We will investigate the clinical manifestations and molecular genetic defects of heritable urologic malignant disorders. Families with urologic malignancy with known or suspected genetic basis will be enrolled. Affected individuals or individuals suspected of having a germline urologic malignant disorder will undergo periodic clinical assessment and genetic analyses for the purpose of: 1) definition and characterization of phenotype, 2) determination of the natural history of the disorder, and 3) genotype/phenotype correlation. Genetic linkage studies may be performed in situations in which the genetic basis of the disorder has not been elucidated.

Population

Patients with known or suspected inherited urologic malignant disorders and their biologic family members with inherited urologic malignancies will be recruited primarily from the urology, oncology, and genetics communities worldwide

Brief Title

Von Hippel-Lindau (VHL): Clinical Manifestations, Diagnosis, Management and Molecular Bases of Inherited Renal and Other Urologic Malignant Disorders

Official Title

Von Hippel-Lindau (VHL): Clinical Manifestations, Diagnosis, Management and Molecular Bases of Inherited Renal and Other Urologic Malignant Disorders

Brief Summary

We will investigate the clinical manifestations and molecular genetic defects of heritable <br /> urologic malignant disorders. Families with urologic malignancy with known or suspected <br /> genetic basis will be enrolled. Affected individuals or individuals suspected of having a <br /> germline urologic malignant disorder will undergo periodic clinical assessment and genetic <br /> analyses for the purpose of: 1) definition and characterization of phenotype, 2) <br /> determination of the natural history of the disorder, and 3) genotype/phenotype correlation. <br /> Genetic linkage studies may be performed in situations in which the genetic basis of the <br /> disorder has not been elucidated.

Detailed Description

Background:

- Disorders under investigation are: Autosomal dominant inherited urologic malignant
disorders including: von Hippel-Lindau (VHL), hereditary papillary renal cancer (HPRC),
Birt Hogg Dube (BHD) and hereditary leiomyomatosis and renal cell acarcinoma (HLRCC) as
well as familial renal cancer.

- Studies have led to the identification and characterization of the VHL, HPRC, FLCN and
HLRCC genes.

- The genetic etiology of the most common type of inherited kidney cancer, familial renal
cancer (FRC), remains to be determined.

Objectives:

- To characterize the natural and clinical histories of inherited urologic malignant
disorders.

- To determine the genetic etiology of hereditary urologic malignant disorders in which
the gene variation is unknown, by linkage analysis, positional cloning and evaluation of
candidate genes.

- To correlate specific mutations and their associated protein domains with disease
phenotypic expression based on parameters including presenting age, clinical
manifestations, histopathology and rate of recurrence.

- To identify and describe as yet unknown or uncharacterized inherited urologic malignant
disorders.

Eligibility:

- Individuals and biologic family members with a suspected or an established diagnosis of
an inherited urologic malignancy in which the disease gene is known, including von
Hippel-Lindau (VHL) and hereditary papillary renal carcinoma (HPRC).

- Individuals and biologic family members with a suspected or an established diagnosis of
an inherited urologic malignancy in which the disease gene is not yet known,
specifically hereditary forms of Type II papillary renal cancer, clear cell renal
carcinoma, renal oncocytoma, chromophobe renal carcinoma or Birt Hogg Dube.

- Individuals and biologic family members who have urologic malignant diseases of
suspected, but not proven genetic etiology, including families with more than one
individual affected by the same or related cancers.

Design:

- These rare families will be recruited to genetically confirm diagnosis, determine size
and location of renal tumors, size at presentation, growth rate and metastatic potential
of renal tumors.

- Genetic testing will be offered to gain appreciation of the effect of mutations on the
relative activity of various germline and somatic mutations.

- We will determine if there is a relationship between mutation and disease manifestations
and phenotype.

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.