Tuberous sclerosis (TSC) is a genetic neuro-cutaneous disorder characterized by formation of benign tumors, especially affecting the skin and the central nervous system. The tumors are usually either benign hamartias or hamartomas. Only very rarely, are cancerous hamartoblastomas encountered. Dermatological features include the presence of hypomelanotic macules, depigmented spots, ashlead pattern depigmentation, shagreen patches, and/or growth under the nails. Tumors within the brain result in neurological symptoms, including seizures (tonic, clonic, myoclonic, and infantile), behavioral problems, developmental delays, learning disabilities, mental retardation, and features of autism. Behavioral problems, such as attention deficit hyperactivity disorder, aggression, obsessive compulsive disorder, and hyperactivity are fairly common. Tumors may also be seen affecting the kidneys, heart, and lungs. Angiomyolipomas are frequently seen in the kidneys. Cardiac manifestations are in the form of arrythmias, rhabdomyoma, or atrial septal defect. It is estimated that TSC affects about one in 6,000 people.
Diagnosis of TSC is on the basis of the clinical symptoms and features, and on the presence of a family history for this condition. Physical examination, as well as CAT, MRI, and ultrasound scans are utilized for confirming the diagnosis. Genetic testing is also now available for detecting the disease.
Unfortunately, there is no cure for TSC. Symptomatic treatment, however, is available. Seizures are controlled by anti-epileptic medications, and behavioral problems and learning disabilities can be overcome by special schooling and occupational therapies. Skin lesions can be managed with the help of surgical treatment. Prognosis is fairly good for people with mild symptoms. However, in patients with the severe form of the disease, affecting the kidneys and brain, the condition may be fatal.
The TSC genes are responsible for the development of tuberous sclerosis. At least four different genes are recognized: TSC1, TSC2, TSC3, and TSC4. Tuberous Sclerosis 1 is linked to the TSC1 (chromosome 9) gene, which encodes hamartin.
Hanna et al. (1997) reported an 18 year old Kuwaiti female suffering from bilateral perinepheric angiomyolipomas (AML) that correlated with tuberous sclerosis. The subject, admitted at Al-Sabah Hospital, experienced large bilateral perinpheric tumors, with renal involvement, pulmonary changes, and demonstrated the classical features of tuberous sclerosis including epileptic fits, adenoma sebaceum and retinal phakomata. According to Hanna et al. (1997), this was the second case which reported an association among bilateral perinpheric AML and tuberous sclerosis.
Al Sabti et al. (1997) reported the features of 13 children (seven females and six males; mean age at presentation: 6 years) diagnosed with tuberous sclerosis according to the established criteria of seizures, skin lesions, other systemic lesions and findings in CT scan of the brain. All children were clinically examined, and investigated with routine blood investigations and scans. Clinically, all children had fits and skin lesions, while nine (69.2%) had mental retardation and four (30.8%) had delayed milestones. Family history was found in two cases (one had an affected brother, while the other had two affected siblings and an affected father). In three patients, there was cardiac involvement (ASD in one who also had choanal atresia, septal nodule with thickening of LV wall in another, and rhabdomyoma in the third patient). Retinal hamartoma was found in one patient. Brain CT scan findings indicated that 11 had abnormal scans with calcified subependymal glial nodules (three of these had other calcifications as well) detected in ten, while one had hypodense lesions. Three patients had normal EEG, but out of the other 10, five had focal spikes (38.5%), two had generalized seizures, while non-specific slowing of the bodyguard activity was detected in three patients. Various antiepileptic drugs were used to treat these children.
[Al Sabti H, Alexander PC, Koul RL, Jeans WD. Tuberous sclerosis in children. Oman Med J. 1997; 14(2):18-21.]
Al-Hwiesh et al. (2005) reported two Saudi brothers with familial tuberous sclerosis in comorbidity with Fanconi Syndrome. In both cases, there were histories of failure to thrive and mental retardation associated with hypokalemic metabolic acidosis.
Alorainy (2006) reviewed and analyzed the MRI studies on 808 pediatric patients (aged 3 days to 15 years) over a 3-year period. A total of 114 congenital cerebral malformations were identified in 86 of these patients via MRI. One patient was identified with Tuberous Sclerosis.