Developmental Bone Disorders Flashcards
Achondroplasia mechanism
Substitution mutation of an arginine for glycine in FGFR3 on chromosome 4
Achondroplasia clinical features
Foramen magnum stenosis, thoracolumbar kyphosis, spinal stenosis, genu varum (bow legged knees), short stature, trident hand
Osteopetrosis mechanism
Heritable disorder caused by a defect in osteoclastic resorption (defect in acidification of bone) leading to dense and brittle bone
Osteopetrosis clinical features
Advanced osteoarthritis, rugged jersey spine
Osteogenesis imperfecta mechanism
Generally autosomal dominant (sometimes autosomal recessive) mutation in COL1A leading to abnormal type I collagen formation, seen in areas where type I collagen is used, like bones, teeth, ligaments, and sclera
Osteogenesis imperfecta classifications
Types I-IV, with type III being the worst one
Osteogenesis imperfecta clinical features
Blue sclera, triangular faces, defective dentition, macrocephaly, scoliosis, limb deformities, joint laxity, hearing loss, growth retardation
Osteogenesis imperfecta lab findings
Microscopic analysis of collagen (would not see triple helixes), or DNA analysis for COL1A (or other associated mutations)
Osteogenesis imperfecta radiographic findings, skull
Wormian bones, enlargement of frontal and mastoid sinuses, platybasia (flattened base of the skull) with or without basilar impression
Osteogenesis imperfecta radiographic findings, thoracic cage
Fractured and beaded ribs, pectus carinatum (outward bowing of chest)
Osteogenesis imperfecta radiographic findings, pelvis and femurs
Narrow pelvis, protrusion acetabuli (head of femur trying to punch through hip socket), Shepard’s crook deformity of the femurs (coxa vera - bowed hip)
Osteogenesis imperfecta radiographic findings, spine
Compression fractures, scoliosis
Osteogenesis imperfecta radiographic findings, fractures
Typically transverse in the lower extremities, excessive callus formation and “popcorn” bones, multiple scalloped radiolucent areas with dense rims (from bisphosphate treatment), olecranon fractures
Child abuse or bone disease?
Abuse: metaphyseal corner fractures, posteromedial rib fractures, eternal, scapular, and spinous process fractures
Bone disease: long bone fractures, clavicle fractures
Osteogenesis imperfecta treatment
No cure, IV bisphosphate for a time, vitamin supplementation with calcium, phosphorus and vitamin D, surgical treatment with load sharing devices and intramedullary implants
Marfan syndrome mechanism
Heritable disorder (autosomal dominant) caused by a genetic defect in FBN-1 that leads to abnormal collagen production and disorganized elastin
Marfan syndrome clinical features
Tall stature, aortic root dilation, hypermobility, optic lens dislocation, striae
Ehlers-Danlos syndrome mechanism
Heritable collagen and elastin defects
Ehlers-Danlos syndrome clinical features
Fragile hyperelastic skin, joint hypermobility, early development of osteoarthritis and painful joint dislocations, striae
Neurofibromatosis type 1 mechanism
Autosomal dominant mutation on chromosome 17
Neurofibromatosis type 1 clinical features
Cafe-au-lait spots, neurofibromas, freckling (especially in axillae or inguinal region), optical glioma, lisch nodules, bone lesions, antero-lateral bowing of the tibia, scoliosis
Neurofibromatosis type 2 mechanism
Autosomal dominant mutation in schwannomin gene
Neurofibromatosis type 2 clinical features
Fewer peripheral neurofibromas, more intracranial lesions, especially acoustic neuromas (benign tumors on the nerve from inner ear to brain)
