Population-Wide Duchenne Muscular Dystrophy Carrier Detection by CK and Molecular Testing.

Carrier screening of Duchenne muscular dystrophy (DMD) has not been widely evaluated. To identify definite DMD female carriers prior to or in early pregnancy, we studied a large population of reproductive age females and provided informed reproductive options to DMD carriers. 37268 females were recruited from the Hangzhou Family Planning Publicity and Technology Guidance Station/Hangzhou Health Service Center for Children and Women, Hangzhou, China, between October 10, 2017, and December 16, 2018. CK activity was measured with follow-up serum DMD genetic testing in subjects with hyperCKemia, defined as CK > 200 U/L. The calculated upper reference limit (97.5th percentile) of serum creatine kinase (CK) for females aged 20-50 years in this study was near the reference limit recommended by the manufacturer (200 U/L), above which was defined as hyperCKemia. 427 females (1.2%) harbored initially elevated CK, among which 281 females (response rate of 65.8%) accepted CK retesting. DMD genetic testing was conducted on 62 subjects with sustained serum CK > 200 U/L and 16 females with a family history of DMD. Finally, 6 subjects were confirmed to be DMD definite carriers. The estimated DMD female carrier rate in this study was 1 : 4088 (adjusting for response rate), an underestimated rate, since only 50% to 70% of DMD female carriers manifest elevated serum CK, and carriers in this study may have been missed due to lack of follow-up or inability to detect all DMD pathogenic variants by current genetic testing.

Splinting in Carpal Tunnel Syndrome: The Optimal Duration.

INTRODUCTION: The purpose of this study was to evaluate optimal neutral wrist splint duration in treatment-naive mild and mild to moderate carpal tunnel syndrome (CTS). Neutral wrist splinting is a conservative treatment for CTS; however, no clear guidelines exist for how long splinting should be prescribed for optimal outcomes. MATERIALS AND METHODS: In this prospective clinical trial subjects were assigned to wear a neutral wrist splint for 6 (group A) or 12 weeks (group B). Symptom and functional outcomes were assessed by questionnaire at baseline, 6 and 12 weeks. Median nerve sensory and motor latencies were recorded at baseline and 12 weeks. Pretreatment, midtreatment, and posttreatment measures were compared within and between treatment groups where applicable. This study was approved by the United States Air Force Academy institutional review board. RESULTS: A total of 30 subjects (37 hands) were randomized to 2 treatment groups. Mean symptom severity and median sensory peak latency significantly improved in both groups at 12 weeks, without a significant difference between groups. Mean functional severity significantly improved only in group A. CONCLUSION: Neutral wrist splint for 6 weeks resulted in better clinical improvements in patients with untreated mild and mild to moderate CTS. There was no additional benefit in extending splinting 6 additional weeks. This is the first study to compare duration of wrist splint use beyond 8 weeks. A larger sample size is needed to identify the reason for lack of functional improvement in group B. Long-term follow-up of this cohort will be helpful to determine the natural history of initial wrist splint use.

Progress in treatment and newborn screening for Duchenne muscular dystrophy and spinal muscular atrophy.

BACKGROUND: Advances in treatment for Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) hold promise for children with these disorders. Accurate genetic diagnosis, early in the disease process, will allow these treatments to be most effective. Newborn screening (NBS) for SMA has been recommended in the United States, and a pilot DMD NBS program is underway in Hangzhou, China. DATA SOURCES: A PubMed search, limited to the past 5 years, was conducted to identify: (1) therapeutic advancements for DMD/SMA approved by the United States Food and Drug Administration or the European Medicine Agency and (2) The status of NBS for DMD/SMA. RESULTS: We review the current state of approved treatments for DMD/SMA. We present recommendations regarding the future of NBS for these diseases, with a focus on the outcomes and challenges of SMA NBS in New York, USA, and the DMD NBS pilot program in Hangzhou, China. CONCLUSIONS: Approved treatments for DMD and SMA may change the natural history of these diseases. Long-term studies of these treatments are underway. To avoid the known diagnostic delay associated with these disorders and provide optimal effectiveness of these treatments, early identification of patients through NBS will be necessary. Establishing comprehensive follow-up plans for positively identified patients will need to be in place for NBS programs to be successful.

Identifying Non-Duchenne Muscular Dystrophy-Positive and False Negative Results in Prior Duchenne Muscular Dystrophy Newborn Screening Programs: A Review.

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.