Retinal angiomatosis and von Hippel-Lindau disease.
BACKGROUND
To evaluate the significance of angioma number (single or multiple) for the presence of von Hippel-Lindau (VHL) disease in patients presenting with capillary retinal angioma.


METHODS
Forty-one nonrelated patients presenting with capillary retinal angioma were evaluated. An ophthalmic workup, screening for other organ lesions, and molecular genetic screening for a mutation of the VHL gene was performed. The diagnosis of VHL was made on the basis of the personal and family history, the presence of other VHL-associated organ lesions, or the presence of a mutation of the VHL gene.


RESULTS
Thirteen patients (32%) presented with a single angioma and 28 patients (68%) presented with multiple angiomas. In 81% of all patients, VHL could be diagnosed. Diagnosis of VHL could be readily made by the personal or family history in 51% of all patients. In another 27% of all patients, VHL disease was evidenced by screening for other VHL-associated lesions. In two patients (3%) VHL could be diagnosed by molecular genetics only. All patients with multiple retinal angiomas had VHL disease and, in 38% of patients with a single angioma, VHL was present. Reasons for a missing family history in patients with VHL disease were the presence of a de novo mutation (15% of VHL patients) or clinical anticipation of VHL disease (18% of VHL patients).


CONCLUSIONS
The presence of multiple retinal angiomas strongly suggests VHL disease, which, however, can be obscured by presence of a de novo mutation or by clinical anticipation of VHL disease in affected families. A single retinal angioma may be sporadic as well as the presenting sign of VHL. Diagnosis and screening for this multitumor syndrome is substantially supported by molecular genetics.
Kreusel
K M
KM
Augenklinik, Klinikum Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. KMKreusel@aol.com
Bechrakis
N E
NE
Heinichen
T
T
Neumann
L
L
Neumann
H P
HP
Foerster
M H
MH
D000293:Adolescent; D000328:Adult; D015139:Blotting, Southern; D002648:Child; D004247:DNA / Q000032:analysis; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D016147:Genes, Tumor Suppressor / Q000235:genetics; D018324:Hemangioma, Capillary / Q000150:complications / Q000175:diagnosis*; D006801:Humans; D008025:Ligases; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics; D019572:Retinal Neoplasms / Q000150:complications / Q000175:diagnosis*; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000150:complications / Q000175:diagnosis* / Q000235:genetics
D011506:Proteins; D025521:Tumor Suppressor Proteins; D004247:DNA; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human