BHD and Tuberous sclerosis (TSC) – Part I: Overview

Tuberous sclerosis (TSC) is a rare genetic disease that causes benign tumours to grow in vital organs such as the kidneys, heart, eyes, lungs, and skin.  It commonly affects the central nervous system.  In addition to these, other common symptoms include seizures, mental retardation, behaviour problems, and skin abnormalities.  TSC may be present at birth, but signs of the disorder can be subtle and full symptoms may take some time to develop.

Currently, there is no cure for TSC, although treatment is available for a number of the symptoms. Antiepileptic drugs may be used to control seizures and medications may be prescribed for behaviour problems. Intervention programs, including special schooling and occupational therapy, may benefit individuals with special needs and developmental issues. Surgery, including dermabrasion and laser treatment, may be useful for treatment of skin lesions. Since TSC is a lifelong condition, individuals need to be regularly monitored by their medical practitioner and since there is no ‘typical’ TSC patient, care by an expert in disorder is recommended.

The clinical similarities between BHD and TSC suggest that Folliculin and TSC proteins may function within a common pathway. The TSC proteins inhibit the activity of the mammalian target of rapamycin complex 1 (TORC1), and in Schizosaccharomyces pombe, FLCN and Tsc1/Tsc2 have opposing roles in the regulation of amino-acid homeostasis (Ref). Since there is significant phenotypic overlap with these two syndromes and both are entrenched in the mTOR pathway, what can we learn from the comparisons between these syndromes? More to follow….