A sporadic case of von Hippel-Lindau disease with a secondary maculopathy as the presenting sign

A 36-year-old male presented with a drop in visual acuity in his left eye to 0.1. Ophthalmoscopy of the affected eye revealed dense, macular, lipid exudates at the posterior pole (Fig. 1) and a single peripheral capillary retinal haemangioma with only moderately enlarged draining vessels (Fig. 2). Retinal findings in the right eye were unremarkable. As the patient had reported headache, magnetic resonance tomography (MRT) of the brain was performed. This showed a single infratentorial haemangioblastoma (Fig. 3) with a solid (arrow) and cystic (arrow) component, thus allowing for a clinical diagnosis of von Hippel-Lindau disease (VHL) (Neumann 1987). However, the subject's family history was negative for this autosomal-dominant, multi-tumour syndrome. Molecular genetic analysis of the VHL gene (3p25–26) by sscp (Latif et al. 1993) detected a mutation (477 C/G) in the patient's DNA (Fig. 4, lane 2), but not in his mother's or sister's DNA (Fig. 4, lanes 3 and 4; wild-type DNA: lane 1). Although a positive family history is present in the majority of VHL cases, the disease can also present sporadically due to a de novo mutation (Richards et al. 1995; Kreusel et al. 2000). Ruthenium-106 brachytherapy of the haemangioma (Kreusel et al. 1998) induced complete regression to a choroido-retinal scar (Fig. 5). During 5 years of follow-up according to current screening recommendations (Maher et al. 1990), no further haemangioma or other new VHL lesions were detected in the patient.

Figure 1. Fundus photograph of the posterior pole of the left eye. Abundant lipid exudates are present, resembling pronounced stellate retinopathy. There is only discrete enlargement of the inferior temporal artery and vein.

Figure 2. In the temporal inferior periphery a capillary retinal hemangioma surrounded by retinal hemorrhage is present. The feeder vessels are only moderately enlarged.

Figure 3. Magnetic resonance image of the patients brain showing an infratentorial hemangioblastoma with a solid (arrow) and cystic (arrow) component. The lesion was removed surgically.

Figure 4. Single-strand polymorphism (SSCP) analysis of exon 1 of the VHL gene after amplification by polymerase chain reaction (PCR) and labelling. The patients blot (lane 2) showed an additional band (arrow) not present in the wild type DNA (lane 1) or the blot of his mother (lane 3) or sister (lane 4). Sequencing revealed an exchange of cytosine for guanine at nucleotide 477.

Figure 5. Fundus view after ruthenium-106-brachytherapy. The hemangioma shows complete regression.