Tuberous sclerosis

Tuberous sclerosis (synonyms: Pripglia-Burpevelli disease, Burnedelli van der Heve fakomatosis, etc.) is a hereditary disease characterized by hyperplasia of ecto- and mesodermal derivatives. Type of inheritance is autosomal dominant. Mutant genes are located in the loci 16p 13 and 9q34 and encode tuberins - proteins that regulate the GT-phase activity of other extracellular proteins.

Causes of the tuberous sclerosis

Tuberous sclerosis is a multi-systemic disease with the defeat of ectoderm derivatives (skin, nervous system, retina) and mesoderm (kidney, heart, lungs). Inheritance is autosomal dominant with variable expressiveness and incomplete penetrance. A linkage with the llql4-1 lq23 locus was established. Probably the presence of other defective genes, in particular, located on the 12th and 16th chromosomes. Up to 86% of cases are the result of new mutations, however, with a thorough comprehensive examination of relatives of patients, including skull tomography, eye and kidney examination, the number of hereditary forms increases.

[1], [2], [3]

Pathogenesis

In angiofibroma proliferation of fibroblasts, proliferation of collagen fibers, formation of new vessels, expansion of capillaries, absence of elastic fibers are noted. In hypopigmental spots there is a decrease in melanocytes and sizes of melanosomes, a reduced melanin content in melanocytes and keratinocytes.

Pathomorphology

Angiofibromas consist of a large number of small vessels, often with enlarged lumens, located in a dense connective tissue with a large number of cellular elements. Over time, the sebaceous glands become atrophic and even disappear completely. The number of hair follicles, however, is often increased, sometimes they are immature. Soft fibromas histologically have a typical picture of fibroid, but without a vascular component. In the region of the shagreen foci, in the lower part of the mesh layer of the dermis, massive proliferation of homogeneous collagen fibers is seen that resembles scleroderma. The elastic fibers in these places are fragmented, the vessels and appendages of the skin are absent. In ultrastructural research, dense compact bundles of collagen fibrils are detected, among which there are single curved or twisted fibrils located among the fine-fiber substance, possibly the precursor of collagen. In the foci of hypopigmented spots, although a normal amount of melanocytes is noted, there is no pigment in them, as well as in epithelial cells. In melanocytes of white spots, electron microscopic examination revealed a decrease in the size of melanosomes, a decrease in the content of mature melanin. In milky-white spots, melanosomes are found only in the initial stages of development, as in skin-eye albinism.

Histogenesis is still unclear, but there is an increase in the sensitivity of lymphocytes and fibroblasts in patients with tuberous sclerosis to ionizing radiation, which may indicate a disruption in DNA repair processes and explain the frequency of occurrence of new mutations.

[4], [5], [6], [7], [8], [9],

Symptoms of the tuberous sclerosis

The disease begins in childhood or adolescence. Skin is affected in 96% of cases. Characteristic of the presence of nodules the size of a pinhead to a pea, located symmetrically in nososchnechnyh folds, on the chin, in the parotid region. Nodules round, oval in shape, flattened, brownish-red, usually closely adjacent to each other, sometimes merge, stand above the surrounding skin. Their surface is smooth, often with telangiectasia. On the trunk are marked "shagreen" plaques, which are a connective tissue nevus. They are slightly raised above the surface of the skin, soft, with a bumpy surface resembling the skin of an orange. There are okolonogte fibromas (Kenen's tumor) - tumors or nodes on the nail roller. 80% of patients have hypopigment white with yellowish or grayish tinge spots, located on the trunk, legs, arms and neck.

Clinically, the classic triad of symptoms: angiofibroma, mental retardation and epilepsy. There is a symmetrical arrangement of angiofibromas on the face, mainly in the area of nasolabial folds, on the cheeks, chin, less often on the forehead and scalp. They are small reddish nodules with a smooth surface, appearing usually in childhood, and occur in 90% of patients over the age of 4 years. In addition to angiofibrom, fibroma, shagreen foci, "coffee with milk" spots, hypopigmented spots, subungual and peri-nasal fibroids and nodules on the oral mucosa are found on the skin.

Soft pale pink or brown tumorous or in the form of plaques of various sizes of fibroids are usually located on the forehead, scalp and upper cheeks. Shagreen-shaped foci along with angiofibromas are the most frequent cutaneous manifestations of tuberous sclerosis. They are detected in almost all patients older than 5 years in the form of flat raised foci of various sizes, having the color of normal skin and a surface of the "lemon peel" type. They are usually located in the lumbosacral region. The stains of coffee and milk, as shown by the studies of SD Bell and DM MacDonald (1985), are equally common in patients with tuberous sclerosis and in healthy individuals, and therefore have no diagnostic value. In contrast, hypopigmented spots are important for diagnosis. They usually resemble the shape of a leaf, pointed on one side and rounded off on the other, and have a pale gray or milky-white color. People with light skin spots can only be seen with the help of a Wood lamp. They exist from birth and with age only increase in size. The combination of spots with epileptiform seizures in children is of diagnostic importance. Subungual and peri-nasal tumor-like formations are fibromas or angiofibromas. Retinal tumors - phacomas, or astrocytic hamartomas - are also one of the most common manifestations of tuberous sclerosis. Although they are non-specific, they are characteristic of Tuberous Sclerosis, therefore eye examination is necessary in all cases if Tuberous Sclerosis is suspected. Another characteristic feature is the intracranial calcifications detected by X-ray examination, which gave the name "tuberous sclerosis". Convulsive seizures are often the earliest symptoms of the disease and are regarded as epilepsy before the onset of skin symptoms. Less frequent manifestations of tuberous sclerosis are abnormalities of the skeleton, rhabdomyoma, nervous system tumors, visceral organs and disembryoplasia.

The full-scale clinic of the disease also includes vnutritserebralnye calcifications, retinal tumors, hemarthros and cysts of the kidneys, liver hemarthros, rhabdomyoma of the heart.

Differential diagnosis

Hypo-pigmentation spots should be distinguished from the focal form of vitiligo, anemic nevus, pityriasis. Angiofibromas differentiate from trichoepithelioma, syringioma.

[10], [11], [12], [13], [14], [15]

Treatment of the tuberous sclerosis

Nodules are removed by laser or electrocoagulation.

Forecast

The prognosis depends on changes in the brain, internal organs.

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