Orthopedic Developmental Pathology Flashcards
Syndrome with this Triad of findings- fibrous dysplasia of bone (polyostotic), cafe-au-lait skin pigmentation, endocrinopathies (hyperfunctioing)
McCune-Albright syndrome
McCune Albright syndrome mutation
Mutation in regulatory gene (called GNAS) encoding protein of signal transduction (G-protein alpha subunit)
Mutation occurs well after fertilization (postzygotic mutation) since the disease is not vertically transmitted and lesions tend to respect midline of body
Mesenchymal stem cells (precursor pool of clasts, blasts, chondrocytes) are decreased
disorder of craniofacial development- micrognathia (abnormally small jaw), microtia (small, malformed external ear/pinna), hypoplasia (underdevelopment) of midface, cleft palate often present, downward slanting palpebral fissures
Treacher Collins syndrome
Treacher Collins gene mutation
Mutation of the gene (called TCOF1) encoding protein needed for proper control of ribosome activity
Autosomal dominant
Excessive apoptosis of neural crest cells
Mesenchymal stem cells and osteoblasts activity decreased
Skeletal abnormalities of the upper limbs usually associated with congenital heart disease
Limb abnormalities may be bilateral or unilateral, short or absent forearm, absent digits, hypoplastic clavicles
Holt-Oram syndrome (AKA heart-hand syndrome)
Holt-oram syndrome mutation
Mutation in the gene called TBX5 encoding a transcription factor called T-box 5 protein
Autosomal dominant
Early limb development involving mesenchyme progenitors of cartilage
Short stature, upper arm and thigh commonly most shortened, midface hypoplasia (small nose), frontal bossing may be present (prominent forehead)
Achondroplastic dwarfism
Achondroplasia defect in
Defective chondroblast development
Mutation in FGFR3 (fibroblast growth factor receptor 3)
Autosomal dominant or new mutations that were present in the gametes of older age fathers of normal height
More severe than achondroplastic dwarfism, most common lethal form of dwarfism
Small, underdeveloped thoracic cavity leads to respiratory insufficiency
Thanatophoric dwarfism
Thanatophoric dwarfism mutation
Mutation in FGFR3
Deformity of the foot, 1/1000 births, affected foot is usually smaller than normal
Males affected more often
50% of cases are bilateral
No additional congenital anomalies elsewhere in the body
Clubfoot
Complex structural abnormalities of clubfoot
Talus bone too small, malformed
Ultimately get varus configuration (turned inward)
Clubfoot mutation
Multifactorial
Some have mutations in transcription factors- small subset of the homeodomain type (part of the protein that binds to specific regulatory regions of the target genes)
Decreased mesenchymal cells and osteoblasts activity
Affects bones of children (weakened or softened)
Usually from prolonged vitamin D deficiency
Various skeletal changes may be present like bowing of the legs, frontal bossing of skull, chest protuberances (rachitic rosary)
Rickets
Rickets abnormality
Abnormal osteochondral junction of rickets with disorder and poor mineralization
Short stature with severe mental impairment
Occurs mainly in iodine deficient lands
Delayed and abnormal bone development
Thin, stunted limbs- poor periosteal ossification and poor enchondral ossification which leads to soft, weak epiphysial plates so you get separations or fragmentation
Skull malformations, poorly closed sutures
Cretinism
Brittle bone disease
Mutation in gene encoding collagen chain
Prone to increased childhood fractures
Osteogenesis imperfecta
Classical name of growth hormone deficiency
Short stature
Normal body proportions maintained
Pituitary dwarfism
Skeletal changes- increased osteoclastic resorption, delayed matrix mineralization, short stature (stunted growth), osteoporosis
High turnover and low turnover subtypes
Phosphate retention pathology which induces secondary hyperparathyroidism and osteoclastic activity is stimulated as a result
Renal osteodystrophy
Specific type of bone weakening in adults from vitamin D deficiency (related to rickets in children) prone to vertebral and femoral fractures
Osteomalacia
Marble bone disease
Brittle bones due to osteoclastic dysfunction (impaired acidification)
Deposited bone not remodeled, much is woven bone (technically increased bone disease- but increase of immature bone)
Osteopetrosis
Osteitis deformans that affects elderly adults
Chalkstick fracture
Gene mutation leads to increased osteoclastic activity followed by osteoblasts activity that finally burns out into a quiescent phase to get a region of abnormal bone with strange mosaic pattern under microscopy
Prone to fractures and sarcomas
Serum alkaline phosphatase levels may rise (produced by osteoblasts)
Paget disease
Form of abnormal bone growth in adults with enlarged jaw, hands, feet
Caused by a type of pituitary adenoma
Secretes growth hormone
In children, this would cause gigantism (growth plates are still growing)
Acromegaly
Growth plate fracture classification
Type 1- shear through plate, heals rapidly
Type 2- through growth plate and bone beneath it
Type 3- through growth plate and bone above it
Type 4- through growth plate and bone above and below it
Type 5- compression of plate, worst prognosis
