoliosis
two skeletal dysplasias with multiple dislocations?
Larsen syndrome
dysostosis multiplex
inheritance pattern of Larsen syndrome?
both AD and AR
AD has mutation on chromosome 3
physical manifestations of Larsen syndrome?
multiple joint dislocations
craniofacial abnormalities (prominent forehead, low nasal bridge, wide spaced eyes, flat face, cleft palate/uvula)
pes equinovarus (club foot)
forefoot torsion
dysostosis multiplex is a mutation in?
GLB1 gene (encodes lysosomal enzyme B-galactosidase)
*result is complex carbohydrate storage disease (GM1 - gangliosidosis I)
physical characteristics of dysostosis multiplex?
facial edema
ascites at birth
failure to thrive
motor retardation
coarse facial features
ginvigal hypertrophy, large tongue
hepatosplenomegaly
*rarely survives 2nd yr of life
lab values seen in dysostosis multiplex?
*increased urinary excretion of galactose rich oligosaccharides
*increased urinaty keratan sulfate
*absent B-galactosidase activity
name a skeletal dysplasia with predominant involvement of a single site or segment
cleidocranial dysplasia
genetics of cleidocranial dysplasia?
AD
mutation in CBFA 1 gene
(encodes protein, part of bone morphogenetic protein signaling cascade)
physical features of cleidocranial dysplasia?
clavicular hypoplasia
small maxilla
small or winged scapulae
broad forehead, widely separated eyes
persistence of deciduous teeth, late dental erruption
spinal deformities
name a skeletal dysplasia with increased bone density and tubular undermodeling
pyknodyostosis
genetics of pyknodyostosis?
AR
mutation in CSTK (cathepsin K) gene
chromosome 1
gene encodes cathepsin K; absence causes proteolytic degradation of organic matrix by osteoblasts
physical characteristics of pyknodyostosis?
short limbed dwarfism
small face, hypoplastic maxilla
bulging eyes
beak-like nose
receding chin
persistance of primary teeth, enamel hypoplasia
short terminal phalnges
increased bone fragility