FLORENCE, ITALY — Multiple skin leiomyomas may be the first sign of multiple cutaneous and uterine leiomyomatosis, a hereditary disease that can include highly symptomatic uterine fibroids and, in a small percentage of cases, aggressive renal cancer, N. Afrina Alam, M.B., reported at the 13th Congress of the European Academy of Dermatology and Venereology.
Dr. Alam has been working with a multidisciplinary team studying this disease, once thought rare. Just 20 cases had been reported worldwide a few years ago when she began studying multiple cutaneous and uterine leiomyomatosis (MCUL), said Dr. Alam, formerly of the Centre for Cutaneous Research at St. Bartholomew's Hospital and the London.
Cutaneous leiomyomas appear in patients in their teens or 20s, and they are “very variable in their severity,” said Dr. Alam, now of St. John's Institute of Dermatology at St. Thomas Hospital in London. She found 50 index cases herself, and in the ensuing years, significantly more cases have been identified in the United Kingdom and elsewhere.
In a study of 108 patients with MCUL, the mean number of skin leiomyomas was 25. Nearly 90% of patients reported at least one painful skin lesion.
Skin lesions tend to predate other manifestations of the disease by 5ndash;10 years, making them critically important in terms of their diagnostic relevance, Dr. Alam said.
If uterine leiomyomas develop as part of the syndrome, they are histologically indistinguishable from other fibroids but tend to be “very severely symptomatic, with a high risk of hysterectomy,” she said. By age 55, more than half of women with the syndrome had undergone hysterectomies.
The UK team identified aggressive renal cancer in 9 of 89 families carrying the multiple leiomyomatosis gene. One study subject died of metastatic renal carcinoma at age 18 years.
Researchers who have studied the MCUL's genetic profile have found that highly penetrant mutations in an enzyme on chromosome 1 cause the condition, an autosomal dominant disease. A host of mutations has been found in affected families, and certain patterns have emerged.
For example, a mutation dubbed G354R FH appears to be associated with uterine fibroids without skin manifestations. Certain truncating mutations, especially frameshift mutations, appear to be linked to development of renal cancer, which was far more common in females than in males in the MCUL study.
Among 26 males carrying any MCUL mutation, all 26 had skin leiomyomas. Among 67 female mutation carriers, 46 had both skin and uterine leiomyomas, 10 had only skin leiomyomas, and 5 had only uterine leiomyomas. Mutations in six patients were nonpenetrant.