K. Yang1, S. T. Iannaccone2,3, L. S. Burkhalter2, J. S. Reisch4, C. Cai5, D. T. Schindel1,2 1University Of Texas Southwestern Medical Center,Department Of Surgery,Dallas, TX, USA 2Children’s Medical Center,Division Of Pediatric Surgery,Dallas, Tx, USA 3University Of Texas Southwestern Medical Center,Department Of Pediatrics,Dallas, TX, USA 4University Of Texas Southwestern Medical Center,Department Of Clincal Science,Dallas, TX, USA 5University Of Texas Southwestern Medical Center,Department Of Pathology,Dallas, TX, USA
Introduction: Neuromuscular disorders (NMDs, disease of muscle, nerve, and neuromuscular junction) occur 1 in 3500 worldwide. NMD often requires extensive workup that may not yield a specific diagnosis. Traditionally, diagnosis depended on operative biopsy, that often gave non-specific results depending on the lab’s expertise. Recent advances in molecular genetics suggest that less invasive genetic testing should be the initial approach, reserving biopsy for later. Additionally, due to various algorithms for different NMD categories, the decision to do biopsy first can be difficult. Our goals were to demonstrate the diagnostic utility of muscle/nerve biopsy within the pediatric population at an academic center and offer recommendations for genetic testing in relation to biopsy to achieve the highest diagnostic yield.
Methods: Following IRB approval, we reviewed the EMR of 221 pediatric patients who underwent muscle and/or nerve biopsy for NMD at our center from 1/07 to 3/18. Demographics, family history, clinical presentations, genetic testing and pathology results, complications, clinical diagnoses, and follow up data were collected. Genetic testing included any NMD single gene testing or multiple gene panel testing as well as whole exome sequencing. We compared those who received genetic testing prior to biopsy with those who received genetic testing after biopsy to determine the effect on diagnostic yield. Chi square analysis was done for statistical significance.
Results: 220 patients underwent muscle biopsy and 15 patients underwent nerve biopsy. Not all patients received genetic testing. 119 patients had genetic testing prior to biopsy and 68 patients received genetic testing following biopsy. The average age at time of biopsy was 7.7 years (range 1 month to 18 years), 63% male and 73.7% Caucasian. No surgical or anesthesia complications were noted. Biopsy revealed histological abnormalities in 62.9% (139) and were sufficient to make a specific clinical diagnosis in 33.9% (75). When genetic testing was done before biopsy, pathogenic variants were found in 7.6% (9) and the biopsy identified histological abnormalities in 64.7% (77). When genetic testing was done after biopsy, pathogenic variants were found in 39.7% (27) and biopsy identified abnormalities in 75% (51). The distribution of biopsy results was comparable and not influenced by the timing of genetic testing (p-value 0.345). Genetic testing yield for pathogenic variants was higher when done after biopsy (p-value<0.001).
Conclusion:Muscle and nerve biopsies are safe and may provide significant diagnostic value. Biopsy helped to rule in or out NMD and to guide genetic testing. Our data suggest NMD genetic testing yield was higher when done after biopsy.
