Miller-Pediatric syndromes with orthopedic issues Flashcards
FOP
Defect in the gene encoding activin receptor type IA/activin-like kinase 2(ACVR1/ALK2), a bone morphogenetic protein type 1 (BMP-1) receptor
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Also linked to overproduction of BMP-4
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Clinical features
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Congenital malformation of the great toe (short, valgus position with an abnormally shaped proximal phalanx)
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Progressive heterotopic ossification of tendons, ligaments, fascia, and skeletal muscle, which ultimately eliminates motion of the jaw, neck, spine, shoulders, hips, and more distal joints
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Any form of trauma may precipitate new ossification.
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Also called myositis ossificans progressiva or stone man syndrome
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Treatment
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No clearly effective medical treatment
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Goal to minimize the risk of injury without compromising the patient’s functional level and independence
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Surgical excision not indicated; may precipitate new ossification
Rett Syndrome
Family of deletion mutations of the X-linked gene encoding a protein called methyl-CpG-binding protein 2 (MECP2)
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Clinical features
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Progressive impairment and stereotaxic abnormal hand movements (like those in autism)
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Manifests in girls at 6–18 months of age
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Loss of developmental milestones that is rapid and then stabilizes
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Scoliosis with a C-shaped curve that is unresponsive to bracing
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Treatment
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Spinal instrumentation must include all of the kyphosis and the scoliosis.
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Spasticity results in joint contractures, which are treated as they are in cerebral palsy.
Beckwith-Wiedemann Syndrome
Mutation of chromosome 11 near IGF gene
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Clinical features
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Organomegaly, omphalocele, and a large tongue
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Orthopaedic manifestations include hemihypertrophy with spasticity
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Spasticity is thought to be the result of infantile hypoglycemic episodes secondary to pancreatic islet cell hypertrophy
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Growth arrest may be necessary in large limb
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Predisposition to Wilms tumor (patient must be screened regularly with kidney ultrasonography)
Nail Patella Syndrome
Autosomal dominant
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The gene for nail-patella syndrome is LMX1B, located on chromosome 9
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Clinical features
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Nail deformity (present in 98% of patients) is greatest in the thumbnails and becomes less severe in the more ulnar digits.
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Absence or hypoplasia of patella, hypoplastic lateral femoral condyle, and genu valgum may all contribute to patellar instability.
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Hypoplasia of the lateral side of the elbow, cubitus valgus
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Iliac horns (conical bony projections on posterior ilia)
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Nephropathy present in up to 40% of patients
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Treatment
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There is no specific treatment for the disorder.
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The iliac horns do not affect gait and should not be resected.
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Recurrent dislocation of the patella is treated by proximal or distal realignment.
Gaucher’s Disease
Autosomal recessive lysosomal storage disease
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Deficiency of the enzyme β-glucocerebrosidase
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Results in accumulation of cerebroside in the reticuloendothelial system
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Clinical features
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Osteopenia
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Bone pain (Gaucher crisis) and bleeding abnormalities
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Hepatosplenomegaly (characteristic finding)
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Types
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Type I: most commonly in persons of Ashkenazi Jewish descent
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Type II: infantile
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Type III: chronic neuropathic
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Radiographic findings
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Metaphyseal enlargement (failure of remodeling)
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Femoral head necrosis (may be confused with Perthes disease or MED)
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Moth-eaten trabeculae, patchy sclerosis, and Erlenmeyer flask deformity of the distal femora (70% of cases)
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Treatment is supportive; enzyme replacement and bone marrow transplant are options
Niemann-Pick Disease
Autosomal recessive disorder
lipid storage disorge
Accumulation of sphingomyelin in reticuloendothelial system cells
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Occurs commonly in Jews of eastern European descent
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Marrow expansion and cortical thinning common in long bones; coxa valga also seen
Sickle-Cell Anemia
Mutation in the β-globin gene, resulting in sickle hemoglobin (HbS)
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When the cell becomes deoxygenated, HbS molecules assemble into fibers that produce a sickle-shaped red blood cell.
