Prenatal diagnosis for Duchenne muscular dystrophy (DMD) was introduced in the Netherlands in 1984. We have investigated the impact of 26 years (1984-2009) of prenatal testing. Of the 635 prenatal... Show morePrenatal diagnosis for Duchenne muscular dystrophy (DMD) was introduced in the Netherlands in 1984. We have investigated the impact of 26 years (1984-2009) of prenatal testing. Of the 635 prenatal diagnoses, 51% were males; nearly half (46%) of these were affected or had an increased risk of DMD. As a result 145 male fetuses were aborted and 174 unaffected boys were born. The vast majority (78%) of females, now 16 years or older, who were identified prenatally have not been tested for carrier status. Their average risk of being a carrier is 28%. We compared the incidences of DMD in the periods 1961-1974 and 1993-2002. The incidence of DMD did not decline but the percentage of first affected boys increased from 62 to 88%. We conclude that a high proportion of families with de novo mutations in the DMD gene cannot make use of prenatal diagnosis, partly because the older affected boys are not diagnosed before the age of five. Current policy, widely accepted in the genetic community, dictates that female fetuses are not tested for carrier status. These females remain untested as adults and risk having affected offspring as well as progressive cardiac disease. We see an urgent need for a change in policy to improve the chances of prevention of DMD. The first step would be to introduce neonatal screening of males. The next is to test females for carrier status if requested, prenatally if fetal DNA is available or postnatally even before adulthood. Show less
Helderman-van den Enden, A.T.J.M.; Bergen, J.C. van den; Breuning, M.H.; Verschuuren, J.J.G.M.; Tibben, A.; Bakker, E.; Ginjaar, H.B. 2011
Helderman-van den Enden ATJM, van den Bergen JC, Breuning MH, Verschuuren JJGM, Tibben A, Bakker E, Ginjaar HB. Duchenne/Becker muscular dystrophy in the family: have potential carriers been tested... Show moreHelderman-van den Enden ATJM, van den Bergen JC, Breuning MH, Verschuuren JJGM, Tibben A, Bakker E, Ginjaar HB. Duchenne/Becker muscular dystrophy in the family: have potential carriers been tested at a molecular level? Duchenne muscular dystrophy (DMD) is the most common inherited neuromuscular disease. After identification of the mutation in the index patient, family members can be reliably investigated. Carriers should be informed about their risk of having offspring with the disease and about their own risk for cardiomyopathy for which regular cardiac surveillance is recommended. In a small country like the Netherlands with well-organized genetic services, one would expect that most DMD families are adequately informed about the above mentioned risks for carriers. We have investigated whether women at risk had been tested at a molecular level. In the national Duchenne/Becker database 311 DMD and 99 Becker muscular dystrophy (BMD) patients had been registered up to 1 July 2009. These patients were asked to give information about the number of sisters and maternal aunts of the DMD/BMD patient and anything that was known about their genetic status and that of the mother. This information was compared with the information known at the genetic laboratory. Thirty-five of 104 adult sisters/maternal aunts of DMD patients with a 50% risk of being a carrier and 45 of 148 adult women with a 4.3% risk because of germ line mosaicism for DMD had not been tested by DNA analysis. Our study indicates that about one third of the potential carriers have not been tested. Given the possible far-reaching clinical consequences of being a carrier, further studies are needed to investigate the reasons why potential female carriers have not been tested. Show less
Theoretically, 13% of patients with Duchenne muscular dystrophy may benefit from antisense-mediated slopping of exon 51 to restore the reading frame, which results in the production of a shortened... Show moreTheoretically, 13% of patients with Duchenne muscular dystrophy may benefit from antisense-mediated slopping of exon 51 to restore the reading frame, which results in the production of a shortened dystrophin protein. We give a detailed description with longitudinal follow up of three patients with Becker muscular dystrophy with in-frame deletions in the DMD gene encompassing exon 51. Their internally deleted, but essentially functional, dystrophins are identical to those that are expected as end products in DMD patients treated with the exon 51 skipping therapy. The mild phenotype encourages further development of exon 51 skipping therapy. (C) 2010 Elsevier B.V. All rights reserved. Show less
