Genodermatoses is a common name for a heterogeneous group of hereditary diseases with predominant skin lesions. They are characterized by a significant polymorphism of clinical manifestations, are divided into 6 groups according to phenotypic signs and the main mechanism of development. Specific symptoms include foci of hyper- or hypopigmentation, areas of increased keratinization and scaliness of the skin, cutaneous tumor formations. The diagnostic plan consists of clinical, biochemical, histological and molecular genetic methods. Supportive treatment is determined by the type of genodermatosis, the severity of symptoms.
ICD 10
Q80 Q81 Q82
General information
There are about 200 genetically determined skin diseases, which account for 35% of hereditary nosologies, up to 10% of all dermatological diseases. The lesion of the skin may be the only manifestation of pathology, but more often it occurs in combination with multi-organ disorders. Genodermatoses are a serious problem in modern dermatology, which is caused by the complexity of their treatment, the lack of etiopathogenetic therapy, and an increased risk of tumors in a number of skin diseases.
Causes
True genodermatoses have a monogenic nature — they develop when a certain gene is mutated in somatic or sex chromosomes. By the nature of inheritance, the autosomal dominant variant is in the first place, when it is enough for a child to develop a genetic anomaly from one parent, and the risk of the syndrome is 50% for infants of both sexes. Autosomal recessive, X-linked types of inheritance are less common.
In multifactorial genodermatoses, exogenous provoking effects are necessary for the manifestation of the process. Common triggers include endocrine disorders (pathologies of the hypothalamus, epiphysis, thyroid gland), chronic foci of infection (tonsillitis, caries, rhinosinusitis), allergic disorders. Important provoking factors are increased psycho-emotional stress, unfavorable environmental situation.
Pathogenesis
Given the large variability of diseases included in the group of genodermatoses, it is not possible to identify typical pathogenetic features. At the heart of most pigment disorders is an increased sensitivity of skin cells to UV rays, against which foci of hyperpigmentation are formed. Genodermatoses, manifested by hypopigmentation, occur with a decrease or absence of melanin production due to mutations of the corresponding enzymes.
Ichthyosis is characterized by disorders of the processes of skin keratinization, slowing the exfoliation of dead keratinocytes, which is accompanied by thickening and changing the appearance of the skin. With tumor skin syndromes, pathogenesis is associated with mutations of genes responsible for suppressing the growth of neoplasms, as a result of which patients face multiple benign neoplasms.
Classification
In the Russian medical literature, the division of diseases into 10 groups according to the localization and nature of the lesion is widespread. In international dermatological practice, classification is more often used taking into account the mechanism of development and phenotypic manifestations of genodermatoses, according to which the following forms are distinguished:
- Genodermatoses with impaired DNA repair: xeroderma pigmentosa, Werner syndrome, Rotmund-Thomson syndrome.
- Genodermatoses with impaired keratinization: ichthyosis, congenital dyskeratosis, epithelial nevus syndrome.
- Genodermatoses with lentiginous hyperpigmentation: Peitz-Jaegers-Touraine syndrome (hamartomic gastrointestinal polyposis).
- Genodermatoses with skin hypopigmentation: albinism, Germansky-Pudlak syndrome.
- Bullous genodermatoses: epidermolysis bullosa.
- Hereditary tumor syndromes: neurofibromatosis, tuberous sclerosis, Cowen, Gardner, Muir-Torre syndromes.
Multifactorial diseases that are characterized by hereditary predisposition are distinguished in a separate category, but their manifestation requires the negative influence of external factors. This group includes psoriasis, atopic dermatitis, vitiligo. A large heterogeneous group is represented by congenital metabolic disorders, which are accompanied by skin lesions, such as Niemann-Pick disease, phenylketonuria, homocystinuria.
Symptoms
Most diseases manifest themselves in the first months after the birth of a child. Alarming signs are pathologies of gestation, premature birth, symptoms of intrauterine development of the fetus. Some nosologies, for example, Werner’s disease, manifest in adults, the peak of their diagnosis falls at the age of 20-30 years.
Genodermatoses with pigmented disorders
Genodermatoses occurring with hyperpigmentation are characterized by areas of photodermatitis, freckles and large brown spots on open areas of the child’s body, dryness and hyperkeratosis. With the progression of the process, areas of atrophy, depigmentation, deformation of the auricles, the tip of the nose appear. In those suffering from albinism, on the contrary, there is an unnatural pallor of the skin, a reddish tinge of the pupils, the absence of pigment in the hair, eyelashes, eyebrows.
Genodermatoses with keratinization disorders
Genodermatoses from the ichthyosis group have pathognomonic manifestations: an abundance of dense scales on the skin, which give the appearance of snake skin. The scales have a dark brown color, are tightly bound to the epidermis, are practically not removed during hygienic procedures and rubbing with a washcloth. Congenital dyskeratosis is characterized by dystrophic changes in the nails, leukoplakia of the mucous membranes.
