A rare subclinical or mild type of Becker muscular dystrophy caused by a single exon 48 deletion of the dystrophin gene

Janusz G Zimowski,Magdalena Pawelec,Joanna K Purzycka,Karolina Ziora-Jakutowicz,Jolanta Kubalska,Jacek Pilch,Magdalena Dudzińska,Jacek Zaremba

doi:10.1007/s13353-017-0391-8

Janusz G Zimowski, Magdalena Pawelec + Show 6 more

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https://doi.org/10.1007/s13353-017-0391-8

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Abstract

In the material of 227 families with Becker muscular dystrophy (BMD), we found nine non-consanguineous families with 17 male individuals carrying a rare mutation—a single exon 48 deletion of the dystrophin gene—who were affected with a very mild or subclinical form of BMD. They were usually detected thanks to accidental findings of elevated serum creatine phosphokinase (sCPK). A thorough clinical analysis of the carriers, both children (12) and adults (5), revealed in some of them muscle hypotonia (10/17) and/or very mild muscle weakness (9/17), as well as decreased tendon reflexes (6/17). Adults, apart from very mild muscle weakness and calf hypertrophy in some, had no significant abnormalities on neurological assessments and had good exercise tolerance. Parents of the children carriers of the exon 48 deletion are usually unaware of their children being affected, and possibly at risk of developing life-threatening cardiomyopathy. The same concerns the adult male carriers. Therefore, the authors postulate undertaking preventive measures such as cascade screening of the relatives of the probands. Newborn screening programmes of Duchenne muscular dystrophy (DMD)/BMD based on sCPK marked increase may be considered.

Highlights

Duchenne/Becker muscular dystrophy (DMD/BMD) is a progressive and irreversible muscle disease
In the material of 227 families with Becker muscular dystrophy (BMD), we found nine non-consanguineous families with 17 male individuals carrying a rare mutation— a single exon 48 deletion of the dystrophin gene—who were affected with a very mild or subclinical form of BMD
The possibility of asymptomatic deletions in the dystrophin gene was first postulated by Koenig et al, who suggested that such deletions can involve exons 31–44, without affecting the reading frame (Koenig et al 1989)

Summary

Introduction

Duchenne/Becker muscular dystrophy (DMD/BMD) is a progressive and irreversible muscle disease. It occurs in two types: the acute type, DMD, with an incidence of 1 in 3500– 5000 live male births, and the milder type, BMD, which is five times less common (Emery 1991; Mendell and Lloyd-Puryear 2013; Moat et al 2013; Romitti et al 2015). In many BMD patients, mobility is preserved for a long time. Sometimes, they start families, and their survival is often comparable to that in the general population (Emery 1991). Therapy of DMD based on exon skipping recently introduced is in development (Cirak et al 2011)

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