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Sickle cell trait: one abnormal HbS allele
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More common but less severe than sickle cell anemia (8% prevalence)
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Patient at risk for exertional sickling; treated with oxygen and hydration
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Patient also at risk for sudden death
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Clinical features
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Sickle cell disease affects 1% of African Americans
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Sickle cell crises usually begin at ages 2 to 3 years
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Caused by substance P
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May lead to bone infarctions
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Hydroxyurea has produced dramatic relief of bone in crises
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Osteomyelitis
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Salmonella infection more commonly seen than in normal population but S. aureus still most common etiology
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Differentiation of bone infarction and osteomyelitis
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Sequential radionuclide bone marrow and bone scans (crises show decreased bone marrow uptake)
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Aspiration and culture may be necessary
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Avascular necrosis of the femoral and humeral head
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Acetabular protrusion
Thalassemia
Similar to sickle cell anemia in manifestation
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Most commonly observed in people of Mediterranean descent
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Common symptoms include bone pain and leg ulceration.
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Radiographic findings
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Long-bone thinning, metaphyseal expansion, osteopenia, and premature physeal closure
Hemophilia
X-linked recessive disorder
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Hemophilia A: decreased amounts of factor VIII
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Hemophilia B: decreased amounts of factor IX
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Can be mild (5%–25% of normal amounts of factor present), moderate (1%–5% present), or severe (<1% present)
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Clinical features
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Hemarthrosis manifests as painful swelling and decreased ROM of affected joints
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Knee most commonly affected
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Deep intramuscular bleeding is also common and can lead to formation of a pseudotumor (blood cyst).
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Intramuscular hematomas can cause compression of adjacent nerves (iliacus hematoma that compresses femoral nerve).
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Radiographic findings
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Squaring of patellae and condyles, epiphyseal overgrowth with LLD
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Generalized osteopenia with resulting fractures
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Cartilage atrophy resulting from enzymatic matrix degeneration and chondrocyte death
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Treatment
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Factor VIII should be administered in the following situations (target increase shown in parentheses)
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Vigorous PT (20%)
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Treatment of hematoma (30%)
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Acute hemarthrosis or soft tissue surgery (>50%)
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Skeletal surgery (approaching 100% preoperatively and maintained at >50% for 10 days postoperatively)
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Acute treatment of hemarthrosis is crucial and should begin immediately with administration of factor VIII or factor IX
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Administration should continue for 3 to 7 days after cessation of bleeding and should be followed by PT.
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Home transfusion therapy, with the advantage of immediate treatment when bleeding occurs, has reduced the severity of the arthropathy
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Aspiration of a hemarthrosis is controversial.
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Synovectomy
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Indicated for hemarthroses that recur despite optimal medical management
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Arthroscopy has better results with motion and duration of hospitalization than does open synovectomy.
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Radiation synovectomy: useful in patients with antibody inhibitors and poor medical management
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Contracture release and osteotomies
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Total joint arthroplasty for hemophilic arthropathy
Rickets
Vitamin D deficiency
Clinical features
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Short stature
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Limb angulation (usually varus)
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Bone pain
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Causes
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Deficiency of calcium (and sometimes phosphorus), which affects mineralization at the epiphyses of long bones
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X-linked hypophosphatemic (vitamin D–resistant) rickets: defect in cellular endopeptidase (phosphate-regulating neutral endopeptidase)
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Histologic findings: widened osteoid seams and Swiss cheese trabeculae are characteristic in bone.
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Growth plate abnormalities include an enlarged and distorted maturation zone (zone of hypertrophy) and a poorly defined zone of provisional calcification.
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Radiographic findings
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Brittle bones with physeal cupping/widening, bowing of long bones, transverse radiolucent Looser lines, ligamentous laxity, flattening of the skull, enlargement of costal cartilages (rachitic rosary), and dorsal kyphosis (cat back) (Fig. 3.44)
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Treatment
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Based on the underlying abnormality (e.g., kidney, diet, gastrointestinal, and organ); see Chapter 1, Section 1
Osteogeneis Imperfecta
Defect in type I collagen (COL1A1 and COL1A2 genes) that causes abnormal cross-linking and leads to decreased collagen secretion
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Histologic findings: increased diameters of haversian canals and osteocyte lacunae, increased numbers of cells, and replicated cement lines, which result in the thin cortices seen on radiographs
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Classification
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Multiple types have been identified.
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Sillence originally described four types; now at least eight forms recognized
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Disorder probably best considered a continuum with different inheritance patterns and severity (Table 3.19).
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Clinical features
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Bone fragility (brittle wormian bone), short stature
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Scoliosis
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Tooth defects (dentinogenesis imperfecta)
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Hearing defects
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Blue sclerae in types I and II
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Ligamentous laxity
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Basilar invagination is common in more severe clinical phenotypes.
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Fractures are common.
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Healing is normal, but bone typically does not remodel
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Fractures occur less frequently with advancing age (usually cease at puberty)
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Compression fractures (codfish vertebrae) are also common.
