• Genetics

A 47-year-old woman had first presented in her late twenties with complex partial seizures and became seizure-free on carbamazepine. She re-presented 13 years later with migrainous headaches. MR scan of the  brain showed several unusual, non-specific high signal intensity, lesions in the deep and subcortical white matter of both cerebral hemispheres (figure 1). The lesions were typical of subcortical tubers and, as such, a diagnosis of tuberous sclerosis (TS) was queried, although she had no other (peripheral) stigmata of TS.1

TS is an autosomal dominant, multisystem disorder, presenting with multiple harmatomous growths.1 It is usually caused by a mutation in either TSC1 or TSC2, coding for the proteins, hamartin and tuberin respectively.2 Although up to 90% of patients with TS experience seizures, epilepsy is not considered a diagnostic feature. There is no single pathognomonic clinical sign for this condition.3 Given the wide phenotypic variability in TS, Roach et al4 developed a set of diagnostic criteria in 1998 (see box 1 adapted from Hake1). They suggest several major and minor clinical features, but the cardinal signs for suspecting TS are the skin manifestations—in particular, periungual fibromas, adenoma sebaceum, Shagreen patches and ash-leaf macules (which may only be visualised after examination under Wood's light). Despite careful examination of the skin in our patient, there were no peripheral stigmata of TS. There were no dental enamel pits or gingival fibromas. We did not request additional investigations for the presence of rectal polyps and bone cysts. On further questioning the patient disclosed that she was adopted at birth (with no subsequent contact with …