Hereditary Kidney Cancer And Kidney Disease

There are several kinds of hereditary kidney cancer (or renal cell carcinoma or RCC). The most well known may be the Von Hippel Lindau syndrome; other syndromes include Birt-Hogg-Dubé, Hereditary Leiomyomatosis Renal Cell Carcinoma (HLRCC), Chromosome 3 (Translocation), Tuberous Sclerosis, Familial Renal Oncocytoma.

A diagnosis for one of these syndromes is often missed – people are just told they have kidney cancer. Hereditary RCC is rare, perhaps less than 5% of all kidney cancers, so many competent doctors never see a case. They are not incompetent because they do not see a connection right away.

Sometimes the way to diagnose a hereditary syndrome is by linking it to other symptoms you may have, symptoms that may not be on the list that you check off when you give your doctor your health history. Diagnosis many come from linking many symptoms that many family members have. In your family, the symptoms that are manifestations of a hereditary syndrome may show up in people of different ages in different families, so it is hard for your doctor to know that they even exist. How many times has a doctor asked you what symptoms your mother’s sister and mother’s uncle have that could relate to something you and your nephew have?

Also, for unknown reasons, people today do develop hereditary RCC and are diagnosed as the first in the family.

It is important to know if RCC is hereditary because other family members may be affected, and because screening and treatment will be related to the underlying cause. Other issues, such as the ability to get insurance and the potential for genetic discrimination, also play a role. Some families have hereditary RCC and do not recognize it because there is only 1 case of RCC in the family, but there are other family members who have other symptoms of a hereditary syndrome (this can be especially true of families with the Von Hippel Lindau syndrome).

Many pathology types are found in hereditary RCC. Typically, a person with one of the hereditary symptoms will NOT have all of the symptoms for their syndrome. Testing is available for some of the syndromes. The lists of symptoms for the syndromes or types of hereditary RCC are just overviews.

Von Hippel Lindau

Symptoms:

• renal cysts (simple and complex) and renal tumors (often bilateral, multifocal.) VHL kidney cancer is always, only, clear cell. It can metastasize and become aggressive. 28-45% of VHL patients get kidney cancer.
• hemangioblastomas of the central nervous system and eyes (can lead to blindness and paraplegia if untreated)
• endolymphatic sac tumors (tumors of the ear – can lead to hearing loss)
• pancreatic cysts and neoplasms
• pheochromocytomas in many areas of the body
• adrenal tumors

The tricky thing about VHL is making the connection. For example, in a family where one person has benign brain tumors, another kidney cancer, and another benign tumors in the back or ovarian cysts, family members will not always think to connect this. Doctors don’t always put the picture together.

There is a DNA test for VHL – the gene has been identified.

For more information, see:

• Von Hippel Lindau Family Alliance
• Von Hippel-Lindau Syndrome – Gene Review

Chromosome 3 (Translocation)

Symptoms:

• Kidney tumors. This is clear cell kidney cancer, which can be connected to chromosome 3. It is very rare.

May be related in some way to VHL; not much is known about it.

HLRCC (Hereditary Leiomyomatosis Renal Cell Carcinoma)

Symptoms:

• Renal tumors (Type II Papillary). Can be very aggressive, may metastasize quickly – are often just single tumors, not multi-focal.
• Skin conditions – leiomyomata, on back, chest, arms, legs (may resemble a rash of raised red bumps)
• Uterine fibroids (usually ages 20-35) / leiomysarcoma (rare)

The gene has been identified and you can be tested. It is very important to find a knowledgeable kidney cancer expert if you have or suspect you have HLRCC.

