Progeria of adults (Werner's syndrome)

Werner's syndrome (syn: progeria of adults) is a rare autosomal recessive disease, the gene locus is 8p12-p11. Lifetime is reduced. The most common causes of death are myocardial infarction, stroke of the brain, malignant tumors.

[1], [2], [3], [4], [5]

Epidemiology

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

[6], [7], [8], [9], [10], [11], [12]

Causes of the progeria adults

The cause of the disease is not established, there may be metabolic disorders in the connective tissue, which is indicated by a decrease in the proliferation of fibroblasts, an increase in collagen production with a decrease in the synthesis of glycosaminoglycans. Slow growth of fibroblasts can be explained by changes in the composition of the intercellular substance.

[13]

Pathogenesis

Histological examination of scleroderm-like plaques shows a slight atrophy of the epidermis with an increase in the pigment content in the basal epitheliocytes. In the papillary layer of the dermis, homogenization of collagen is noted, in the mesh layer - hyalinization and rarefaction of collagen fibers.

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 hyalineized, the appendages of the skin are atrophic, especially the hair follicles and sebaceous glands, sweat glands are not changed. The elastic fibers of the mesh layer are fragmented.

There is a proliferation of connective tissue in the subcutaneous tissue, the newly formed collagen fibers are thin, loosely arranged. Nerve fibers consist of a granular substance, vacuolated, with pycnotic nuclei, along the periphery of which there is a proliferation of connective tissue.

Electron microscopy examines the normal periodicity of collagen fibers, but between them clusters of amorphous substance or thin fibrils, which are immature collagen fibers, are revealed; fibroblasts with signs of increased synthetic activity, as evidenced by numerous cytoplasmic outgrowths, expansion of endoplasmic reticulum cages containing a granular fibrillar substance. Elastic fibers in different stages of maturity, vascular endotheliocytes are often vacuolated.

[14], [15], [16], [17]

Symptoms of the progeria adults

Clinically characterized by signs of premature aging, atrophy of the subcutaneous tissue and scleroderm-like skin changes of the ablation localization, bilateral cataracts.

Patients have a characteristic appearance: low growth, moonlike face with a thin beak-like nose, pseudo-exophthalmos, full trunk and thin limbs. On bone protrusions and distal limbs - areas of hyperkeratosis, diffuse hyperpigmentation or alternation of hyper- and hypopigmented sites, multiple pigmented spots are possible. On the feet and legs, trophic ulcers often occur. Hair turns gray early, falls out. In addition to cataract, eye damage is sometimes observed in the form of keratoconjunctivitis, chorioretinitis.

Changes in bones are manifested by metastatic calcification, diffuse osteoporosis, less often osteomyelitis.

There is an increased risk of developing diabetes and malignant tumors of the skin.

The sex glands are affected, which leads to hypogenitalism, testicular atrophy, menstrual cycle disorder, early menopause and mammary maldevelopment.

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