Peri-operative considerations for a pregnant patient with Werner syndrome and pre-eclampsia

Abstract

Werner syndrome was first described by Otto Werner in 1904 [1]. It is a rare autosomal recessive syndrome caused by a mutation of the RecQ type DNA/RNA helicase on the WRN gene resulting in accelerated ageing [1, 2]. Due to infertility and gonadal failure, the majority of female patients with Werner syndrome do not become pregnant. If pregnancy does occur, it can pose challenges for the anaesthetist.  Typical features include premature greying and hair loss, loss of subcutaneous adipose tissue, muscle wasting of the limbs, central adiposity, a ‘bird-like’ face, short stature and a classic high pitched voice. Age-related systemic disorders include type 2 diabetes mellitus, osteoporosis, atherosclerosis, cataracts, thyroid disease, vocal cord paralysis and malignancy. A full list of features is shown in Table 1. Severe forms of arteriosclerosis and atherosclerosis are common in all patients with Werner syndrome. Myocardial infarction is the leading cause of death, followed by malignancy. Over 50% of patients with Werner syndrome present with myocardial infarction, angina pectoris, stroke or hypertension before the age of 40 [2]. Case reports describe on-table cardiac arrest secondary to aortic stenosis and severe calcification of coronary vessels during a caesarean birth in a patient with Werner syndrome, and a caesarean birth performed for exacerbation of coronary symptoms and signs of cardiac insufficiency [3, 4]. Mortality usually occurs in the fourth or fifth decade and the physiological age of a patient with Werner syndrome may be greater than their chronological age. Therefore, consideration should be given to the choice and dose of medications administered. A difficult airway should be anticipated due to the craniofacial abnormalities which affect 98% of patients with Werner syndrome including small mouth, mandibular and maxillary hypoplasia. Difficult intravenous access should also be anticipated due to scleroderma-like skin changes which affect 96% of patients with Werner syndrome [5]. Anaesthetic techniques for pregnant patients with Werner syndrome should be decided on a case-by-case basis with thorough pre-operative investigations and multidisciplinary team discussion.

A 34-year-old gravida 2, para 0 woman with Werner syndrome was reviewed at the anaesthetic pre-operative assessment clinic at 24-week gestation as part of her antenatal care with the high-risk medical team. She had been diagnosed with Werner syndrome in her 20s, having initially presented with non-alcoholic hepatic steatosis. Genetic studies had confirmed homozygosity for the pathogenic variant c3961C>T (p.Arg1321Ter) in the WRN gene. She had a number of typical features of Werner syndrome (Table 1). Of particular note was her history of dysphonia, a glottic gap, right vocal cord paralysis and partial left vocal cord paralysis. Her regular medications were levothyroxine 75 μg and labetalol 100 mg daily for hypothyroidism and essential hypertension, respectively. New onset exertional dyspnoea developed at 24-week gestation, which was investigated with transthoracic echocardiography. This showed an ejection fraction of 55% (compared to 65% 5 years previously). Systolic and diastolic ventricular function were normal. Mild sclerosis of the aortic valve without regurgitation or stenosis was reported. A sigmoid septum was observed, which was new. This is a benign feature of ageing that would be unusual for someone in their 30s. Previous microlaryngoscopy revealed her significant dysphonia was due to a glottic gap, right vocal cord paralysis and partial left vocal cord paralysis. The otolaryngology team had listed the patient for a staged injection thyroplasty but delayed this elective procedure until after the pregnancy. A glucose tolerance test at 28-week gestation was strongly positive, and insulin therapy was commenced. At 30-week gestation, the patient was admitted to her local hospital following an episode of hypoglycaemia and was noted to be hypertensive without proteinuria. She was admitted to our hospital for closer monitoring where her insulin doses were reduced. Serial growth scans and fetal monitoring were reassuring.

Neuraxial anaesthesia was deemed safe due to adequate cardiac function on echocardiogram. We also wanted to avoid general anaesthesia and intubation because of potential airway complications. At 34-week gestation, while still an inpatient, the decision was made to proceed with caesarean birth due to derangement of liver function tests and rising blood pressure, initially treated with labetalol 200 mg twice and 10 mg of nifedipine orally. A category 2 caesarean birth was performed uneventfully in daytime hours under spinal anaesthesia. Postoperatively the patient was admitted to the high-dependency unit for monitoring. She remained stable and returned to her baseline labetalol therapy. She was discharged to ward level care 2 days later and the rest of her postoperative period was uneventful.

Patient's perspective: ‘I am very grateful for the care that I received during my pregnancy. I was so excited because having a baby was something I dreamed of for so long. On the morning of my section I had a headache which was a bit scary. Everyone was around the bed to look after me and I knew me and my baby were in good hands. I remember worrying that my partner wouldn't get in on time but luckily he did. I know I went to theatre but a lot of my memory after that is blurry. Mostly, I just remember feeling very very sleepy. I am very happy everything went ok. Sometimes I get very tired during the day but for me it's worth it’.