Recessive Gene Myopathies Clinical Trial
Official title:
Clinical Importance of Carrier Status of Recessive Gene Mutations in Myopathy
Many myopathies are inherited in a recessive manner, but in some of these recessively
inherited disorders, clinical manifestations may potentially manifest in carriers of just a
single mutation.
The aim of the study is to describe the clinical characteristics of single mutation carriers
of recessive myopathy, through measuring serum creatine kinase, muscle strength, muscle
degeneration (by MRI) and heart affection. The investigators will do this by blood sampling,
Biodex 4 Isokinetic Dynamometer, MRI analysis, ECG, Holter monitoring, and echocardiography.
The aim is further to describe whether these characteristics are found primarily with
specific mutations.
Background:
Many myopathies are inherited in a recessive manner, but in some of these recessively
inherited disorders, clinical manifestations may potentially manifest in carriers of just a
single mutation. This has recently been demonstrated by researchers for the recessively
inherited limb girdle muscle dystrophy (LGMD) type 2A, where carriers of single mutations can
also be symptomatic. In X-linked recessively inherited dystrophinopathies caused by mutations
in the DMD gene on chromosome Xp21, female mutation carriers may also manifest with disease,
although this is often milder than affected men. In the recently discovered LGMD2L,
manifesting carriers are also suspected. Thus, according to statistics, too many persons
evaluated for myopathy carry a single LGMD2L mutation.
Some previous studies have looked into the significance of being a single mutation carrier in
recessive muscle disease. In dystrophinopathy, it was reported that 5 % of female DMD
carriers reported myalgia and cramps, 17 % experienced mild-to-moderate muscle weakness and 8
% experienced dilated cardiomyopathy, with a mean onset age of approximately 30 years.
Another study found that echocardiographic examination was abnormal in up to 38% of DMD
female carriers - some with dilated cardiomyopathy, and some with left ventricle dilatation.
Overall, however significance of carrying a single mutation of recessive myopathy is widely
unexplored. No study has yet investigated the characteristics of single mutation carriers of
recessive myopathy in an observational, cross-sectional study.
Aim:
In this study, clinical characteristics of single mutation carriers of recessive myopathies
will be investigated. The investigation will include sceletal muscle degeneration and
strength, as well as cardiac status.
Recruitment and Methods:
Estimated total of subjects recruited is 200 with known recessive gene mutations, and 40
healthy controls. In former studies 40 healthy volunteers have already been investigated,
thereby giving a total of 80 healthy controls. Recessive gene carrier recruits will be
obtained via the Department of Clinical Genetics and Copenhagen Neuromuscular Center,
Rigshospitalet, thus only including carriers aware of their carrier status.
2 days of testing per participant. Day one: Measuring S-creatine kinase level (blood
sampling), muscle strength (Biodex 4 Isokinetic Dynamometer), ECG, and Holter monitor device
application.
Day two: Holter monitor device removal, Dixon MRI analysis with gadolinium contrast medium,
and echocardiography.
Healthy controls will take part in MRI-scanning and isokinetic dynamometer testing.
Trials are expected to be carried out between October 2016 and May 2020.
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