For more information, see:

• HLRCC Family Alliance
• HLRCC – Gene Review

Birt-Hogg-Dubé

Symptoms:

• kidney cysts (simple and complex) and tumors (often bilateral, multifocal). The tumors can be oncocytic, hybrid oncocytic, chromophobe, papillary and clear cell. This cancer does not usually metastasize, with some exceptions for some clear cell and papillary. 15-30% of BHD patients will get RCC.
• skin conditions: fibrofolliculomas ( skin bumps on face, upper chest, neck ,earlobes – anywhere from on to several hundreds. Acrochordons ( skin tags) and tri
• spontaneous pneumothoraxes, or lung collapses, associated with
• tiny benign lung cysts/lung blebs that can potentially cause collapsed lungs

The gene for this has been identified; you can be tested.

For more information, see:

• Birt-Hogg-Dubé Family Alliance
• BHD Syndrome website
• Birt-Hogg-Dubé – Gene Review
• Birt-Hogg-Dubé Syndrome

Hereditary Papillary Renal Cell – Type 1

Symptoms:

• papillary kidney cancer – may grow slowly, can metastasize; cysts may be present, but are not common. The cancer may be bilateral and multifocal.

The gene has been identified.

For more information, see:

• Multifocal Renal Cancer, Genetic Basis and Its Medical Relevance Donald P. Bottaro and W. Marston Linehan
• List of articles on Hereditary Papillary Renal Cell
• Hereditary Papillary Renal Carcinoma Type I. Authors: Pathirage G. Dharmawardana; Alessio Giubellino; Donald P. Bottaro
• Hereditary papillary renal cell carcinoma

Familial Renal Oncocytoma

Symptoms:

• benign kidney (renal) tumors, often in both kidneys, often multiple
• kidney performance can be affected
• From scans, it is hard to see if these are malignant or not – don’t take the chance. This syndrome may be connected to BHD.

The gene has not been identified.

For more information, see:

• Familial renal oncocytoma: clinicopathological study of 5 families

Hereditary Nonpolyposis Colon Cancer

Symptoms:

• colon cancer
• sometimes urinary tract tumors, epithelial tumors of renal pelvis
• cancers of endometrium, pancreas, stomach, small bowel, urothelium, ovaries, biliary system
• sometimes related to transitional cell RCC

For more information, see:

• Lessons from the skin – cutaneous features of familial cancer
• What is HPNCC?
• Hereditary Non-polyposis Colorectal Cancer

Tuberous Sclerosis

Symptoms:

• Renal (kidney) tumors. 1-2% of TS patients get RCC, which can basically be all of the types of kidney cancer.
• Angiofibromas /angiomyolipoma
• Retinal hartomas
• Cortical tubers/ cerebral sclerosis
• Giant cell astrocytomas
• Dermatological signs on the face
• Cardiac tumors

The TS gene has been identified; testing is available.

For more information, see:

• Tuberous Sclerosis
• Tuberous Sclerosis Complex – Gene Review
• Tuberous Sclerosis Alliance

LAM- Lymphangioleimyomatosis – is related to TS but is not hereditary; it affects the lungs in women, sometimes the kidney.

For more information, see:

• The LAM Foundation

ADPKD (Autosomal Dominant Polycystic Kidney Disease)

Symptoms:

• Kidney cysts – very rarely kidney tumors
• RCC, or kidney cancer, is rare in ADPKD.

For more information, see:

• PDK Charity
• Differences between ARPKD and ADPKD.htm

Unknown Cause

Symptoms:

• renal cell cancer (pathologies may differ from family to family), more than one family member with RCC, can metastasize.

This is a very frustrating diagnosis. The physical symptoms may even mimic one of the known syndromes, but in some cases the gene test does not show any of the known mutations.

We have been hearing from a few families who outwardly seem to have BHD, but who do not have any of the 50 known mutations.

For more information, see:

• Hereditary Renal Cancers, Peter L. Choyke, MD, Gladys M. Glenn, MD, PhD, McClellan M. Walther MD, Berton Zbar, MD and W. Marston Linehan, MD. Correspondence to P.L.C. (email: pchoyke@nih.gov).
• Cancer Guide