Duchenne Muscular Dystrophy Diagnosis

Duchenne Muscular Dystrophy Diagnosis Letter

With recent events I have read this letter regarding my Duchenne Muscular Dystrophy Diagnosis again, at the time I received it I was more worried about my fight to get a wheelchair from wheelchair services so left chasing this up with one of my former PAs, she may or may not have actually done as I asked, so this year I will check up on it myself, if nothing else my scientific mind would like more answers.  I was also hesitant at publishing it here due to various reasons including causing someone more pain, but should that happen I will do my best to help.

Daniel Baker at 3 holding a toy gun around the time of Duchenne Muscular Dystrophy Diagnosis
27 April 2012
Dear Daniel,

Re: Yourself Daniel Baker D.O.B. 18.10.1974 Guy’s Hospital ref: xxxxx Diagnosis: Duchenne muscular dystrophy (made in 1977 at Guy’s or East Sussex Hospitals by Dr Robinson, Consultant Neurologist)

Genetic test results: No mutation identified on deletion/duplication screening of all 79 exons, nor on sequencing for point mutation in dystrophin gene (copy of result enclosed).

I am sorry for the delay in confirming for you in writing the outcome of your DNA testing of the dystrophin gene to try to find the mutation underlying your muscular dystrophy. This letter is therefore to follow the email of 3 February 2012 from Jo Affleck in which she let you know that the laboratory at Guy’s Hospital has not been able to find a mutation on full sequencing of the gene, nor previously on looking for evidence of deletion or duplication of exons of the gene. This situation is encountered in less than 2% (less than I in 50) boys/men with Duchenne muscular dystrophy (DMD), although perhaps in up to 7% of those with Becker muscular dystrophy (BMD). However, your own history with diagnosis at age 2 years and requirement for a wheelchair from I I years is of course typical for Duchenne MD.

I understand that the issues prompting you to request mutation analysis are primarily two-fold:

Information on prognosis which had been requested in relation to the most appropriate adaptations or upgrading required of your wheelchair, although there is a strong argument for proposing that this should be whatever is required at present unless the thought was to provide additional functions of the chair in anticipation of the future.

Your own desire to know whether your mutation might be one appropriate for treatment trials in DMD.

In response to the first point, we would argue that you should be entitled to whatever you need most at the present time in order to have maximum mobility and independence which could be made possible through the appropriate electrical devices etc on a chair. Now at age 37 years the best guide to prognosis would be determined by your history over the last 10 years or so, but also by assessment of cardiac and respiratory function, which certainly should be being monitored, and including CPAP ventilatory support at night if required, and if not already in place.

For the second point, in terms of treatment trials, at present it is anticipated that the boys for these would be those with specific mutations involving deletion or duplication of certain exons of the gene; or for different proposed treatment trials, boys with mutations involving a STOP codon. However, we also do not know whether the treatment trials would be offered initially to children at an earlier stage in the course of the condition, where there may be more residual muscle to benefit from any success of the treatment trial.

The third possible reason for wishing to know the specific mutation would be if there were genetic risks
which might depend on this. However, from previous genetic analysis in the family, and particularly from tracking linked markers of the dystrophin gene, we know that the only familial risk is likely to be that your mother could be a carrier, although this was never established. We did not completely eliminate risk for being a carrier for your mother’s two sisters, but it looked as though any risk would depend on one of your grandparents being a mosaic for the mutation and (in your grandmothers case) not passing it to any of your four maternal uncles. The wider family risks were therefore felt to be very
low.

Your DNA result does however also raise the question of the original certainty with which your diagnosis of the Duchenne type of muscular dystrophy, was made. I shall with this letter ask a colleague in the genetics department at Guy’s Hospital if they could possibly find the report on your original muscle biopsy, and perhaps original clinical descriptions from when you were 2 years of age. The biopsy would have predated the discovery of the dystrophin gene, and therefore the specific
immunological staining of a biopsy which could now be done. On the current dystrophin gene sequencing report, the lab at Guy’s indicates that in order to try to detect the mutation in the remaining 2% of DMD cases (or 7% of BMD cases) it would require a muscle biopsy for extraction of the messenger RNA (mRNA) in order to use this as the starting point for trying to find a mutation.

Therefore, for both these reasons if you feel that you would wish to try to define the mutation in your own case, it would require a muscle biopsy in order to pursue this further. This would be used to check the dystrophin immuno staining pattern (as well as several other muscle proteins), but also for extraction of mRNA for the further mutation analysis. If you feel that you would wish to pursue this route, it would depend on your ability to come to Frenchay Hospital, probably for a 1-2 night stay, but prior to that we would I think ask that you be referred to the neuromuscular clinic of Dr Andria Merrison at Frenchay in order that we could fully evaluate your clinical presentation and current clinical needs.

I would suggest therefore that you discuss this with your own doctor if you would wish to pursue this, and would ask then for a referral to be made to Dr Andria Merrison at Frenchay Hospital, Department of Neurology. If however you are already under the care of a neurologist in Cheltenham or Gloucester, please let me know as I would wish to discuss this issue with them first.

Lastly, I am enclosing a copy of your DNA sequencing report.

Yours sincerely,

Dr Peter Lunt MA.MSc.FRCP(UK)
Consultant Clinical Geneticist

 

More information on Duchenne Muscular Dystrophy can be found at MDUK and Action Duchenne.

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