Журнал «Здоровье ребенка» 2 (45) 2013

Tuberous sclerosis complex is a genetic disorder characterized by the growth of numerous noncancerous (benign) tumors in many parts of the body. These tumors can occur in the skin, brain, kidneys, and other organs, in some cases leading to significant health problems. Tuberous sclerosis complex also causes developmental problems, and the signs and symptoms of the condition vary from person to person. Virtually all affected people have skin abnormalities, including patches of unusually light-colored skin, areas of raised and thickened skin, and growths under the nails. Tumors on the face called facial angiofibromas are also common beginning in childhood. Tuberous sclerosis complex often affects the brain, causing seizures, behavioral problems such as hyperactivity and aggression, and intellectual disability or learning problems. Some affected children have the characteristic features of autism, a developmental disorder that affects communication and social interaction. Benign brain tumors can also develop in people with tuberous sclerosis complex; these tumors can cause serious or life-threatening complications. Kidney tumors are common in people with tuberous sclerosis complex; these growths can cause severe problems with kidney function and may be life-threatening in some cases. Additionally, tumors can develop in the heart, lungs, and the light-sensitive tissue at the back of the eye (the retina). Tuberous sclerosis complex affects about 1 in 6,000 people.

Mutations in the TSC1 or TSC2 gene can cause tuberous sclerosis complex. The TSC1 and TSC2 genes provide instructions for making the proteins hamartin and tuberin, respectively. Within cells, these two proteins likely work together to help regulate cell growth and size. The proteins act as tumor suppressors, which normally prevent cells from growing and dividing too fast or in an uncontrolled way. People with tuberous sclerosis complex are born with one mutated copy of the TSC1 or TSC2 gene in each cell. This mutation prevents the cell from making functional hamartin or tuberin from the altered copy of the gene. However, enough protein is usually produced from the other, normal copy of the gene to regulate cell growth effectively. For some types of tumors to develop, a second mutation involving the other copy of the TSC1 or TSC2 gene must occur in certain cells during a person's lifetime. When both copies of the TSC1 gene are mutated in a particular cell, that cell cannot produce any functional hamartin; cells with two altered copies of the TSC2 gene are unable to produce any functional tuberin. The loss of these proteins allows the cell to grow and divide in an uncontrolled way to form a tumor. In people with tuberous sclerosis complex, a second TSC1 or TSC2 mutation typically occurs in multiple cells over an affected person's lifetime. The loss of hamartin or tuberin in different types of cells leads to the growth of tumors in many different organs and tissues.

Tuberous sclerosis complex has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing tumors and other problems with development. In about one-third of cases, an affected person inherits an altered TSC1 or TSC2 gene from a parent who has the disorder. The remaining two-thirds of people with tuberous sclerosis complex are born with new mutations in the TSC1 or TSC2 gene. These cases, which are described as sporadic, occur in people with no history of tuberous sclerosis complex in their family.

Findings in TSC include the following: neurologic findings: abnormal neurologic findings result from the location, size, and growth of tubers and the presence of subependymal nodules (SENs) and subependymal giant cell astrocytomas (SEGAs); cutaneous findings: the best-known cutaneous manifestation of TSC is adenoma sebaceum, which often does not appear until late childhood or early adolescence; cardiac findings: cardiac involvement is usually maximal at birth or early in life; it may be the presenting sign of TSC, particularly in early infancy; 50-60% of individuals with TSC have evidence of cardiac disease, mostly rhabdomyomas; ophthalmic findings: at least 50% of patients have ocular abnormalities; some studies have reported a prevalence as high as 80%; these lesions are actually retinal astrocytomas that tend to become calcified over time; renal findings: renal manifestations of TSC are the second most common clinical feature; 4 types of lesions can occur: autosomal dominant polycystic kidney disease lesions, isolated renal cyst(s), angiomyolipomas (AMLs), and renal cell carcinomas; gastrointestinal findings: hamartomas and polyposis of the stomach, intestine, and colon may occur.

Laboratory studies are performed as indicated clinically to identify genetic mutations associated with TSC, monitor anticonvulsant treatment, identify idiosyncratic or dose-related adverse effects, and identify or monitor underlying renal or pulmonary disease. Diagnosis should be possible in most cases using established clinical criteria. The following imaging studies are usually undertaken in patients with TSC: computed tomography scanning or magnetic resonance imaging of the brain, renal ultrasonography, echocardiography, electroencephalography, electrocardiography. There is no specific treatment for tuberous sclerosis. Because the disease can differ from person to person, treatment is based on the symptoms. Genetic counseling is recommended for couples who have a family history of tuberous sclerosis and who want to have children. Prenatal diagnosis is available for families who are known to have a history of this condition.

Сlinical observation. Girl presented with complaints of shortness of breath, pale nasolabial triangle, with increasing anxiety, seizures, skin rash. She is ill from birth. In the period 32 weeks pregnant at the time of ultrasound examination revealed changes in the heart, with the assumption that the rhabdom, tuberous sclerosis. On echocardiography in the neonatal period are confirmed multiple rhabdomyomas. At 2 weeks of age, the girl suddenly appeared in the form of an attack of convulsions tonic tension legs and throwing back her head, first one every 2-3 days, followed by more frequent up to 5 times a day. She was repeatedly in the neurological hospital with a diagnosis of "Tuberous sclerosis, symptomatic epilepsy, West syndrome, frequent infantile spasms, delay of psycho-motor and physical development. Rhabdomyoma of the heart". Receiving anticonvulsants with little short-term effect. On the ECG recorded supraventricular paroxysmal tachycardia with heart rate 270 per minute, and therefore directed to our clinic. An objective examination of the child's condition was serious due to the phenomena of respiratory failure and neurological symptoms. Drowsiness during the day. Person was with hypertrophic cheeks. At the time of examination was marked tremor of the chin and abduction gaze toward lasting no more than 15 seconds. Head does not hold, mother's voice responds. Pale skin, on the left hip irregular patches of depigmentation 0.5-1 cm in diameter. In the navel two bright pink rash element with a shiny surface, towering above the skin. Tachypnea to 70 in 1 minute with the auxiliary muscles. Rhythmic activity of the heart, tones were weakened, heart rate – 160 beats / min. Echocardiography – plural formation in the apex of 0, 6 x0, 7 cm in the right ventricle, in the middle third of the interventricular septum 0,4 x0, 42cm and 0,43 x0, 45 cm without obstruction of the heart chambers and blood vessels (rhabdomyomas?). Myocardial satisfactory. 24-hour Holter monitoring: during the observation sinus rhythm with a heart rate 118-163/min., mean heart rate 137/min., WPW-phenomenon, type B. The MRI of the brain – multiple polymorphic focal changes caused by the primary disease – fakomatozom ( tuberous sclerosis). Computer-EEG – low-amplitude slow-wave EEG with no signs of local disease. Functional immaturity. Conclusion genetics – tuberous sclerosis.

This case demonstrates the severity of the tuberous sclerosis with early appearance of neurological symptoms, changes in the cardiovascular system and skin manifestations.