Pregnancy complicated by Werner syndrome

Dear Sir, Werner syndrome, also known as ‘adult progeria’ is a very rare autosomal recessive genetic disorder of accelerated aging with incidence ranging from 1 in 100,000 to 1 in 1,000,000 cases. It is related to a mutation of the WRN gene, which encodes DNA helicase-like protein. A variety of diseases associated with aging, including preterm atherosclerosis with concomitant circulation disorders, venosclerosis, type 2 diabetes, cataract, skin ulcerations (especially at the ankles and tarsal joints) and sclerodermal skin lesions, are characteristic of Werner syndrome. Moreover, the patient's appearance is characteristic: they possess a short stature, small face with large unusually prominent eyes, small jaw, frequently with tooth loss, alopecia, prominent veins, particularly on the scalp, short and broad nails, short and pointed distal phalanges (acroostyleosis), and stiffness of the lower limbs with contractured knees. The initial clinical symptoms of premature aging appear during puberty, when no pubescent acceleration of growth occurs (1). The average life expectancy for patients with Werner's syndrome is around 45 years. Due to underdevelopment of the genital organs, pregnancy in Werner syndrome patients is extremely rare. Even rarer are cases of pregnancy where living, healthy newborns are delivered. A 34-year-old woman in the 32nd week of pregnancy was admitted for observation to the Clinic of Gynecology and Obstetrics. She was diagnosed with Werner syndrome at 19 years and had a history of confirmed bilateral cataracts, osteoporosis, peripheral vascular angiopathy and premature atherosclerosis. At the age of 26 years, she was diagnosed with ischemic heart disease, arterial hypertension and lipid disorders (hyperlipidemia). For about 5 years increasing symptoms of heart failure were observed, along with stenocardial symptoms unrelated to exercise and successfully treated with immediate nitroglycerine. Coronarography performed in 2003 revealed marked (80–95%) stenosis of the left coronary artery and 70–80% stenosis of the right coronary artery. Echocardiographic examination showed normal ventricular contractions, morphology and valvular function, and an ejection fraction of 55–60%. Due to underlying disease, the degree of clinical changes and deep ulcerations of the left lower limb, the patient was disqualified from cardiosurgical treatment. The progressing heart failure was initially treated with statins, metazidine, diuretics, angiotensin-converting enzyme inhibitors and aspirin. During pregnancy, the treatment was switched to calcium channel blockers, aspirin and immediate nitrates. Disorders of carbohydrate metabolism were subjected to dietary treatment and insulin therapy. Amniocentesis along with genetic tests were performed at 15 weeks of gestation and revealed a normal female karyotype. At around the 20th week of gestation, cyanosis was observed around the patient's mouth along with increasing ischemic changes noted on electrocardiography. In spite of severe chest pain, the patient was hemodynamically stable. During hospitalization, aspirin was stopped and low-molecular-weight heparin (enoxaparin) given, whereas insulin therapy, immediate nitroglycerin and antibiotic therapy of ulcerations (piperacillin and tazobactam) were continued. Due to increasing symptoms of heart failure and after a cardiologic consultation, it was decided at 34 weeks that the pregnancy would be terminated by cesarean section. After hydration, the patient had spinal anesthesia with 2.1 ml of 0.5% marcaine injected between L3 and L4. Fifteen minutes after the introduction of anesthesia, arterial blood pressure dropped to 80/60 mmHg from the baseline value of 150/90 mmHg. Effective compensation was achieved with ephedrine and fluid transfusion. During the entire procedure, the patient received oxygen through a facial mask, and the SaO2 was around 98–100%. The patient delivered a 1950 g female baby in good condition. No complications were observed during the procedure and postoperative period. Bromocriptine was added to the therapeutic protocol in order to stop lactation during the postoperative period. The patient was discharged 10 days after surgery. Five months later, both the woman and her infant were doing well. Only three cases concerning pregnancy and confirmed Werner syndrome have been described. In all these cases, birth was preterm (30–34 weeks). Isthmocervical insufficiency was probably the reason for the preterm labor in these cases; however, the authors did not comment on the circulatory system status of the patients (2-4). Life-threatening, persistent acute coronary episodes along with increasing heart failure were the basic problems in our patient. However, no typical cervical insufficiency was observed (5). Langesaeter et al. emphasize that pregnant patients with heart disorders qualify as a high-risk group, but can safely be given spinal anesthesia for an elective cesarean section (6). This point of view is accepted in our clinic and consequently we performed spinal anesthesia in our patient while keeping in mind the necessity of compensating for the drop in arterial blood pressure. This report has been approved by the Local Ethical Committee of the Pomeranian Medical University in Szczecin.