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Von Hippel Lindau disease is a rare condition characterised by retinal and central nervous system haemangioblastomas. It is also associated with renal cell carcinoma, phaeochromocytoma, and renal, pancreatic, and epididymal cysts.
The disease usually presents with neurological symptoms and/or visual disturbance; angiomas if seen in the retina can often be treated in an attempt to prevent progression to retinal detachment.
We report a young girl with von Hippel Lindau disease whose initial presentation was with a total exudative retinal detachment.
A 14 year old girl presented to the eye casualty department with no perception of light in her left eye. She gave a 2 month history of gradual, painless loss of vision, but had delayed previously mentioning her symptoms.
Past ocular history was unremarkable; an optometrist visit a year previously was normal. She was otherwise well.
Slit lamp examination on the left revealed a quiet anterior segment, with retinal folds visible abutting the posterior lens capsule (Fig 1A). The right eye was entirely normal. An ultrasound B-scan showed a left total funnel retinal detachment (Fig 1B). Computed tomograph scan demonstrated normal orbits.
The patient's identical twin was also present and was examined: both her eyes were normal.
At this stage the family history proved helpful. The patient's father had recently been diagnosed with renal cell carcinoma and pituitary vascular tumours.
The paternal line had a cluster of various carcinomas, including three relatives with cerebellar tumours. Further investigation revealed at least one of these to be histologically confirmed haemangioblastoma. The possibility of von Hippel Lindau disease was raised and the patient's father was screened: the diagnosis was confirmed with polymerase chain reaction analysis; showing a frame shift mutation (single base pair deletion [G]) in codon 195 (exon 3) of the von Hippel Lindau gene. Subsequent extended family screening has revealed the same mutation in the patient and nine other living relatives (Fig 2), including the patient's identical twin. Five of these relatives have clinical manifestations of the disease, and in one case an asymptomatic stage 1 renal cell carcinoma was diagnosed and successfully resected.
Miss AB's left eye has subsequently developed pupil block glaucoma which is currently well controlled medically. It remains blind with a rigid total retinal detachment. The cause of this detachment is most likely to be an optic nerve or retinal haemangioblastoma; however, no causal lesion was identified on ultrasound or computed tomography (CT). The few retinal vessels that can be seen (Fig 1A) do not show any abnormality. Her other eye remains normal and screening for signs of the disease elsewhere has proved negative.
This case highlights the importance of considering von Hippel Lindau disease as a diagnosis when confronted with a patient with an unexplained exudative retinal detachment.
Von Hippel Lindau disease has an autosomal dominant inheritance pattern with an incidence of one in 36 000; with a 70% prevalence of ocular haemangioblastomas. Von Hippel Lindau gene mutation carriers have a 35% probability of visual loss by age 50.1
Ocular angiomas occur commonly in the superotemporal mid-peripheral retina, less commonly on the optic disc (8%), and at the posterior pole (1%).1
If left untreated, lesions can cause vitreous haemorrhage, macular oedema, epiretinal membrane formation, and exudative or tractional retinal detachment. This last complication is well demonstrated in our patient's case, with a 2 month delay between onset of symptoms and first presentation.
Treatment comprises laser photocoagulation of angiomas less than one disc diameter.2 Cryotherapy, or vitreoretinal surgery with trans-scleral drainage and endolaser may be indicated in larger lesions,3 especially if vitreous traction is present.2 Early treatment necessarily offers a better prognosis.
This case underscores the value of taking a good family history in order to detect hereditary diseases, which can then be confirmed with genetic molecular analysis. The importance of identification and subsequent screening of von Hippel Lindau gene mutation carriers (both affected and unaffected) is exemplified in our patient's family—with the potential benefit of early diagnosis and treatment of asymptomatic retinal and cerebellar haemangioblastomas, as well as potentially fatal tumours. The screening should be maintained regularly, as the protean manifestations of von Hippel Lindau disease may occur de novo at any age.3