A molecular genetic analysis should performed upon suspicion of HLRCC based on the abovementioned criteria for diagnosis and /or the following:
• multiple cutaneous leiomyomata, with at least one histologically positive leiomyom or
• one leiomyoma and an HLRCC-positive family anamnesis, or
• one tumor and a cutaneous leiomyomatosis without a HLRCC-positive family anamnesis, or
• one (or more) "Type 2" papillary, tubular- papillary or collecting duct system renal cell tumors and HLRCC-positive family anamnesis.
Leiomyomatosis, HLRCC - FH
Clinical Features
Hereditary leiomyomatosis with renal cell carcinoma (HLRCC) is an autosomal dominant inheritance characterized by leiomyomas and/or renal cell carcinomas. Approximately 75 % of patients show cutaneous leiomyomas as a leading symptom of HLRCC (multiple or single, 40 %). Leiomyomas appear mostly between the ages of 20 and 30 and increase during the clinical course in both size and number. Almost all affected women also develop numerous large leiomyomas of the uterus. Approximately 15 % of affected patients exhibit renal cell carcinomas (mostly unilateral, solitary and progressively aggressive). According to the literature, uterin sarcoma, prostate carcinomas and breast cancer correlate with HLRCC.
• Cutaneous Leiomyomata:
The majority of HLRCC patients exhibit single or several cutaneous leiomyomas. These most often appear as toned pustules or nodules, localized on the trunk and extremities; they sometimes also occur in the face. 40 % of HLRCC patients show only mild cutaneous symptoms (five or less lesions).
• Uterine Leiomyomata:
Leiomyomas (numerous and large) of the uterus occur in almost all women affected by HLRCC and correlate with cutaneous leiomyomas. In these cases, the average age of diagnosis varies from 18 to 52 years of age.
• Renal Cell Cancer:
Kidney tumors occur in approx. 15 % of HLRCC patients. Most tumors have been classified as Type 2 papillary kidney carcinomas displaying a characteristic papillary histopathology. Besides tubulo-papillary tumors, kidney manifold carcinomas have also been described.
Genetic Information
HLRCC is caused by germ line mutations in the FH gene which is located on chromosome 1 (1q43), consists of 10 exons, and encodes for the TCA cycle enzyme Fumarat-Hydratase (Fumarase). Germ line mutations in the FH gene have been detected in nearly all patients with clinical symptoms of HLRCC.
Diagnostic
Indication
Method
All Exons as well as their flanking regions are analyzed using DNA-sequencing.
Deletions and/or duplications of one or more exons in the FH gene are captured using MLPA.
Sample Requirement
2 - 4 ml of EDTA blood
Duration
2 - 3 weeks