“Technology has advanced more in the last thirty years than in the previous two thousand. The
exponential increase in advancement will only continue,” said Niels Bohr, the Danish physicist
(1885–1962). This sentiment has never been truer than in the understanding of muscular dys-
trophies. From an initial descriptive period in the nineteenth century, to subsequent attempts at
nosography of the disease, we arrived in the genetic era in 1987 when the gene for Duchenne
muscular dystrophy was cloned and its protein product, dystrophin, identifed by Hoffman,
Kunkel, and colleagues. The rest, as they say, is indeed history. The classifcation of muscular
dystrophies is now based on their genetic identity, and ongoing identifcation of the underlying
abnormality associated with each genetic defect has provided a deeper understanding of not
only the mechanisms underpinning abnormal muscle structure and function in these disorders,
but also of normal muscle structure and function. The Holy Grail is an effective cure, and the
last two decades have seen the beginnings of this glorious achievement.
In this book, we have attempted to provide a twenty-frst century update on these disorders.
The phenotypic approach to clinical diagnosis remains the basis of diagnosis, but the avail-
ability of next-generation sequencing techniques has revolutionized the diagnostic algorithm
of the disease. Genetic testing has superseded muscle biopsy in the algorithm. Nevertheless,
Duchenne’s histologic harpoon is not ready to be laid to rest. The muscle biopsy remains rel-
evant to confrm the effect of a genetic variant on myopathological changes and protein expres-
sion in muscle and to identify the pathological fndings associated with novel genes. The
phenotypic and genotypic heterogeneity of many muscular dystrophies is becoming increas-
ingly apparent. Knowledge of the spectrum of extramuscular manifestations, particularly car-
diovascular, informs judicious screening to improve outcomes. Muscle imaging has come of
age as a diagnostic tool and is being investigated as a biomarker. Biomarkers in blood and
tissue are being identifed. Advances in rehabilitation interventions improve the quality of life
at all stages of the disease. Finally, DNA- and RNA-based therapies and gene replacements
have arrived. There is much to do yet, and we hope that this book will serve as a basic reference
in this molecular era of muscular dystrophies.
This book would not have seen the light of day without Dr. Daniel Tarsy’s encouragement.
The authors who have so graciously provided their scientifc, clinical, and literary expertise to
the completion of this book are an absolutely stellar congregation of scientists and clinicians,
and we cannot thank them enough. We extend our appreciation to Swathiga Karthikeyan,
Gregory Sutorius, and Springer Nature Publishing for keeping us on task and making this book
a reality. Finally, our grateful thanks to our families—Padma, Tom, Alamelu, Shruti, and Varun
and to Eriko, Saya, Sota, Nikorn, and Supawadee for their unending support without which
this work would not have been possible.
Boston, MA, USA Pushpa Narayanaswami
Rochester, MN, USA Teerin Liewluck
