Orthopedic Syndromes/Disorders Flashcards
Marfans:
Genetics?
Non-op mgmt? BB for MV prolapse and Aortic dilation, routine Echo, Eye exams
Surgical indications? sciolosis and pes planovalgus, less common progressive protrusio acetabuli.
Pre op eval: echo, MRI for dural ectasia
Surgical complications:
- Spine: higher risk of junctional kyphosis, higher pseudoarthosis and revision rates.
Genetics: AD, fibrillin 1
Scoliosis (50%), dural extasia >60%, prosusio acetabuli (15-20%), others as well.
Non-op mgmt? BB for MV prolapse and Aortic dilation, routine Echo, Eye exams
Surgical indications? sciolosis and pes planovalgus, less common progressive protrusio acetabuli.
Pre op eval: echo, MRI for dural ectasia
Surgical complications:
- Spine: higher risk of junctional kyphosis, higher pseudoarthosis and revision rates. In comparison to AIS, there is a higher risk of fixation failure, infection, pseudoarthrosis, dural tear/csf leak (8%), and curve decompensation and need for reoperation
Larsen’s Syndrome
- mutations in filamin B (AD) and carbohydrate sulfotransferase 3 deficiency (AR), that presents with characteristic findings of ligamentous hyperlaxity, weird flattened face, cervical kyphosis, and multiple joint dislocations (Hip and Knee)
- cervical kyphosis caused by hypoplasia of cervical vertebrae, may present w/ extremity weakness secondary to melopathy
- look for bilateral knee dislocations
- look for club feet
Imaging: - AP of C spine 1st year of life for cervical kyphosis w/ subluxation
Tx: Cervical Kyphosis: PSF w/ 18 months of life to prevent neurologic deterioration if no neurologic deficitis. If neuro deficits then AP cervical decompression and fusion.
SMA
Genetics:
How to diagnose?
How does it present?
Txs?
Surgical treatments
Key concept for contractures?
- AR, survival motor neuron gene, results in loss of alpha-motor neurons in anterior horn of spinal cord.
- Telomeric gene deleation. All patients lack SMN-I protein. Severity based on number of functional copies of SMN-II
- Dx: DNA analysis (Quantitative analysis of SMN1 and SMN2) and muscle biopsy
- Presents as symmetric progressive weakness, absent DTRs, fasciculation present
- Tx: Nusinersen has been FDA approved for treatment of SMA. It is administered intra-thecally.
- Hip dislocation: Leave alone, standard of care
- Sciolosis by age 2-3 (60-90%), will need PSF with fusion to the pelvis address hip contractures before PSF to ensure seating balance. lower lumbar spine laminectomy to allow for nusinersen.
- Combined PSF with anterior rlease/fusion: typically not necessary due to high flexibility of curve, for curves >100 if needed
- The key concept is that contractures causing pain or limiting function can be managed surgically. Difficulty in shoeing or hygiene issues are other indications for surgical management of limb and foot deformities.
Mutations in the survival motor neuron 1 (SMN1) gene on chromosome 5q cause deficiency of the SMN protein, resulting in progressive loss of alpha-motor neurons in the anterior horn of the spinal cord and progressive weakness. Hypotonia with progressive, symmetric, proximal more than distal muscle weakness that spares the facial muscles but often has bulbar involvement. DNA analysis Quantitative analysis of SMN1 and SMN23
Multiplex ligation–dependent probe amplification
Quantitative polymerase chain reaction
Next-generation sequencing
Surgical treatment generally is considered for patients older than 4 years with a curve greater than 50°; however, this remains controversial.
Nusinersen must be administered via an intrathecal route because it does not cross the blood-brain barrier to act on the anterior horn cells. Nusinersen is an antisense oligonucleotide that alters the splicing of SMN2 messenger RNA and increases the amount of functional SMN protein produced. Nusinersen is more effective in patients with infantile and childhood-onset SMA. A loading dose is administered, followed by three doses annually for life. The 1-year cost of nusinersen is $750,000, with a subsequent cost of $125,000 per injection. Recently, a subcutaneous intrathecal catheter system was developed to allow for repeated outpatient dosing, even in patients with spinal instrumentation.
SMA relation between PFT scores and scoliosis
10 deg curve progress per year
Inverse relationship between PFT and severity of scoli w/ everly 10deg increase correlated 2.3% decrease oin peak flox and 4.7% predicted vital capacity
Scoliosis Surgical indications for SMA, what are the outcomes?
Cobb angle greater than 50° that is progressive, causing pain, contributing to poor sitting balance, causing decubiti, or causing thoracic insufficiency syndrome
- Other surgical factors include declining respiratory function, parasol rib deformity, hyperkyphosis, pelvic obliquity, truncal imbalance, and impairment of functional mobility.
