summary Spinal Muscular Atrophy is a common genetic disease caused by an autosomal recessive mutation in the survival motor neuron gene. The condition presents with progressive motor weakness, scoliosis, hip dislocations, and lower extremity contractures. Diagnosis is made by DNA analysis and muscle biopsy. Treatment involves a multidisciplinary approach to address motor weakness, scoliosis, and lower extremity contractures. Treatment of associated hip dislocation is observation. Epidemiology Incidence most common genetic disease resulting in death during childhood 1 in 10,000 live births Anatomic location progressive weakness starts proximally and moves distally Etiology Pathophysiology caused by progressive loss of alpha-motor neurons in anterior horn of spinal cord Genetics inheritance autosomal recessive mutation survival motor neuron (SMN) gene mutation present in 90% of cases of SMA a telomeric gene deletion SMN critical to RNA metabolism and is a mediator of apoptosis there are two SMN genes all patients with SMA lack SMN-I protein severity of disease based on number of functional copies of SMN-II Associated conditions orthopaedic manifestations of SMA hip dislocation and subluxation scoliosis lower extremity contractures Classification Types of Spinal Muscle Atrophy Type Name Presentation Prognosis Type I Acute Werdnig-Hoffman disease Present at < 6 months Absent DTR Tongue fasciculations Poor, usually die by 2 yrs. Type II Chronic Werdnig-Hoffman disease Present at 6-12 months Muscle weakness worse in LE Can sit but cant walk May live to 5th decade Type III Kugelberg-Welander disease Present at 2-15 years Proximal weakness Walk as children, wheelchair as adult Normal life expectancy - may need respiratory support Presentation Symptoms symmetric progressive weakness that is more profound in lower-extremity than upper extremity more profound proximally than distally Physical exam absent deep tendon reflexes distinguishes from Duchenne's muscular dystrophy where DTR are present fasciculations present Imaging Radiographs scoliosis series pelvis Evaluation Diagnosis based on DNA analysis muscle biopsy prenatal diagnosis is possible Treatment Nonoperative Nusinersen has been FDA approved for treatment of SMA. It is administered intra-thecally. Operative treat associated orthopaedic disorders (details below) hip dislocation scoliosis lower extremity contractures Hip Dislocation Overview hip subluxation and dislocation occur in 62% with type II SMA, and less frequently in Type III. Treatment nonoperative observation alone (leave dislocated) indications standard of care as dislocations typically remain painless and high recurrence rate if open reduction attempted Scoliosis Overview the development of scoliosis is almost universal usually occurs by age 2 to 3 years often progressive Treatment nonoperative bracing indications devices may delay but not prevent surgery in children younger than ten years operative PSF with fusion to pelvis indications progressive curve technique address hip contractures and any other lower extremity contractures before PSF to ensure seating balance to allow for intrathecal Nusinersen to be given after spine surgery, perfrom a laminectomy in the lower lumbar spine that is kept free of fusion. perform fusion of spine around this laminectomy outcomes for improved wheelchair sitting may lead to temporary loss of upper extremity function Combined PSF with anterior releases/fusion indications curves >100 degrees very young child with high risk of crankshaft phenomenon contraindications pulmonary compromise typically not necessary due to the high flexibility of SMA curves Hip, knee, and ankle contractures Overview Common in the hip and knee Nonambulators also develop ankle equinus Treatment Physical therapy Surgical release is controversial as function in nonwalkers is rarely improved and recurrence is common Prognosis Severity of disease based on number of functional copies of SMN-II Type 1 SMA has the worst prognosis, with majority of patients dying by age 2
QUESTIONS 1 of 13 1 2 3 4 5 6 7 8 9 10 11 12 13 Previous Next (SBQ13PE.106) Survival motor neuron protein deficiency leads to: QID: 5331 Type & Select Correct Answer 1 Progressive replacement of muscle tissue with fibrous and fatty tissue, causing calf pseudohypertrophy 12% (379/3142) 2 Loss of anterior horn cells and progressive muscle weakness 78% (2441/3142) 3 Abnormal chondroid production by chondroblasts in the proliferative zone of the physis 1% (37/3142) 4 Disturbances in cell metabolism with accumulation of sphingolipids in the liver, spleen and bone marrow 3% (106/3142) 5 Fetal acetylcholine receptor inhibition and nonprogressive joint contractures 5% (158/3142) L 2 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2 Review Tested Concept Review Full Topic (SBQ13PE.63) Which of the following is INCORRECT regarding scoliosis in the setting of spinal muscular atrophy (SMA)? QID: 5159 Type & Select Correct Answer 1 Curve flexibility tends to be higher than for idiopathic curves 30% (728/2418) 2 Most curves tend to be long, C-shaped thoracolumbar curves 13% (323/2418) 3 The primary surgical goal for correction is to obtain fusion in a position that will maintain sitting balance and prevent decline of pulmonary function 11% (272/2418) 4 Curve magnitude correlates strongly with ambulatory status 13% (325/2418) 5 Anterior release/fusion with posterior fusion are typically required for adequate surgical correction 31% (754/2418) L 5 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 5 Review Tested Concept Review Full Topic Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (OBQ13.104) A newborn infant is born with the physical exam finding shown in the video below. In addition, the child has absent deep tendon reflexes and hypotonia. Which of the following abnormalities is most likely