Tumor genodermatoses
With phacomatoses (tumor syndromes), a combination of skin signs with damage to the nervous system is characteristic. Multiple painful neoplasms of a dark pink or brown hue appear on the body, reaching a diameter of several centimeters. Along the course of the nerve trunks, numerous flat tumors are also probed. Pathognomonic skin pigmentation in the form of milk-coffee spots.
Complications
Genodermatoses, as a rule, are accompanied by an eye lesion of the type of blepharitis, keratitis, ectropion. Corneal ulceration, papillomas, basal cell carcinoma of the eyelid are less common. The most dangerous complication of most tumor and pigmented skin changes is a high risk of malignancy — the formation of malignant neoplasia. They are the main cause of death in patients with genodermatoses.
With some hereditary dermatoses, for example, hamartomic polyposis of the gastrointestinal tract, many internal organs are involved in the process. Such patients suffer from multisystem disorders that determine the severity of the condition. Usually nosologies are combined with neuropsychiatric disorders: children have attention deficit hyperactivity disorder (ADHD), autism spectrum disorders, problems with socialization due to atypical appearance.
Diagnostics
The basis of the diagnosis is a clinical examination of the patient by a pediatric or adult dermatologist. When identifying typical signs (areas of hypopigmentation, dense scales, bullous rashes), it is possible to establish a preliminary diagnosis in order to purposefully carry out laboratory and instrumental diagnostics of the problem. Then a set of diagnostic measures is prescribed:
- Histology of the skin. The main research method, which is used to study the microstructure of the skin, the detection of excess pigment cells, hyperkeratosis, thinning of the germ layer. In most diseases, swelling, inflammatory infiltration of the dermis is determined.
- Additional instrumental methods. Often, genodermatoses are combined with somatic pathology. Therefore, imaging studies are shown to patients. In neoplastic syndromes, CT or MRI of the brain is necessarily performed. To assess the structural and functional features of the gastrointestinal tract, ultrasound of the abdominal cavity and radiography are recommended.
- Biochemical analyses. In keratoses, the activity of STS in leukocytes is studied, serum protein electrophoresis is performed to differentiate different forms of ichthyosis. Immunofluorescence, immunohistochemical techniques play a valuable role in clarifying the causes of genodermatoses.
- Genetic testing. Examination of the patient’s genome is the most accurate diagnostic method. Methods of exon or genome sequencing, fluorescent hybridization (FISH) are used. Since studies are expensive and time-consuming, they are prescribed according to strict indications if it is impossible to establish a diagnosis in other ways.
A number of monogenic skin pathologies are subject to diagnosis even in the prenatal period, if the parents are sick or are carriers of mutant genes. Ultrastructural analysis of fetal skin biopsies, determination of galactosidase activity in amniotic fluid, and examination of the level of steroid sulfatase are used for prenatal detection of genodermatoses. If necessary, the biomaterial is genotyped after amniocentesis, chorion biopsy.
Treatment
Since pathologies are caused by mutations in the genetic apparatus of cells, there is no etiopathogenetic treatment. Diseases require lifelong maintenance therapy in order to control the intensity of skin manifestations, normalize the well-being of patients, and, if possible, eliminate unaesthetic foci on the skin. The treatment program includes the following areas:
- Selection of melting cosmetics. To care for damaged skin, products with keratolytics, softening and nourishing components, organic acids are used. Topical steroids and local retinoids are recommended for some diseases.
- Protection from the sun. Ultraviolet light is the main trigger for the development of malignant skin tumors in genodermatosis, so in the warm season it is mandatory to apply creams with SPF 30-50 on all exposed areas of the body. With albinism, you need to wear contact lenses or glasses that block UV rays.
- Minimally invasive techniques. With benign tumor formations, it is possible to remove them using electrocoagulation, cryodestruction, laser radiation. Dermabrasion and other cosmetic procedures may be prescribed to improve the condition of the skin.
Prognosis and prevention
Although genodermatoses cannot be completely cured, many of them can be successfully controlled by maintenance therapy in order to minimize clinical symptoms and improve the quality of life of patients. The prognosis is less favorable for patients with neoplastic syndromes, which often end in death from malignant neoplasms, as well as burdening genodermatosis with severe metabolic or somatic systemic pathologies.
Taking into account the hereditary nature of diseases, the basis of prevention is medical and genetic counseling of couples from risk groups in the period of conception planning. If there is information about severe familial genodermatoses, it is advisable to conduct prenatal screening or preimplantation genetic diagnosis (when undergoing IVF protocol). To prevent complications, lifelong special skin care, dispensary observation by a dermatologist is required.