- Classic literature reports improvement in postoperative peak flow and vital capacity with a slower loss of pulmonary function in patients with SMA after arthrodesis.
What gene is implicated in spinal muscular atrophy?
Which gene correlates with severity of disease in spinal muscular atrophy (SMA)?
Deletions in the SMN-I gene are found in 95% to 98% of patients with spinal muscular atrophy. Genetic testing is typically part of the diagnostic workup for spinal muscular atrophy. A positive test result is diagnostic, and, in most cases, eliminates the need for muscle biopsy.
SMA is caused by a deficiency in SMN protein. Deficiency of SMN protein leads to progressive loss of anterior horn cells and progressive muscle weakness. The severity of disease is directly related to the amount of reduction in circulating levels of SMN proteins, which are encoded by 2 alleles of the SMN1 gene and multiple copies of the SMN2 genes on chromosome 5. Affected patients with all types of SMA will have functional loss of both SMN1 genes, so this does not differentiate disease severity. Disease severity depends on the number of functional copies of SMN2 that remain. Patients with SMA1 have only 1 functioning SMN2 gene, whereas the milder forms, SMA types 2 and 3, have multiple copies that produce higher levels of SMN protein. The other choices are not associated with spinal muscular atrophy. Defects in PMP22 are the cause of 70% to 80% of cases of Charcot-Marie-Tooth disease. Mutations in the dystrophin gene cause Duchenne muscular dystrophy.
Duchenne Muscular Dystrophy
- Xlinked recessive mutation absence of dystrophin protein, Xp21.2 dystrophin gene defect due to point deletion and nonsense mutation
- young males only, 2-6 age onset
- growler sign: rsied by walking hands up legs to compensate for gluteus max and quad weakness.
- markedly elevated CPK levels (10-200x normal)
- muscle biopsy showing absent dystrophin
- DNA testing: absent or near absent dystrophin
- Echo for dilated cardiomyopathy
- scoliosis: curve progressive rapidly from 13-14: progresses w/ general kyphisis and scolios w/ varying degrees of pelvic obliquity as opposed to lodsis normally seen in idiopathic sciolisis
- Tx: Corticosteroids: prenisone, deflazacort: significant positive effect on disease progression. prednisone/deflazacort decreases rate of scoliosis requiring fusion from 92% to 20%
- ACE-I, BB for HF/cardiomyopathy, regular echo surveillance
repeated cycles of necrosis and regeneration, progressive replacement of muscle tissue with fibrous and fatty tissue.
Myopathic EMG: decrease amplitude, short duration, polyphasic motor, normal conduction velocities.
Duchenne MD has what kind of foot deformity? Tx?
Equinovarus:
non-op: stretching, PT, night time AFO use
op: TAL w. posterior tib tendon transfer, toe flexor tenotomies.
Duchenne Muscular dystrophy prognosis
Unable to ambulate by 10, wheel chair by 15, death by respiratory weakness or cardiomyopathy by 20
without steroid therapy: 5, 10, 15 survival rates 100%, 72%, 27.9%
with steroids >1 yr:
- loss of ambulation delayed 3-4 years,
- 76% lower mortality rate: 100%, 98%, 77% survival rates at 5,10,15 years
what is becker’s muscular dystrophy?
Similiar to Duchenne:
* sex-linked recessive calf pseudohypertrophy is present CPK is elevated
Differences from Duchenne: differences from Duchenne’s
dystrophin protein is decreased instead of absent (due to in-frame mutation)
later onset with slower progression and longer life expectancy (average diagnosis at age 8 years compared to 2 years with Duchenne’s)
more prone to cardiomyopathy
whats the most common muscular dystrophy? pathophysiology? whats the first line screening tool? Tx?
- Duchennes MD is the most common muscular dystrophy (1:3600).
- Dystrophin links the actin cytoskeleton to membrane-bound proteins, protecting the muscle from strain-related damage during exertion.
- CK 1st line from screening
** Creatine phosphokinase levels are elevated in this patient and the mother is the carrier.* - Treatment is with (1) steroids (improves muscle strength), (2) ACE inhibitors (slow cardiomyopathy), and (3) noninvasive ventilator support (improves life expectancy).
Duchenne genetics
- absence of the dystrophin protein which is found on the Xp21 gene.
- Deletion on Xp21
- x-linked recessive
mutation in fibrillin 1
marfans
Runx2 mutation
Runx2 mutations are associated with cleidocranial dysplasia, a disorder of membranous ossification with hypoplasia or absence of the clavicle and widening of the symphysis pubis.
Colllagent type 1 mutation
Mutations of collagen type I are most often associated with osteogenesis imperfecta.