responsible for these findings? QID: 4739 FIGURES: V Type & Select Correct Answer 1 Gene mutation in SMN1 61% (2788/4536) 2 Deficiency of Dystrophin protein 13% (580/4536) 3 Beta-galactosidase deficiency 16% (710/4536) 4 Gene mutation in COMP 5% (235/4536) 5 Gene mutation in COL1A1 4% (177/4536) L 3 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 1 Review Tested Concept Review Full Topic (SBQ13PE.2) A 12-month-old male presents with symmetric, progressive weakness that is more profound in lower extremity than upper extremity. On physical exam, he can sit but cannot walk. He has tongue fasciculations and absent deep tendon reflexes. Serum creatine phosphokinase and aldolase levels are normal. Which of the following genetic mutations or deletions is responsible for his condition? QID: 4915 Type & Select Correct Answer 1 Dystrophin gene 27% (1521/5600) 2 PMP22 gene 6% (322/5600) 3 Androgen receptor gene 1% (76/5600) 4 SMN-1 gene 55% (3100/5600) 5 Frataxin gene 10% (540/5600) L 4 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 4 Review Tested Concept Review Full Topic Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (OBQ12.233) A 3-month-old infant presents to your clinic with difficulty moving his extremities. The child had an uneventful prenatal course and birth, but since birth he has had poor head control and difficulty feeding. On physical exam, he is able to move all extremities, but he moves his upper extremities more than his lower extremities, and his hands more than his shoulders. He has no spasticity, but global weakness. The patientās deep tendon reflexes are absent, but he has tongue fasciculations. What is the cellular pathology and prognosis for this patient? QID: 4593 Type & Select Correct Answer 1 The patient has a nonprogressive injury to his brain, and he will likely require multiple orthopaedic surgeries in the future as a result of muscle imbalance 8% (273/3263) 2 The patient has an absent dystrophin protein and will likely require a wheelchair by the age of 15 and will die of cardiorespiratory problems by the age of 20 16% (525/3263) 3 The child will have a progressive loss of alpha-motor neurons in anterior horn of spinal cord. He will have difficulty walking, but will be able to sit independently and will likely live into the fifth decade of life 16% (514/3263) 4 The child will have a progressive loss of alpha-motor neurons in anterior horn of spinal cord and will unlikely live past the age of two 58% (1882/3263) 5 The child will likely go on to develop a cavus foot and hammer toes, but he should live a full healthy life 1% (34/3263) L 4 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 4 Review Tested Concept Review Full Topic Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK This is an AAOS Self Assessment Exam (SAE) question. Orthobullets was not involved in the editorial process and does not have the ability to alter the question. If you prefer to hide SAE questions, simply turn them off in your Learning Goals. (SAE07PE.40) A 7-year-old girl with spinal muscular atrophy (SMA) type II has popping of the left hip. Examination reveals painless subluxation of the joint in adduction with palpable reduction in abduction. Radiographs show coxa valga, subluxation of the left hip, and pelvic obliquity with elevation of the left hemipelvis. Treatment should consist of QID: 6100 Type & Select Correct Answer 1 observation. 37% (223/607) 2 bilateral adductor and iliopsoas releases, with nighttime abduction bracing. 9% (57/607) 3 proximal femoral varus osteotomy with internal fixation. 12% (74/607) 4 proximal femoral varus osteotomy with volume-reducing periacetabular osteotomy. 19% (118/607) 5 proximal femoral varus osteotomy with shelf acetabular augmentation. 21% (128/607) N/A Question Complexity E Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 1 Review Tested Concept Review Full Topic (SBQ04PE.40) An autosomal recessive disorder caused by a homozoygous deletion in the survival motor neuron 1 (SMN1) gene would result in which of the following? QID: 2225 Type & Select Correct Answer 1 Global hypotonia, difficulty swallowing, absent deep tendon reflexes, and tongue atrophy, with disease onset within the first 6 months of birth. 44% (902/2040) 2 Delayed motor milestones, scoliosis, and joint contracture, with disease onset around 6-18 months of age 14% (286/2040) 3 Scoliosis, hand tremors, increased lumbar lordosis, and bilateral Trendelenburg lurch, with disease onset later in life (>18 months of age). 6% (131/2040) 4 Any of the above 30% (602/2040) 5 None of the above 4% (83/2040) L 5 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 4 Review Tested Concept Review Full Topic Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK
All Videos (3) Podcasts (1) 13th International Congress on Early Onset Scoliosis - 2019 Effect of SMA Associated Spine Deformity on Respiratory Function in the Era of Genetic Therapy - Brian D. Snyder, MD PhD (ICEOS 2019) Pediatrics - Spinal Muscular Atrophy C 2/10/2020 705 views 3.0 (1) Login to View Community Videos Login to View Community Videos 12th International Congress on Early Onset Scoliosis - 2018 Paper #31 Are Magnetically Controlled Growing Rods a Good Option for Collapsing Spine Deformity in Spinal Muscular Atrophy Type ā 2 Associated Early Onset Scoliosis? - Senol Bekmez, MD (ICEOS 2018, # 90) Senol Bekmez Pediatrics - Spinal Muscular Atrophy D 2/10/2019 41 views 3.0 (1) Login to View Community Videos Login to View Community Videos 12th International Congress on Early Onset Scoliosis - 2018 Paper #30 Pulmonary Function Relative to Stature: Effect of Scoliosis and Treatment in SMA - Brian Snyder, MD (ICEOS 2018, #89) Pediatrics - Spinal Muscular Atrophy D 2/10/2019 49 views 3.0 (1) PediatricsāSpinal Muscular Atrophy Pediatrics - Spinal Muscular Atrophy Listen Now 14:59 min 10/21/2019 258 plays 5.0 (4)