Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Hereditary leiomyomatosis and renal cell cancer

This disease is characterized by multiple cutaneous and uterine leiomyomata. The inheritance is autosomal dominant with incomplete penetrance.

Epidemiology

It is a rare disease, so it is generally accepted that uterus leiomyomatomas and kidney tumors are not sufficient to make the clinical diagnosis, if skin leiomyomas are not present.<br>In contrary, in 6% of patients with a mutation, a kidney tumor can be found in family members by radiological methods.

Test Strategy

In any patient with malignant tumors and skin leiomyomas a molecular genetic test is recommended. If a mutation is found, a family screening will follow, and finally, all affected family members shall perpetually a scrutinely examined for tumors.

Clinical Findings

The most obvious clinical symptome are cutaneous leiomyomas. Uterine leiomyomata and even sarkomata may occur in women. Malignant tumors associated with this disease may be found in prostata and breats.

Diagnosis

The leading symptome are multiple cutaneous leiomyomas. Only if such a dermatologically confirmed presentation is associated with tumors a molecular genetic test is indicated.<br>Heterozygous patient should be screened for kidney tumors by radiological methods. A thorough clinician keeps an eye on other possible tumors, too.

Pathogenesis

The disease is caused by mutations of the FH gene (fumarate hydratase). Relevant mutations can be found in 85% of patients. Amon them 58% missens, 27% frameshift, 9% nonsense, and 7% mutation affecting large parts of the gene.

Systematic

Hereditary renal tumors
Hereditary leiomyomatosis and renal cell cancer
COL4A6
FH
Hereditary papillary renal cell carcinoma
Nonpapillary renal cell carcinoma
Wilms tumor
von Hippel-Lindau syndrome

References:

1.

Alam NA et al. (2005) Fumarate hydratase mutations and predisposition to cutaneous leiomyomas, uterine leiomyomas and renal cancer.

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2.

Orphanet article

Orphanet ID 523 [^]
3.

OMIM.ORG article

Omim 150800 [^]
4.

Wikipedia article

Wikipedia EN (Hereditary_leiomyomatosis_and_renal_cell_cancer_syndrome) [^]
Update: April 29, 2019