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Factor XII deficiency is associated with thrombosis.1–3 Severe deficiency increases an individual’s prothrombotic tendency but with a mild reduction in levels there is less certainty.4 We present a case of recurrent sixth cranial nerve palsy due to severe factor XII deficiency. To our knowledge, this is the first reported case of a recurrent cranial nerve palsy associated with factor XII deficiency.
A 58 year old white male presented with an acquired constant incomitant horizontal diplopia. He had had a previous episode of horizontal diplopia of 3 weeks’ duration 6 months previously with spontaneous resolution and a further similar episode 18 years before that but had been otherwise well. He was not hypertensive or diabetic, of normal weight and a non-smoker, and without any cardiovascular disease. There was no family or personal history of venous or arterial thrombosis. On examination he was found to have bilateral sixth nerve palsies without any associated headache or papilloedema. Detailed magnetic resonance imaging with contrast and lumbar puncture opening pressure and investigation was normal.
Owing to the recurrent nature of the nerve palsy and the initial young age of presentation, a further prothrombotic examination was undertaken. Laboratory investigations showed a normal full blood count, plasma viscosity, liver function tests, glucose, homocysteine, prothrombin time, and fibrinogen assay. There was a significantly prolonged activated partial thromboplastin time of 74.7 seconds (normal range 24–32), which was still abnormal on repeat testing (90 seconds). Further laboratory studies demonstrated severe factor XII deficiency which was consistent on repeated testing (<1% of normal levels) but otherwise normal levels of protein S, protein C, antiphospholipid antibodies, factor VIII, von Willebrand factor, and the factor V Leiden mutation or prothrombin G20210A allele were not found.
He was fitted with Fresnel prisms to relieve his diplopia and was followed up 3 weeks later. By that time his diplopia had completely resolved and he had full abduction in both eyes.
With this recurrent and resolving pattern of cranial nerve palsy in a patient with no other risk factors for arteriosclerosis and a normal magnetic resonance image and lumbar puncture, the most likely predisposing factor in this case is his prothrombotic state associated with severe factor XII deficiency.
Severe factor XII deficiency is a genetic determinant for thrombosis.2,3 It is not associated with any other clinical manifestations and prolonged activated thromboplastin time is a consistent finding in any level of factor XII deficiency. The only previously reported ophthalmic complications of factor XII deficiency are two cases of central retinal vein occlusion in patients without any vasculopathic risk factors.5 Assay for factor XII is not routinely done on thrombophilia screening protocols. It has been suggested that the frequency of factor XII deficiency (1.5–3%)6 is high enough to warrant the inclusion of factor XII assays in routine thrombophilia screening.7 Detailed thrombophilia screening of healthy populations may produce an identifiable abnormality in 10% but clearly 10% of the population are not clinically affected in their lifetime. Therefore the need for additional management should be assessed according to the presence of concurrent risk factors in an algorithmic fashion.8 Since his cranial nerve palsy resolved quickly and there was no family history of vascular thrombosis he was treated empirically with aspirin, although there is no evidence to support its benefit in this condition.