MULTIPLE CUTANEOUS LEIOMYOMAS
This is an autosomal dominant condition in which many small smooth muscle Tumours develop in the skin. These Tumours appear as single or multiple small, firm, painful dermal nodules, fixed to the skin, especially noted on the limbs, trunk, and face, and develop more often in the third decade of life, although they can occur in childhood. Uterine myomas may be associated; 54 % of affected females in one family described in the literature had uterine myomas. These may rarely develop into leiomyosarcomas (Berendes et al. 1971), and there is also an increased risk of type II papillary renal cancer or renal cancer with collecting duct morphology. Affected individuals have reduced fumarate hydratase (FH) activity in lymphoblastoid cells. In the majority of cases, the condition is due to germline heterozygous mutations in the FH gene, a component of the tricarboxylic acid cycle (Martinez-Mir et al. 2003; Tomlinson et al. 2002). Homozygotes (or compound heterozygotes for FH mutations) cause the fumarase metabolic deficiency syndrome characterized by developmental delay and death in the first decade (Tomlinson et al. 2002; Alam et al. 2003). However, not all mutation carrier parents of children with FH deficiency have a predisposition to leiomyomata.
Screening affected individuals should include regular abdominal imaging for renal abnormalities (MRI scans are preferred as tumours can be isoechogenic) (Garman et al. 2003; Wei et al. 2006) which should be initiated early, because cases of renal cancer have been described in individuals as young as 11y with germline FH mutations (Alrashdi et al. 2010).