Tuberous sclerosis is a disorder of cellular differentiation with a highly variable clinical expression ranging from a complete lack of clinical manifestations to the classic patient with typical cutaneous lesions and severe neurologic dysfunction. The dominant inheritance pattern of tuberous sclerosis has long been appreciated, although most of the recognized cases are believed to arise from spontaneous mutation. Estimates of the number of familial cases have ranged from 14 to 44% depending on the completeness of evaluation of the proband's family. Genetic counseling of the parents of the child with tuberous sclerosis is difficult, since there is no infallible method of diagnosis of the asymptomatic patient. The presence of periventricular calcifications on computed cranial tomography (CCT) confirms the diagnosis of tuberous sclerosis in some individuals without other findings. Nevertheless, it is still believed that more than half of cases develop by spontaneous mutation. We have previously demonstrated that patients with a well established diagnosis of tuberous sclerosis have high-signal cortical lesions of the cerebral cortex on spin-echo magnetic resonance imaging (MRI). While these cortical MRI lesions tend to be more numerous in severely affected individuals, the usefulness of MRI in identifying asymptomatic carriers of the disease has not been studied. This proposal is intended to evaluate MRI in the identification of mildly affected individuals with tuberous sclerosis. Sixty couples having at least one child with definite tuberous sclerosis will undergo careful physical examination and be studied with cranial MRI. A group of 60 cranial MRI scans done earlier on normal volunteers will serve as controls. The percentage of familial tuberous sclerosis cases identified by MRI will be computed and contrasted with the percentage in earlier published studies. By studying with MRI the parents of 60 children with tuberous sclerosis, we will test our hypothesis that the actual percentage of cases to develop from spontaneous mutation may be lower that current estimates and that MRI may be useful in the detection of brain lesions which might serve as a marker for tuberous sclerosis in the asymptomatic patient.
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| Roach, E S; Kerr, J; Mendelsohn, D et al. (1991) Diagnosis of symptomatic and asymptomatic gene carriers of tuberous sclerosis by CCT and MRI. Ann N Y Acad Sci 615:112-22 |
| Roach, E S; Kerr, J; Mendelsohn, D et al. (1991) Detection of tuberous sclerosis in parents by magnetic resonance imaging. Neurology 41:262-5 |
