Myotonic Dystrophy

  My 5-month old daughter was diagnosed with myotonic dystrophy using chorionic villi sampling at 11 wks in utero.  The DNA test showed her to have a "lower" number of repeats (280 repeats).  My husband is an asymptomatic carrier with 78 repeats.  He is 38 years old.  His father is also an asymptomatic carrier with 65 repeats.  His father is 70 years old.  My husband's sister is 35 years old and has 500 repeats.  Her symptoms are only the myotonia in the hands.  My husband's brother is 30 years old and has 1100 repeats.  His symptoms are much worse.  He has problems with his hands and feet.  In addition, he has muscle weakness in his legs.  When our daughter was originally diagnosed with only 280 repeats, based on family history, we were relieved because from what we had read (which is a lot), the symtoms (symptoms) and age of onset correlate with the number of repeats.  Therefore, her age of onset would be less than that of my husband's sister (500 repeats/age of onset 30 yrs old) and her severity would be no worse (myotonia in her hands although of course that may change over time).  I have recently read in several articles that recent research indicates that the number of repeats in the blood increases throughout the patient's "lifetime" and "adult life" (both terms are used).  My question, therefore, is does this mean that even though she currently has far fewer repeats than my husband's sister (500) and a lot fewer than my husband's brother (1100), that she could ultimately end up with greater numbers of repeats than they have?  In other words, when a fetus is tested, do the number of repeats double, triple, quadruple during the lifetime and/or adult lifetime?  Thank you for your help.

[CCF Neuro[P] MD RPS]

_

Dear Toni:
Sorry to hear about your daughter.  You know the disease well, as you accurately describe anticipation where increased number of triple repeats worsens the phenotypic expression of the disease between generations.  I have heard at meetings the talk about what happens to a person during their lifetime but I have not been convinced that it truely occurs in muscle.  The problem from a theoretical point of view is that muscle is a post-mitotic tissue and the DNA present is not dividing and therefore the number of repeats would not change.  There may be other influences that we are unaware of, but these factors have not been elucidated.  Since, rbc's have no DNA, this should not be an issue in blood.  I would watch as the literature progresses with this disease and triple repeat diseases in general and see about the confounding factors.  I hope for the best with your
daughter.
Sincerely,
CCF Neuro[P] MD