Tuberous sclerosis complex

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By Hema R Murali MBBS and Narayana S Murali MD

Tuberous sclerosis complex is of autosomal-dominant inheritance with high penetration; the risk of an affected parent having an affected child is 50%. However, occurrence of tuberous sclerosis complex in a majority is sporadic and, in part, may be because there exists high intrafamilial heterogeneity. Thus, a mildly affected asymptomatic parent is at high risk of having a child with epilepsy and severe mental retardation. The mutation rate for tuberous sclerosis complex is high, and most of the severely affected children have a new mutation. Reduced expression of the gene, non-expression, and somatic and germline mosaicism, make determination of the true rate of mutation difficult. Prenatal detection of tuberous sclerosis complex in an at-risk fetus is possible by echocardiography or ultrasonography, demonstrating cardiac rhabdomyomas or multicystic kidneys. A prenatal head MRI may be helpful after the 20th week of gestation to identify large cortical tubers.

Preimplantation and prenatal genetic tests are available and should be offered in addition to genetic counseling. Linkage studies of the entire family with affected and unaffected individuals may be done. Mutational analysis and multiplex ligation-dependent probe amplification have been used to assess genotype and phenotypic correlation.

In This Article

Historical note and nomenclature
Clinical manifestations
Clinical vignette
Pathogenesis and pathophysiology
Differential diagnosis
Diagnostic workup
Prognosis and complications
References cited