Emery–Dreifuss muscular dystrophy (EDMD) is a heterogeneous genetic disorder characterised by early contractures, progressive muscle weakness and cardiomyopathy. Inheritance may be X-linked (EDMD1) or autosomal (EDMD2), both dominant and rarely recessive. Expressivity varies with the underlying gene mutation and delivers a range of clinical presentations and severity. The most common disease pattern begins with contractures of the Achilles tendons, elbows and postcervical muscles. This is followed by humeroperoneal muscle weakness which later involves the proximal limb girdles. Finally, in their second or third decade, patients usually develop cardiac conduction defects: PR interval prolongation and heart block. Occasionally, cardiac abnormalities arise in the absence of other characteristics and are thought to account for some cases of sudden cardiac death.1–3
Anaesthetic considerations include difficult neuraxial and endotracheal access due to contractures. Respiratory muscle weakness, ventricular myopathy and arrhythmias may all exist to varying degrees. Previous case reports have made reference to perceived risks shared with commoner muscular dystrophies (prolonged neuromuscular blockade, delayed gastric emptying and anaesthesia-induced rhabdomyolysis),2,4 although evidence to support these links in EDMD is lacking.5,6 A full range of anaesthetic techniques have reportedly been used safely in this rare patient cohort.4
We would like to share our management of a 28-year-old female with a sporadic lamin A/C gene mutation. The patient has provided written consent to publication of the details. This fit mother of two had met all of her developmental milestones, but had, at the age of 7 years, developed lower limb weakness and Achilles tendon contractures. Initial investigation was hampered by lack of consent for tissue biopsy and a presumed diagnosis of Charcot–Marie–Tooth disease was made. During her late teens and first pregnancy, she experienced palpitations and, at the age of 23 years, development of elbow contractures prompted further investigation and diagnosis of EDMD. At this time, an implantable cardioverter-defibrillator (ICD) was suggested but cardiac risks were not quantifiable; her young age guaranteed multiple ICD box changes and with her slight stature and breast hypoplasia, she had concerns about the box's cosmetic appearance. Having completed her family and with progression of her ECG abnormalities, she opted to combine ICD insertion with bilateral breast augmentation to hide the ICD unit and address her perceived masculine figure.
On examination, this 50-kg lady had obvious wasting of her upper arms and thighs, walked with a waddling gait and had a 30° extension deficit at both elbows. She had virtually no flexion in her cervical spine from neutral, rotation was limited to 40° both left and right, but extension was unaffected. Her airway assessment was unremarkable (Mallampati grade 1). Cardiac investigation revealed first degree atrioventricular block, with inferolateral T wave flattening and inversion; echocardiography was essentially normal. Her history was otherwise unremarkable apart from demonstrating her physiological reserve by having had two children by spontaneous vaginal delivery and having uneventfully undergone two previous, volatile-based general anaesthetics (enflurane) for Achilles tendon transfer procedures.
For this dual procedure, she received a standard anaesthetic induction with fentanyl 75 μg, propofol 180 mg and rocuronium 30 mg. Tracheal intubation was straightforward (grade 1 view using direct laryngoscopy). Anaesthesia was maintained with sevoflurane in oxygen and air. In addition to standard monitoring, we carefully monitored neuromuscular response with a simple nerve stimulator, nasopharyngeal temperature, invasive arterial pressure and depth of anaesthesia with Entropy (Datex-Ohmeda, GE Healthcare, Waukesha, Wisconsin, USA). External defibrillator pads were placed on the posterior aspect of her right shoulder and left axilla prior to commencing surgery. In the operating theatre, a single ICD wire was inserted through the left subclavian vein; its position was confirmed by radiographic screening and impedance check. A subpectoral pocket was then created for left breast augmentation, and the ICD wire was tunnelled to the superior aspect of this pocket and connected to the ICD unit. At this stage, the ICD was tested (two successful terminations of induced ventricular fibrillation) and deactivated until diathermy was complete. The ICD unit was then secured slightly above the breast implant and the breast augmentation process replicated on the right. The electrophysiology team remained on standby throughout, in case rapid ICD reactivation was necessary. Observations were stable throughout the 3-h operation. A spontaneous return of four responses to ‘train-of-four’ stimulation was observed before waking and residual paralysis was reversed with neostigmine 1.25 mg to ensure optimum postoperative respiratory function. Recovery was quick and uneventful and the patient was discharged home on the first postoperative day. Figure 1 shows her postoperative chest radiograph.
This patient displayed EDMD2 due to a de novo mutation in the lamin A/C gene, the prevalence of which is unknown. This gene codes for the alternatively spliced lamin A and C proteins which make up a matrix that provides stability and strength to the nuclear envelope. Lamin A/C gene mutations may also result in the phenotypically similar limb-girdle muscular dystrophy type 1B (LGMD1B) and autosomal-dominant dilated cardiomyopathy with conduction defects (CMD1A). These three are all classified as laminopathies, can suffer the same cardiac abnormalities and may each manifest as the result of one identical inherited mutation.7
Individuals with EDMD who display a cardiac phenotype are at risk of both impaired ventricular function and conduction abnormalities. Normal myocardium is slowly replaced by fibro-adipose tissue, resulting in dilated cardiomyopathy and disruption of cardiac pacemaker cells. Clinically, this results in variable sino-atrial and atrio-ventricular conduction: low amplitude P waves, first degree heart block and eventually a junctional escape rhythm or complete heart block. Atrial standstill is pathognomonic of EDMD.2,8 The risk of sudden cardiac death in these individuals is difficult to quantify because the condition is so rare. A meta-analysis of 299 patients with lamin A/C mutations showed that 92% of those over 30 years of age had dysrhythmias. Mean life expectancy was 46 years, with 12% of deaths attributed to heart failure and 46% of patients suffering sudden cardiac death.9 Unfortunately, quantifying this risk as a cumulative or annual risk which is meaningful to those affected remains difficult.7
Perioperative management of patients with EDMD requires careful preoperative evaluation, with a cardiac focus and cautious anaesthesia tailored to the scenario and guided by level 4 evidence (Table 1).1,2,4–6,10–12 We chose to use a volatile anaesthetic with muscle relaxant based on our patient's age and previous uneventful exposure. Theoretically, these patients may share the risk of rhabdomyolysis and arrhythmogenic electrolyte disturbance associated with the use of volatile agents and succinylcholine in Becker's and Duchenne's muscular dystrophy, and this should be considered particularly in the first decade of life.6,10
This case illustrates that implantation of an ICD as part of a dual procedure is a safe and simple way of facilitating elective surgery which would otherwise carry a significant risk of perioperative arrhythmias. It also provides definitive management of EDMD sufferers’ life-long risk of sudden death in line with emerging evidence.3,7
Assistance with the study: none declared.
Financial support and sponsorship: none declared.
Conflicts of interest: none of the authors reports any conflict of interest.
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