Adult progeria (Werner's syndrome)

Werner syndrome (syn.: adult progeria) is a rare autosomal recessive disease, gene locus - 8p12-p11. Life expectancy is reduced. The most common causes of death are myocardial infarction, cerebral stroke, malignant tumors.

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Epidemiology

It develops in people aged 15-20 years and is characterized by gradual progression.

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Causes adult progeria

The cause of the disease has not been established, metabolic disorders in connective tissue are possible, as indicated by a decrease in fibroblast proliferation, an increase in collagen production with a decrease in glycosaminoglycan synthesis. Slow fibroblast growth can be explained by changes in the composition of the intercellular substance.

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Pathogenesis

Histological examination of scleroderma-like plaques reveals slight atrophy of the epidermis with increased pigment content in basal epithelial cells. Homogenization of collagen is observed in the papillary layer of the dermis, and hyalinization and rarefaction of collagen fibers are observed in the reticular layer.

The number of vessels is reduced, some of them are surrounded by small inflammatory infiltrates consisting of lymphocytes and histiocytes with an admixture of plasma cells and eosinophilic granulocytes. The walls of the arteries are also hyalinized, the skin appendages are atrophic, especially the hair follicles and sebaceous glands, the sweat glands are unchanged. The elastic fibers of the reticular layer are fragmented.

There is a proliferation of connective tissue in the subcutaneous tissue, the newly formed collagen fibers are thin and loosely arranged. The nerve fibers consist of granular matter, are vacuolated, with pycnotic nuclei, and there is a proliferation of connective tissue along their periphery.

Electron microscopic examination reveals normal periodicity of collagen fibers, but between them are found clusters of amorphous substance or thin fibrils, which are immature collagen fibers; fibroblasts with signs of increased synthetic activity, as evidenced by numerous cytoplasmic outgrowths, expansion of the endoplasmic reticulum cisterns containing granular-fibrillar substance. Elastic fibers in different stages of maturity, vascular endothelial cells are often vacuolated.

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Symptoms adult progeria

Clinically, it is characterized by signs of premature aging, atrophy of the subcutaneous tissue and scleroderma-like changes in the skin of the acral localization, and bilateral cataracts.

Patients have a characteristic appearance: short stature, a moon-shaped face with a thin beak-like nose, pseudo-exophthalmos, a full body and thin limbs. On the bony protrusions and distal parts of the limbs there are areas of hyperkeratosis, diffuse hyperpigmentation or alternation of hyper- and hypopigmented areas, multiple pigment spots are possible. Trophic ulcers often appear on the feet and shins. Hair turns gray early and falls out. In addition to cataracts, eye damage in the form of keratoconjunctivitis and chorioretinitis is sometimes observed.

Bone changes are manifested by metastatic calcification, diffuse osteoporosis, and less commonly osteomyelitis.

There is an increased risk of developing diabetes mellitus and malignant skin neoplasms.

The sex glands are affected, which leads to hypogenitalism, testicular atrophy, menstrual irregularities, early menopause and underdevelopment of the mammary glands.

The most common mesenchymal malignant tumors are fibrosarcoma, leiomyosarcoma, liposarcoma, and leukemia. Melanomas, adenocarcinomas, basal cell carcinomas, and endocrine tumors are also observed.