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C Longman
Journal Issue: 
Volume 36: Issue 1: 2006




Myotonic dystrophy is the most common form of muscular dystrophy in adults, with a prevalence of 1 in 8,000.  It is a slowly progressive, multi-system disorder  that  affects  skeletal  muscles, the  heart, gastrointestinal  smooth  muscle, uterine smooth muscle, the eyes, and the endocrine and central nervous systems. Myotonic  dystrophy  is  almost  always  caused  by  an  autosomal  dominant  gene mutation in the DMPK gene located on chromosome 19. The gene mutation is an expansion  in  the  length  of  a  three  base-pair  (triplet)  repeat  sequence (cytosine–thymine–guanine, or CTG) above the normal upper limit of 35 repeats. The expanded CTG repeat is classed as a ‘dynamic’ mutation because the number of  repeats  tends  to  increase  in  size  over  successive  generations  in  myotonic dystrophy families.  In general, larger CTG expansions are associated with earlier age-of-onset  and  more  severe  signs  and  symptoms  of  myotonic  dystrophy. Patients with 50–100 CTG repeats may develop cataract, diabetes, grip myotonia, or mild muscle weakness in mid to late adulthood.  Patients with 200–500 CTG repeats  are  affected  earlier  and  more  severely  by  facial  and  distal  limb  muscle weakness  and  myotonia.   A  CTG  repeat  size  above  1,000  is  associated  with prenatal onset of disease and congenital myotonic dystrophy, which may be fatal due  to  respiratory  failure. Feeding  difficulties,  muscle  weakness,  club  foot deformity, and  cognitive  impairments  are  present  in  surviving  infants.  Although males and females are equally likely to inherit myotonic dystrophy, the very large mutations  (>1,000  repeats)  which  result  in  the  congenital  form  of  myotonic dystrophy are virtually always transmitted by an affected mother.  DNA tests are used  to  estimate  repeat  size  and  permit  accurate  prenatal, presymptomatic, and
diagnostic genetic testing.