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Olecranon apophyseal fractures more commonly seen in OI than in the general population
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Bowing results from multiple transverse fractures of the long bones and muscle contraction across the weakened diaphysis.
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Typically an anterolateral bow or proximal varus deformity of the femur develops.
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An anterior or anteromedial bow of the tibia may develop.
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Treatment
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Bracing of extremities early to prevent deformity and minimize fractures
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Sofield osteotomies—“shish kebab” osteotomies; multiple long-bone osteotomies with either fixed-length Rush rods or telescoping (Bailey-Dubow or Fassier-Duval) intramedullary rods—are sometimes required for progressive bowing of long bones.
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Fractures
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Treatment in children younger than 2 years similar to that in children without osteogenesis imperfecta
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After age 2 years, telescoping intramedullary rods can be considered.
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Bisphosphonates have been shown to decrease the number of fractures in these patients.
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Characteristic dense parallel metaphyseal bands may be seen on x-ray. Distance between bands corresponds to time between treatments.
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Iatrogenic osteopetrosis can occur with high-dose, long-term use of bisphosphonates.
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Scoliosis
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Bracing generally ineffective
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Fusion associated with large blood loss
Juvenile Idiopathic arthritis
Clinical features
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Persistent noninfectious arthritis lasting 6 weeks to 3 months and diagnosed after other possible causes have been ruled out
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Affects girls more than boys and typically manifests before age 4 years
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Can be polyarticular, pauciarticular, or systemic
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Commonly involves the knee, wrist (flexed and ulnar deviated), and hand (fingers extended, swollen, radially deviated)
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To confirm diagnosis, one of the following must be present: presence of rheumatoid factor, iridocyclitis, cervical spine involvement, pericarditis, tenosynovitis, rash, intermittent fever, or morning stiffness.
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Ophthalmology consultation with slit-lamp examination is required twice yearly because progressive iridocyclitis can lead to rapid loss of vision if left untreated.
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In 50% of affected patients, symptoms resolve without sequelae; 25% of patients are slightly disabled, and 20%–25% have crippling arthritis, blindness, or both.
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Cervical spine involvement can lead to kyphosis, facet ankylosis, and atlantoaxial subluxation.
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Lower extremity problems include flexion contractures (hip and knee flexed, ankle dorsiflexed), subluxation, and other deformities (hip protrusion, valgus knees, equinovarus feet)
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Treatment
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NSAIDS or steroids
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Disease modifying antirheumatic drugs (DMARDs)
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Methotrexate
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TNF blockers (etanercept, infliximab)
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Rituximab (chimeric anti-CD20 monoclonal antibody)
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Surgical interventions
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Joint injections and (rarely) synovectomy for chronic swelling refractory to medical management
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Arthrodesis and arthroplasty may be required for severe juvenile idiopathic arthritis
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Systemic-onset JIA (Still disease): approximately 10%–20% of patients
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Systemic involvement: can be fatal
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Diurnal fevers (rabbit-ear graph)
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Nonpruritic salmon-pink macular evanescent rash
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Lymphadenopathy, hepatosplenomegaly, serositis
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Macrophage activation syndrome (MAS)
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Cytokine storm caused by T-cell activation
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Disseminated intravascular coagulation (DIC) causes bruising and mucosal bleeding
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Causes elevated ferritin value but decreased ESR
Ankylosing Spondylitis
Systemic autoimmune spondyloarthropathy
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HLA-B27 present in 90%–95% of patients
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The antigen is also present in 4%–8% of all white Americans; thus its usefulness as a screening tool is limited.
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Clinical features
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Typically affects adolescent boys
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Asymmetric, lower-extremity, large-joint arthritis
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Heel pain
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Hip and back pain (cardinal symptoms) may develop later.
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Progressive kyphosis
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Limitation of chest wall expansion is a more specific finding than is a positive result of HLA-B27 test.
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Uveitis and iritis
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Radiographic findings
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Bilateral symmetric sacroiliac erosion followed by joint space narrowing, subsequent ankylosis, and late vertebral scalloping (bamboo spine). Radiographs typically lack sensitivity in early stages of the condition.
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Early sacroiliitis evident on MRI may allow for diagnosis far earlier than was previously possible.
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Treatment
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NSAIDs and PT mainstays of treatment
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TNF antagonists such as etanercept, infliximab, and adalimumab are used if NSAIDs are ineffective.
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Management of spinal deformity is discussed in Chapter 8, Spine.
