Tuberous Sclerosis, A Simple Guide To The Condition, Diagnosis, Treatment And Related Conditions

This book describes Tuberous Sclerosis, Diagnosis and Treatment and Related DiseasesTuberous sclerosis complex (TSC) is a genetic disorder that is typically featured by hamartomas in many organs, but especially the skin, brain, eye, kidney and heart. Hamartomas are non-cancerous malformations comprising an overgrowth of the cells and tissues that normally happen in the affected area and include nevi (birthmarks).
It is inherited in an autosomal dominant manner and is characterized by a higher predisposition to hamartoma formation. It happens from mutations in the genes TSC1 and TSC2 and is known for causing neurological disorders such as epilepsy and intellectual disability. TSC is normally diagnosed in childhood or infancy, and the involved individuals may manifest with developmental delay, skin manifestations, or seizures.
Some presentations may be evident pre-natally, such as cardiac rhabdomyomas or cortical tubers. Other signs, such as osseous, renal or pulmonary lesions are often diagnosed in adulthood. The manifestation of the disease will differ depending on the developmental stage of the patient. While skin lesions are identified in 90% of patients of all ages, hypo-pigmented macules are normally present in early childhood.
CausesTuberous sclerosis is a genetic disorder from a mutation in one of 2 genes:1. TSC1, which produces a protein called hamartin (10-30% of cases)2. TSC2, which produces a protein called tuberinAbout one-third of all cases of tuberous sclerosis are inherited from an affected parent. All other cases are due to sporadic new mutations happening in the early stages of life, most often mutations of TSC2.
SymptomsA. Skin lesions are present in 60-70% of cases of tuberous sclerosis. AngiofibromasUngual fibromasShagreen patchOvoid or ash leaf-shaped white maculesB. Other organ involvementEpilepsy is evident in about 70% of patients with tuberous sclerosis. It normally starts in infancy or early childhood before the appearance of skin lesions by yearsDevelopmental delay and behavioral problems may also happen.1.
Mild to severe mental retardation, 2. Autism, 3. Attention deficit disorder (ADD), 4. Anxiety, 5. Depression, 6. Paranoia and7. Schizophrenia. Other signs and symptoms of tuberous sclerosis are:1. Eye involvement: white spots on the iris and white lumps on the retina2. Heart, gastrointestinal and kidney tumors3. Lung changesDiagnosisTuberous sclerosis is mainly diagnosed based on medical criteria but it can also be diagnosed with genetic testing.
Genetic testing of TSC1 and TSC2 is positive in 75% to 95% of patients affected with TSCThe diagnostic criteria for tuberous sclerosis involve these major and minor features:Major Features1. Hypo-melanotic macules (more than 2, and at least 5-mm in diameter)2. Angiofibromas (more than 2) or fibrous cephalic plaque3. Ungual fibromas (more than 1)4. Shagreen patch5. Multiple retinal hamartomas6. Cortical dysplasias7.
Sub-ependymal nodules8. Sub-ependymal giant cell astrocytoma9. Cardiac rhabdomyoma10. Lymphangioleiomyomatosis11. Angiomyolipomas (more than 1)Minor Features1. Confetti skin lesions2. Dental enamel Pitts (more than 3)3. Intra-oral fibromas (more than 1)4. Retinal achromic patch5. Multiple renal cysts6. Non-renal hamartomasTreatmentTuberous sclerosis is a multi-system disorder, so treatment from a team of doctors is necessary.
Laser treatment or electro-surgery can be done to remove angiofibromas. The topical mTOR inhibitor sirolimus 0.2% gel has proved useful in decreasing angiofibromasThe treatment of acutely symptomatic sub-ependymal giant cell astrocytomas (SEGA) is surgical resection. TABLE OF CONTENTIntroductionChapter ...