Monday, December 21, 2015

Newborn screening for Duchenne dystrophy

Routine screening of newborns for Duchenne muscular dystrophy (DMD) is under consideration in the United States and elsewhere in the world because of recent developments in diagnostics and treatments.

Some of the implications of such screening are discussed in a review paper published recently in JAMA Neurology.

Senior author, Robert C. Griggs, MD, University of Rochester School of Medicine and Dentistry, New York, explained to Medscape Medical News that it is now realized that identifying patients with DMD at a very early age will be advantageous because corticosteroid therapy can be started before muscle fibrosis has developed and symptoms have clinically manifested.

"Other new treatments, including genetic therapies, are also becoming available, and we believe early treatment will be beneficial," he added.

He said the field is following in the footsteps of cystic fibrosis. Early identification of patients with this disease has led to improved care, which, in turn, has tripled the lifespan of those affected. "We hope similar strides can be made with Duchenne."

Although DMD affects mainly boys because it is an X-linked recessive condition, Dr Griggs recommends that both male and female babies be screened. He points out that it is actually logistically easier to screen all newborns rather than limit testing to boys only.
In addition, some girls can develop DMD — for example, those with Turner's syndrome, who only have one X chromosome, and others with endocrine issues and who are actually genetically male — and by screening girls, carriers of DMD will also be identified...

"This highlights the importance of identification of alternative diagnoses with elevated neonatal CK levels and providing guidance to physicians who follow up these patients," the authors write.
Such conditions include congenital muscular dystrophy and the more commonly Identified limb girdle muscular dystrophies, α-sarcoglycanopathy and dysferlinopathy.

"Many of these other conditions may well be the subject of new treatments in development, too. The whole field is moving forward now," Dr Griggs said.

The authors note that although the sensitivity of initial CK screening for DMD is high, there will also be a possibility of some false-negative results.
They note that false-negative results are an issue because an elevated CK level is a marker that is secondary to the disease process and not a specific indicator of DMD.

Screening newborn CK levels is likely to miss some female DMD carriers, cases of Becker muscular dystrophy, and patients with X-linked cardiomyopathy, they state.

Gatheridge MA, Kwon JM, Mendell JM, Scheuerbrandt G, Moat SJ, Eyskens F,
Rockman-Greenberg C, Drousiotou A, Griggs RC. Identifying Non-Duchenne Muscular
Dystrophy-Positive and False Negative Results in Prior Duchenne Muscular
Dystrophy Newborn Screening Programs: A Review. JAMA Neurol. 2015 Nov 23:1-7.



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.


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.


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.

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