Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC)

Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is a tumor predisposition syndrome that increases the risk for a triad of features: cutaneous leiomyomas (smooth muscle tumors of the skin), uterine leiomyomas (more commonly referred to as uterine fibroids), and renal cell cancer. An estimated 76% of patients present with single or multiple cutaneous leiomyomas distributed over the trunk and extremities, and more rarely on the face and neck. The skin findings manifest at a mean age of 25 years. Uterine leiomyomas are present in almost all women with HLRCC and occur at a younger age than in the general population. Uterine fibroids are generally large and numerous. Renal tumors occur in ~10-16% of patients with HLRCC, with a median age at detection of 44 years. Most tumors are classified as 'type 2' papillary renal cancer, although tubulo-papillary, tubular, and solid tumor types have been described. The renal tumors are typically unilateral, solitary, and more aggressive than those associated with other hereditary cancer syndromes. The differential diagnosis for HLRCC includes Von Hippel-Lindau (VHL) syndrome and Birt-Hogg-Dubé (BHD) syndrome, both of which are associated with an increased risk for renal cancer. BHD syndrome may present with cutaneous fibrofolliculomas, a skin feature reminiscent of cutaneous leiomyomas in HLRCC. Mutations in the SDHB gene associated with Hereditary Paraganglioma-Pheochromocytoma Syndrome have also been reported in patients with apparently isolated familial renal cell carcinoma.

Tests Available

Forms and Documents

Test Details

FH
  • An individual with a personal history of features associated with autosomal dominant hereditary leiomyomatosis and renal cell cancer (HLRCC, also referred to as Reed syndrome), especially cutaneous leiomyomas (smooth muscle tumors of the skin), symptomatic and/or multiple uterine leiomyomas (fibroids) before age 40 years, and/or tubulo-papillary, collecting-duct, or papillary type II renal cell carcinoma
  • An individual with a personal and/or family history of features associated with autosomal recessive fumarate hydratase deficiency, such as excessive urinary excretion of fumurate, neonatal hypotonia, growth and developmental delay, seizures, structural brain malformations, severe neurologic impairment, dysmorphic facial features, and neonatal polycythemia
  • An unaffected individual with a family history suggestive of HLRCC (see above) when an affected individual is unavailable for his or her own genetic testing
  • Capillary Sequencing
  • Deletion/Duplication Analysis

Ordering

713
3 weeks
2-5 mL Blood - Lavender Top Tube
Buccal Swab | Fibroblasts (separate charge for cell culture may apply) | Oral Rinse

Billing

81405x1, 81479x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Ricketts C et al. J Natl Cancer Inst 2008; 100:1260-126
  2. Wei M-H. et al., Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer. J Med Genet. 2006; 43:18-27
  3. Toro, J.R. et al., Mutations in the Fumarate Hydratase Gene Cause Hereditary Leiomyomatosis and Renal Cell Cancer in Families in North America. Am J Hum Genet. 2003; 73:95-106
  4. Alam, N.A. et al., Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis, renal cancer, and fumarate hydratase deficiency. Hum Mol Genet 2003; 12:1241-1252
  5. Ahvenainen et al. Cancer Genet Cyto 2008; 183:83-88