This expansion occurs at the end of the DMPK gene, in the 3 untranslated region. DMPK is located on the long arm of chromosome 19. DMPK codes for myotonic dystrophy protein kinase, a protein expressed predominantly in skeletal muscle.Between 5 and 37 repeats is considered normal; between 38 and 49 repeats is considered pre-mutation, and although not producing symptoms, children can have further repeat expansion and symptomatic disease; greater than 50 repeats almost invariably is symptomatic, with some noted exceptions. Longer repeats are usually associated with earlier onset and more severe disease.DMPK alleles with greater than 37 repeats are unstable and additional trinucleotide repeats may be inserted during cell division in mitosis and meiosis. Consequently, the children of individuals with premutations or mutations inherit DMPK alleles which are longer than their parents and therefore are more likely to be affected or display an earlier onset and greater severity of the condition, a phenomenon known as anticipation. Repeat expansion is generally considered to be a consequence of the incorporation of additional bases as a result of strand slippage during either DNA replication or DNA repair synthesis. Misalignments occurring during homologous recombinational repair, double-strand break repair or during other DNA repair processes likely contribute to trinucleotide repeat expansions in DM1. Paternal transmission of the congenital form is uncommon (13%), possibly due to selection pressures against sperm with expanded repeats, but juvenile or adult-onset is equally transmitted from either parent.
There are two general categories of approaches to mitral valve repair: resection of the prolapsed valvular segment (sometimes referred to as the "Carpentier" approach) and installation of artificial chordae to "anchor" the prolapsed segment to the papillary muscle (sometimes referred to as the "David" approach). With the resection approach, any prolapsing tissue is resected, in effect removing the hole through which the blood is leaking. In the artificial chordae approach, ePTFE (expanded polytetrafluoroethylene, or Gore-Tex) sutures are used to replace the broken or stretched chordae tendonae, bringing the natural tissue back into the physiological position, thus restoring the natural anatomy of the valve. With both techniques, an annuloplasty ring is typically secured to the annulus, or opening of the mitral valve, to provide additional structural support. In some cases, the "double orifice" (or Alfieri) technique for mitral valve repair, the opening of the mitral valve is sewn closed in the middle, leaving the two ends still able to open. This ensures that the mitral valve closes when the left ventricle pumps blood, yet allows the mitral valve to open at the two ends to fill the left ventricle with blood before it pumps. In general, mitral valve surgery requires "open-heart" surgery in which the heart is arrested and the patient is placed on a heart-lung machine (cardiopulmonary bypass).