Diagnosis, Screening and Clinical Care of Individuals with Tuberous Sclerosis Complex

OVERVIEW T uberous sclerosis complex (TSC) is a dominantly inherited, genetic disorder affecting cellular differentiation, proliferation and migration early in development, resulting in the development of tumors in multiple organ systems, often referred to as hamartias and hamartomas. The diagnosis of TSC and evaluation of at-risk persons involves careful examination of the skin, heart, lungs, eyes, brain and kidneys. Presenting features may be in any or all of these organs and the prognosis can be difficult to predict, with variability ranging from a mild disorder manifesting only as skin findings and asymptomatic brain lesions to a more severe course involving epilepsy, intellectual disability, autism spectrum disorder and extensive kidney disease. Accurate diagnosis allows for timely referrals of affected individuals to appropriate specialists to determine if other problems exist. However, many individuals with TSC report that their diagnosis came after much delay or uncertainty. Despite being one of the more common genetic disorders seen in children and adults, with an estimated incidence of one per 5,800 live births, the diagnosis of TSC is often difficult or delayed due to the variable expression of the disease and the variable age of onset of the symptoms. Genetic testing may now aid in the diagnosis of TSC because DNA testing identifies the mutation in either the TSC1 or TSC2 gene in more than 90 percent of the cases. The following review discusses the diagnosis and features of TSC, the importance of coordinating further evaluations for individuals with TSC and their family members and the role that genetic testing will play in TSC diagnosis and management. Note: Terms highlighted with bold type throughout the text are defined in the Glossary. T here are no known pathognomonic signs for TSC as no single clinical feature is unique to the disease. In addition, many features known to be present in some individuals with TSC, such as epilepsy and intellectual disability, are too common in the general population to help establish the diagnosis. A constellation of features is therefore necessary for a diagnosis of TSC, with more specific features contributing more heavily to the diagnosis and an increasing number of features making the clinical suspicion of TSC more likely. convened a consensus conference to evaluate and review the clinical diagnostic criteria that had been previously established in 1992. Recommendations made by the assembled experts were published in the Journal of Child Neurology and provide the most specific clinical …