Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05036148 |
| Other study ID # |
KDAR FN Brno MH |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
September 1, 2021 |
| Est. completion date |
December 31, 2021 |
Study information
| Verified date |
April 2022 |
| Source |
Brno University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The Academic centre for Malignant Hyperthermia of Masaryk University (ACMHMU) was established
in 2021 in Brno, Czech Republic and consists of four academic departments of Medical Faculty
of Masaryk University in two tertiary university hospitals, University Hospital Brno and St.
Anne Faculty Hospital. These departments collaborated and operated since 2002 and since 2019
is Brno one of the of centre of EMHG (www.emhg.org). Aim of this study was to describe the
Czech and Slovak (CZ-SK) cohort of MHS patients, the biggest Slavonic MHS cohort known by
now, and to fill the knowledge gap about the Slavonic population in perspective of MH.
Description:
We evaluated every referral to the MH centre since 2002 then. IVCT results, clinical data,
personal and family history and molecular genetic data, have been recorded in an electronic
medical record. Potential MHS patients, probands, were investigated according to the European
Malignant Hyperthermia Group (EMHG) recommendations using IVCT and/or RYR1 and CACNA1S
sequence variant screening. Each proband is a representative of one unrelated family. As the
diagnostic guidelines were changing in the time, so was our diagnostic algorithm with the
development of new knowledge and methods.
Originally before 2015, for each proband or the nearest relative in case that the index case
could not be tested, MH must be confirmed/excluded by IVCT. Only with a positive IVCT
positive result (MHS, MHEh, MHEc), genetic diagnosis was originated.
iIn 2015, a new EMHG guideline for the diagnosis of MH was issued and significantly moved the
DNA diagnosis of MH to the forefront and we started to use genetic testing as a first
diagnostic step. Not finding the diagnostic variant does not exclude MH susceptibility and
IVCT needs to follow for final diagnosis. IVCT has been providing according to the best
practise and EMGH guidelines.
So far, the genetic diagnosis of MH in the Czech Republic has been in several stages -
starting with standard scoring of 33 most common causal diagnostic variants of the RYR1 gene
by using multiplex ligation-dependent probe amplification (MLPA) (SALSA MLPA probemix
P281-A3/P282-A3 RYR1, MRC Holand). In case of a negative result, direct sequence analysis of
the RYR1 and CACNA1S gene sections followed, where the remaining causal diagnostic variants
occur. Since 2021 MLPA and direct sequencing of hot spots regions of RYR1 and CACNA1S was
routinely replaced by next-generation sequencing (NGS) at the level of a panel of genes
associated with neuromuscular diseases (including RYR1, CACNA1S and STAC3).
