Skeletal disorders Notes

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Osmosis High-Yield Notes

This Osmosis High-Yield Note provides an overview of Skeletal disorders essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Skeletal disorders by visiting the associated Learn Page.
NOTES NOTES SKELETAL DYSPLASIA GENERALLY, WHAT IS IT? PATHOLOGY & CAUSES ▪ Disorders affecting bone development CAUSES ▪ Inherited/sporadic (de novo) genetic mutation COMPLICATIONS ▪ Caused by bone malformations, depend upon affected bones SIGNS & SYMPTOMS ▪ Commonly involve growth impairment, bone malformation DIAGNOSIS DIAGNOSTIC IMAGING X-ray/CT scan/MRI ▪ Bone malformation, impaired ossification visualization ▪ Bone-age estimation Ultrasound ▪ Prenatal diagnosis TREATMENT SURGERY ▪ Bone malformation correction if warranted/ desired ACHONDROPLASIA osms.it/achondroplasia PATHOLOGY & CAUSES ▪ Genetic disorder, causes dwarfism with disproportionate short stature ▪ Relatively normal-sized torso, short limbs, normal–large head (macrocephaly) with prominent forehead (hence “disproportionate dwarfism”) ▪ Average height ▫ Biologically-male: 131cm/4’4’’ ▫ Biologically-female: 123 cm/4’ 692 OSMOSIS.ORG CAUSES ▪ Heterozygous “gain-of-function” mutation in fibroblast growth factor receptor 3 (FGFR3) gene on chromosome 4; individuals with homozygous mutation usually do not survive ▫ Mutated receptor displays “constitutive activity” (activated in ligand binding absence) → inhibits chondrocyte proliferation ▫ Endochondral ossification affected → inhibits long bone elongation (e.g. humerus, femur)
Chapter 118 Skeletal Dysplasia ▫ Intramembranous ossification less affected → relatively normal flat bone growth (e.g. skull, ribs) ▪ Autosomal dominant inheritance pattern (20%); sporadic mutation in most cases (80%) COMPLICATIONS ▪ Eustachian tube narrowing → recurrent middle ear infection ▪ Narrowing of ▫ Lumbar spinal canal → spinal stenosis ▫ Foramen magnum → cervical medullary compression ▪ Venous obstruction at sigmoid sinus → hydrocephalus ▪ Midface retrusion → obstructive sleep apnea ▪ Obesity ▪ Small flat squared iliac wings (“mickey mouse ear”) ▪ Fibular overgrowth ▪ Metaphyseal flaring: diaphysis narrowing, metaphysis widening LAB RESULTS ▪ DNA test ▫ FGFR3 mutation-positive TREATMENT SURGERY ▪ Bone malformation correction warranted/ desired SIGNS & SYMPTOMS ▪ Long bone malformations ▫ Rhizomelic (proximal) limb shortening ▫ Varus/valgus leg malformations ▫ Short metacarpals ▫ Short phalanges (brachydactyly) ▫ Trident hand (fingertips cannot touch) ▪ Flat bone malformations (less common) ▫ Enlarged head ▫ Frontal bossing (prominent forehead) ▫ Flattened nasal bridge (saddle nose malformation) ▫ Narrow foramen magnum ▫ Spinal kyphosis/lordosis DIAGNOSIS DIAGNOSTIC IMAGING Prenatal ultrasound ▪ Skull width to femur length ratio higher than normal Figure 118.1 An X-ray image of the knee of an individual with achondroplasia. There is flaring of the distal femoral metaphysis typical of the disease. X-ray/MRI/CT scan ▪ Large skull with small skull base ▪ Narrow foramen magnum, spinal canal ▪ Short, flattened vertebral bodies OSMOSIS.ORG 693
CLEIDOCRANIAL DYSPLASIA osms.it/cleidocranial-dysplasia PATHOLOGY & CAUSES ▪ AKA cleidocranial dysostosis ▪ Skeletal dysplasia ▫ Predominantly affects intramembranous ossification-derived bone development ▫ Clavicles (cleido-), skull bones (-cranial) ▪ Abnormal teeth development, delayed cranial fontanelle closure, clavicle underdevelopment/absence, distinctive craniofacial features CAUSES ▪ Heterozygous runt-related transcription factor 2 (RUNX2) gene mutation (transcription factor involved in osteoblast, chondrocytes differentiation → delayed ossification; 30% of cases are idiopathic) ▪ Autosomal dominant inheritance pattern, can be sporadic COMPLICATIONS ▪ Osteoporosis (adults) SIGNS & SYMPTOMS ▪ Dental abnormalities ▫ Supernumerary teeth (up to 13), delayed/failed permanent teeth eruption, abnormal deciduous dentition ▪ Delayed cranial fontanelle closure → soft skull areas ▪ Short stature ▪ Hypoplastic/aplastic clavicles → shoulder hypermobility ▪ Maxilla, mandibular prognathism hypoplasia ▪ Midface hypoplasia, flattened nasal bridge ▪ Frontal/parietal bossing ▪ Abnormal ear ossicles → hearing loss 694 OSMOSIS.ORG Figure 118.2 Retained deciduous teeth in the mouth of an individual with cleidocranial dysplasia. DIAGNOSIS DIAGNOSTIC IMAGING X-ray ▪ Hypoplastic/aplastic clavicles ▪ Widened fontanelles ▪ Wormian bones (multiple small bones between sutures) ▪ Frontal/parietal bossing ▪ Supernumerary teeth ▪ Supernumerary ribs ▪ Iliac bone hypoplasia ▪ Symphysis pubis widening (diastasis) ▪ Small, highly positioned scapulas LAB RESULTS ▪ Genetic testing (confirmation) TREATMENT SURGERY ▪ Bone malformation correction if warranted/ desired
Chapter 118 Skeletal Dysplasia Figure 118.3 A chest radiograph of a neonate with absent clavicles, consistent with a diagnosis of cleidocranial dysplasia. Figure 118.4 An X-ray image of the skull of a child with cleidocranial dysplasia. There is bitemporal bossing and a widened frontal fontanelle. The posterior lambdoid suture (not visible) contains multiple wormian bones. OSMOSIS.ORG 695

Osmosis High-Yield Notes

This Osmosis High-Yield Note provides an overview of Skeletal disorders essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Skeletal disorders by visiting the associated Learn Page.