Leiomyomatosis hereditary with leiomyomas of the uterus D48.9

Autosomal dominant clinical picture (Choudhary S et al. 2013) characterised by cutaneous, mostly multiple, disseminated or also grouped, less frequently striped, 0.2 - 1.0 cm large, skin-coloured to brownish, often pressure painful nodules. As in HLRCC (Hereditary leiomyomatosis and renal cell carcinoma), the hereditary leiomyomatosis with renal cell carcinoma, leiomyomas of the uterus occur in almost all affected women. Further casuistically described are associations with an ovarian cystadenoma (Hüller C et al. 2011), with a leiomyoma of the stomach and with colonic polyps (Serra D et al. 2012).

Hereditary leiomyomatosis with leiomyomas of the uterus is based, as in HLRCC, on germline mutations of the FH gene (fumarate hydratase gene). The FH gene is located on chromosome 1 (1q42.3-43), consists of 10 exons and codes for the enzyme of the citric acid cycle of fumarate hydratase. Of the 155 mutations detected, 58% are missense mutations, 27% are frame shifts, and 9% are nonsense mutations. A correlation between the genotype of the FH mutation and the phenotype could not be determined so far.

The mutations lead to an accumulation of fumarate; this leads to an increase of fumarate via various pathways. This leads to an increase in HIF (hypoxia-induced factor) via various mechanisms. The elevated HIF level in turn induces the transcription of growth factors such as VEGF (vascular endothelial growth factor) and GLUT-1 (glucose transporter type 1), a condition which in the present genetic disposition leads to the corresponding tumor proliferation.

First occurrence between the ages of 20 and 30; in a larger study (n= 108) the time of the initial examination was 24 years. Progression in size and number in the further course.

1. Alam NA et al (2005) Clinical features of multiple cutaneous and uterine leiomyomatosis: an underdiagnosed tumor syndrome. Arch Dermatol 141:199-206.
2. Collgros H et al (2015) Multiple cutaneous and uterine leiomyomatosis or reed-syndrome: a retrospective study of 13 cases. Actas Dermosifiliogr 106:117-125.
3. Choudhary S et al (2013) Multiple cutaneous and uterine leiomyomatosis syndrome: a review. J Clin Aesthet Dermatol 6:16-21.
4. Emer JJ et al (2011) Reed's Syndrome: A Case of Multiple Cutaneousand Uterine Leiomyomas. J Clin Aesthet Dermatol 4:37-42.
5. Hüller C et al (2011) Cutaneous and uterine leiomyomatosis and ovarian cystadenoma associated with deficiency of fumarate hydratase. Dermatol Pract Concept1: 25-27.
6. Serra D et al (2012) Gastric leiomyoma and hyperplastic polyposis coli in a patient with multiple cutaneous and uterine leiomyomatosis. J Cutan Med Surg 16:208-211.