Achondroplasia
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Achondroplasia
Musculoskeletal system
Pediatric musculoskeletal conditions
Radial head subluxation (Nursemaid elbow)
Developmental dysplasia of the hip
Legg-Calve-Perthes disease
Slipped capital femoral epiphysis
Transient synovitis
Osgood-Schlatter disease (traction apophysitis)
Musculoskeletal injuries and trauma
Rotator cuff tear
Dislocated shoulder
Radial head subluxation (Nursemaid elbow)
Winged scapula
Thoracic outlet syndrome
Carpal tunnel syndrome
Ulnar claw
Erb-Duchenne palsy
Klumpke paralysis
Iliotibial band syndrome
Unhappy triad
Anterior cruciate ligament injury
Patellar tendon rupture
Meniscus tear
Patellofemoral pain syndrome
Sprained ankle
Achilles tendon rupture
Spondylolysis
Spondylolisthesis
Degenerative disc disease
Spinal disc herniation
Sciatica
Compartment syndrome
Rhabdomyolysis
Bone disorders
Osteogenesis imperfecta
Craniosynostosis
Pectus excavatum
Arthrogryposis
Genu valgum
Genu varum
Pigeon toe
Flat feet
Club foot
Cleidocranial dysplasia
Achondroplasia
Osteomyelitis
Bone tumors
Osteochondroma
Chondrosarcoma
Osteoporosis
Osteomalacia and rickets
Osteopetrosis
Paget disease of bone
Osteosclerosis
Lordosis, kyphosis, and scoliosis
Joint disorders
Osteoarthritis
Spondylosis
Spinal stenosis
Rheumatoid arthritis
Juvenile idiopathic arthritis
Gout
Calcium pyrophosphate deposition disease (pseudogout)
Psoriatic arthritis
Ankylosing spondylitis
Reactive arthritis
Spondylitis
Septic arthritis
Bursitis
Baker cyst
Muscular disorders
Muscular dystrophy
Polymyositis
Dermatomyositis
Inclusion body myopathy
Polymyalgia rheumatica
Fibromyalgia
Rhabdomyosarcoma
Neuromuscular junction disorders
Myasthenia gravis
Lambert-Eaton myasthenic syndrome
Other autoimmune disorders
Sjogren syndrome
Systemic lupus erythematosus
Mixed connective tissue disease
Antiphospholipid syndrome
Raynaud phenomenon
Scleroderma
Limited systemic sclerosis (CREST syndrome)
Musculoskeletal system pathology review
Back pain: Pathology review
Rheumatoid arthritis and osteoarthritis: Pathology review
Seronegative and septic arthritis: Pathology review
Gout and pseudogout: Pathology review
Systemic lupus erythematosus (SLE): Pathology review
Scleroderma: Pathology review
Sjogren syndrome: Pathology review
Bone disorders: Pathology review
Bone tumors: Pathology review
Myalgias and myositis: Pathology review
Neuromuscular junction disorders: Pathology review
Muscular dystrophies and mitochondrial myopathies: Pathology review
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Achondroplasia
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Content Reviewers
Rishi Desai, MD, MPHContributors
Tanner Marshall, MS
In HBO’s adaptation of Game of Thrones, the character Tyrion Lannister is treated poorly by his father and siblings because he is born with dwarfism.
In a classic scene in the show, he says [“I’m guilty of being a dwarf! [father says: You’re not on trial for being a dwarf] Oh! Yes I am, I’ve been on trial for that my entire life].
Both Tyrion and his real-life counterpart—Peter Dinklage—have achondroplasia, an autosomal dominant genetic condition which is the most common cause of dwarfism and results from a heterozygous mutation in a gene called FGFR3, or fibroblast growth factor receptor 3, on chromosome 4, which codes for FGFR3 protein.
When FGFR3 protein binds fibroblast growth factors, or FGFs, it slows down the growth of certain bones.
The mutation causing achondroplasia is almost always the 380th amino acid, which is glycine, getting swapped out for arginine in the FGFR3 protein, and this swap causes the FGFR3 receptor to be constitutively active, which means constantly, active.
In other words, the mutation makes the receptor behave as though it’s binding an FGF even when it’s not, which sends a strong signal to inhibit bone growth.
More specifically, FGFR3 that is “always on” causes chondrocytes at the growth plate to proliferate slowly and become disorganized.
So, because of this it mostly affects endochondral bone formation, which is the process of bone forming right on previously-laid-down cartilage matrix, which causes the bone to elongate.
With the mutation though, this elongation is inhibited, which means long bones like the humerus and phalanges are affected.
Alright so the mutation affects endochondral bone formation, but bones that are products of intramembranous bone formation are way less affected.
This is where bone grows without an existing cartilage matrix.
This includes flat bones like the skull and ribs. Also an intramembranous process is appositional growth, which is the process of widening of long bones, so that happens pretty normally too.
Sources
- "Robbins Basic Pathology" Elsevier (2017)
- "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
- "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
- "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
- "Achondroplasia" The Lancet (2007)
- "Distraction Osteogenesis of the Lower Extremity in Patients With Achondroplasia/Hypochondroplasia Treated With Transplantation of Culture-Expanded Bone Marrow Cells and Platelet-Rich Plasma" Journal of Pediatric Orthopaedics (2007)
- "Achondroplasia: pathogenesis and implications for future treatment" Current Opinion in Pediatrics (2010)
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