Retinal angiomas, central nervous system hemangiobla-stoma, bilateral multifocal clear type RCC, pheochromo-cytoma, pancreatic cyst, neuroendocrine tumor, cystadenomas of epididymis and broad ligaments.Endo-lymphatic sac tumors.
Bilateral, multifocal RCC of papillary type I. Typically at sixth decade. Manifestation confined to the kidney.
Aggressive unilateral RCC papillary type 2, early metastasizing with high fatality, leiomyomat-osis of the skin and uterus. No clear genotype-phenotype correlation.
Facial fibrofollicu-lomas, pulmonary cysts, spontaneous pneumothorax and bilateral RCC of different histologies.
Multiple, bilateral RCC.
Hyperparathyroidism fibroosseus tumors of maxilla and mandible and renal manifestations.
Unilateral clear type RCC, no extra renal manifestations described, age of presentation earlier than sporadic cases.
Identified in sporadic cases of clear RCC not known in oncocytomas chromophobe or oncocytomas
Identified in parathyroid carcinoma, not known in relation to renal manifestations.
According to genotype-phenotype correlation VHL is divided into 4 types. Type 1 low chance of developing pheochromo-cytoma, type 2 subdivided into 2A (low RCC risk) 2B (high RCC risk) and 2C associated with pheochromo-cytoma only.
Homozygotes or compound heterozygotes in C-terminal portion of VHL gene associated with autosomal recessive familial erythrocytosis (Chuvash polycythemia)
Trisomy of chromosome 7 on cytogenetic analysis of the tumors indicating duplication of the affected gene.
Homozygotes or compound heterozygotes of FH mutations are associated with autosomal recessive syndrome, FH deficiency (OMIM 606812)
Chromophobe RCC and oncocytomas are the most common types. Clear cell and papillary type are also described.
Kidney involvement is the only feature. No reported systemic manifestations of VHL disease
Renal manifestations include papillary RCC, polycystic renal disease and hamartomas resembling Wilms tumor.