Diagnosis and Management of Children With Tuberous Sclerosis Complex

Abstract

Tuberous sclerosis complex (TSC) is a multi-system autosomal dominant condition associated with disease-causing variants in either of the TSC1 or TSC2 genes. It can be associated with variable benign tumours (hamartomas) in different organs, most notably the brain, kidneys, skin and heart with different ages of onset. Affected children may have early-onset epilepsy, refractory epilepsy, varying degrees of developmental disability, ranging from normal cognition and learning difficulties to moderate-severe intellectual disability, neurodevelopmental disorders and mental health disorders. Multidisciplinary TSC-specific clinical care is recommended. A precision medicine (mechanistic target of rapamycin (mTOR) inhibitors) aimed at the early treatment of epilepsy and TSC-specific therapy for tumours can reduce the burden of the disease and improve clinical outcomes. We describe a multidisciplinary model of care for TSC, with an emphasis on the early detection and diagnosis of TSC and active surveillance/management of electrical seizures and clinical seizures. This review article will cover the following: clinical presentation and diagnosis of TSC, its genetic basis, the role of genetic counselling, pre-seizure surveillance of infants and TSC-specific (neurological, neurodevelopmental, renal, dermatological and pulmonary) management guidelines throughout life.

Keywords: early management; epilepsy; surveillance; tuberous sclerosis complex.