Michele A Gatheridge1, Jennifer M Kwon2, Jerry M Mendell3, Günter Scheuerbrandt4, Stuart J Moat5, François Eyskens6, Cheryl Rockman-Greenberg7, Anthi Drousiotou8, Robert C Griggs1. 1. Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, New York. 2. Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, New York2Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York. 3. Department of Pediatric Neurology, Nationwide Children's Hospital and Ohio State University, Columbus, Ohio. 4. private practice in Breitnau, Germany. 5. Wales Newborn Screening Laboratory, Department of Medical Biochemistry and Immunology, University Hospital of Wales and School of Medicine, Cardiff University, Cardiff, Wales. 6. PCMA (Provincial Centre for Metabolic Disorders)-Newborn Screening and Genetic Biochemistry Laboratory, University Hospital of Antwerp, Antwerp, Belgium. 7. Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada8Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada. 8. Department of Biochemical Genetics, Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
Abstract
IMPORTANCE: Duchenne muscular dystrophy (DMD) is a candidate for the recommended universal screening panel based on evidence that early corticosteroid treatment improves outcomes and on new genetic therapies that require early diagnosis for effectiveness. Elevated creatine kinase levels in the neonatal period are the initial screening marker in DMD newborn screening programs but is found in inherited muscle disorders other than DMD. Data are needed to inform protocols for future screening and follow-up testing and care in these patients. OBJECTIVES: To review non-DMD muscle disorders identified by prior DMD screening programs and to investigate whether these programs failed to identify patients later diagnosed as having DMD (false-negative findings). EVIDENCE REVIEW: Since 1975, 10 DMD newborn screening programs have provided opportunities to study screening protocols, outcomes, and parental responses. These programs used elevated creatine kinase levels in dried blood spots for the initial screening, with the diagnosis of DMD based on findings of clinical follow-up, muscle biopsy, or direct mutational testing of the DMD gene. Literature regarding these prior programs was reviewed in PubMed, and the programs were discussed directly with the directors when possible to identify diagnoses of non-DMD disorders and false negative results from 1975 to July 12, 2015. Data were collected from screening programs, which were active between 1975 and December 2011. Data were analyzed from March 26, 2015, to August 24, 2015. FINDINGS: The 10 screening programs screened more than 1.8 million newborns between 1975 and 2011, and 344 were diagnosed with DMD. Of those screened, the majority were boys. Across all programs, 80 patients had positive results for non-DMD disorders, including Becker muscular dystrophy and forms of limb-girdle and congenital muscular dystrophies, and 21 patients had false-negative findings for DMD. CONCLUSIONS AND RELEVANCE: Screening for DMD will result in identification of other muscle diseases. Future screening protocols should include infants of both sexes and include follow-up testing algorithms to evaluate patients who do not have DMD gene mutations but may have another muscle disorder associated with elevated neonatal creatine kinase levels. These programs will need to be aware that false-negative results are a possibility.
IMPORTANCE: Duchenne muscular dystrophy (DMD) is a candidate for the recommended universal screening panel based on evidence that early corticosteroid treatment improves outcomes and on new genetic therapies that require early diagnosis for effectiveness. Elevated creatine kinase levels in the neonatal period are the initial screening marker in DMD newborn screening programs but is found in inherited muscle disorders other than DMD. Data are needed to inform protocols for future screening and follow-up testing and care in these patients. OBJECTIVES: To review non-DMDmuscle disorders identified by prior DMD screening programs and to investigate whether these programs failed to identify patients later diagnosed as having DMD (false-negative findings). EVIDENCE REVIEW: Since 1975, 10 DMD newborn screening programs have provided opportunities to study screening protocols, outcomes, and parental responses. These programs used elevated creatine kinase levels in dried blood spots for the initial screening, with the diagnosis of DMD based on findings of clinical follow-up, muscle biopsy, or direct mutational testing of the DMD gene. Literature regarding these prior programs was reviewed in PubMed, and the programs were discussed directly with the directors when possible to identify diagnoses of non-DMD disorders and false negative results from 1975 to July 12, 2015. Data were collected from screening programs, which were active between 1975 and December 2011. Data were analyzed from March 26, 2015, to August 24, 2015. FINDINGS: The 10 screening programs screened more than 1.8 million newborns between 1975 and 2011, and 344 were diagnosed with DMD. Of those screened, the majority were boys. Across all programs, 80 patients had positive results for non-DMD disorders, including Becker muscular dystrophy and forms of limb-girdle and congenital muscular dystrophies, and 21 patients had false-negative findings for DMD. CONCLUSIONS AND RELEVANCE: Screening for DMD will result in identification of other muscle diseases. Future screening protocols should include infants of both sexes and include follow-up testing algorithms to evaluate patients who do not have DMD gene mutations but may have another muscle disorder associated with elevated neonatal creatine kinase levels. These programs will need to be aware that false-negative results are a possibility.
Authors: Jennifer M Kwon; Hoda Z Abdel-Hamid; Samiah A Al-Zaidy; Jerry R Mendell; Annie Kennedy; Kathi Kinnett; Valerie A Cwik; Natalie Street; Julie Bolen; John W Day; Anne M Connolly Journal: Muscle Nerve Date: 2016-06-13 Impact factor: 3.217
Authors: Qing Ke; Zheng-Yan Zhao; Robert Griggs; Veronica Wiley; Anne Connolly; Jennifer Kwon; Ming Qi; Daniel Sheehan; Emma Ciafaloni; R Rodney Howell; Petra Furu; Peter Sazani; Arvind Narayana; Michele Gatheridge Journal: World J Pediatr Date: 2017-05-17 Impact factor: 2.764
Authors: Qing Ke; Li Zhang; Chaying He; Zhengyan Zhao; Ming Qi; Robert C Griggs; Michele A Gatheridge Journal: Neurology Date: 2016-08-23 Impact factor: 9.910