Screening for MH

There are 2 methods of MH screening; muscle biopsy and genetic testing using DNA samples obtained from venous blood.

For all new families investigation is started by muscle biopsy. As screening, the in-vitro contracture test (IVCT)¹, is performed on living muscle samples the patient has to travel to Leeds for a 1-2 night hospital stay due to travelling problems. The biopsy is usually performed under local regional anaesthesia and is taken from the vastus medialis (part of quadriceps muscle) through a 2-3 inch incision. The results and their implications are discussed with the patient the same day. There is a lower age limit of 10-12yrs mainly due to the size of muscle samples required.

If the clinical diagnosis is confirmed the individual will be screened for a series of mutations in the ryanodine receptor gene (RYR1) that can be used for MH diagnosis following the EMHG protocol² (www.emhg.org).  Should a diagnostic mutation be identified relatives can be offered a preliminary DNA test. If they are shown to carry the familial mutation a positive diagnosis is made and a muscle biopsy is unnecessary. However if undetected a confirmatory muscle biopsy is required before an MH negative diagnosis can be given with assurance. This is for safety reasons in clinical practice, as the genetics of MH is complex and a negative diagnosis needs to be secure. Thus DNA testing alone does not alter the anaesthetic clinical management of patients.

Currently ~40% of UK families are suitable for DNA testing. Current practice screens for certain RYR1 mutations having molecular evidence supporting a pathogenic role in MH (EMHG protocol² www.emhg.org). Testing should be conducted in a molecular genetic laboratory with appropriate accreditation. The MH unit will be able to advise whether or not a patient can be offered a DNA test as they hold the family results. As DNA testing performed in isolation does not alter the anaesthetic clinical management of patients screening requires co-ordination via MH centres who can offer a muscle biopsy if appropriate and also ensure the patient is provided with information about what to do if they require anaesthesia in the future, provide warning cards etc. Collation of family clinical and genetic data is also essential in cases of emergency, the MH unit being the first point of contact by anaesthetists having to treat a suspected case or crisis.

MH Register

All patients who have been investigated are entered onto a register and collated together with family members. All correspondence regarding patients who have previously been referred but not deemed to require screening is also kept. This allows for any queries, such as confirming results or the potential risk of MH in a relative, to be quickly traced.

Contacts
Dr PJ Halsall/Prof PM Hopkins
MH Investigation Unit
Clinical Sciences Building
St James’s University Hospital
Leeds
LS9 7TF

Tel  0113 206 5270
Fax 0113 206 4140

Hotline 07947 609601. This is usually available for medical emergencies only, but it is a mobile phone and therefore sometimes cannot be answered quickly

References

1) The European Malignant Hyperpyrexia Group. A protocol for the investigation of malignant hyperpyrexia (MH) susceptibility. Br J Anaesth. 1984 Nov; 56(11): 1267-1269.

 2) Urwyler A, Deufel T, McCarthy T, West S; European Malignant Hyperthermia Group. Guidelines for molecular genetic detection of susceptibility to malignant hyperthermia. Br J Anaesth 2001 Feb; 86(2): 283-287.