KHARKOV NATIONAL MEDICAL UNIVERSITY Prevention of inherited pathology

KHARKOV NATIONAL MEDICAL UNIVERSITY

Prevention of inherited pathology. Genetic counseling and prenatal diagnosis. Abu Elenin Ahmed 5 th course 2 nd group

During last 20 years the inborn and inherited diseases became significant in incidence of population. Negative factors: - increasing influence of factors of environment - spreading of chronic and infection pathology - low level of prevention - absence of succession between specialists - increasing of genetic loading of populations.

Positive factors: - spreading of knowledge on medical and clinical genetics (Specialized Medical Genetic Center, Scientific Research Institutions, Universities); -program of genetic monitoring of inborn developmental defects and chromosomal diseases; -program of prevention and early detection of inborn and inherited diseases; - improvement of methods of diagnostics (mitochondrial diseases, heterochromatine diseases, organic acidurias )

Maintenance of the child with invalidating inborn or inherited pathology is more expensive in 4 -10 times than modern diagnostics and treatment. This group of diseases influences on indexes of incidence, invalidation, and mortality (50% are died in childhood). All these reasons make the problem of prevention of genetic defects as one of the actual problems of genetics and medicine.

Three levels of prevention of genetic defects

Primary – measures on prevention of pathological conception and development of disease by the way of decreasing receptivity and removal factors of risk.

Secondary level – measures directed on prevention of development of the disease through the early diagnostics and adequate treatment. These measures are provided in prenatal period.

Third level – measure directed on sick people. Their aim is prevention of progressing of the diseases and development of complications of inborn and inherited diseases through the adequate treatment and rehabilitation.

Pregametic level: - health protection of population of reproductive age (qualitative prophylactic medical examination, succession of observation); - environmental protection (limitation or removal of mutagenic, teratogenic, and toxic influences).

Inherited changeability is usually added by new mutations. 20% of inherited diseases – result of spontaneous mutations. These are casual and unforeseen events.

Mutational loading of population Inherited diseases (5% of newborns) Lethality Mortinatality Ruin of zygotes in Spontaneous Early children’s (1% of preimplantation period abortions (15% of mortality (0, 5% of pregnancies) (60% of not registered children before 1 pregnancies) years old)

Ecological situation on the planet is grounded anxious. Every day the number of harmful factors increases physical chemical biological nature More than 60000 denominations of harmful matters are found in the water, ground, air, and foodstuffs. In some regions about 1000 t of solid sediments is thrown into atmosphere for a person annually.

Factors of inducted mutagenesis Radial affects: gamma rays; roentgen rays; quick neutrons; alpha-parts. 2. Medical preparations: cytostatics; antimetabolites; immune depressants;

-anticonvulsive preparations; psychotropic preparations; hormones; mixes for anesthesia; anti-inflammatory agents (butadionum, paracetamolum, amidopirin) bactericidal, disinfectant agents.

3. Chemical matters: synthetic compounds; organic dissolvent; salts of hard metals; pesticides; dyes for hair; cosmetic additions; food dyes; preservatives.

4. Smoking (increasing of frequency of sister chromatid metabolism depending on number of smoked cigarettes is established in smokers). 5. Alcohol (weak mutagenic action). 6. Persisting viral infections (cytomegalovirus, herpes, viruses of rubella, measles, parotitis, hepatitis etc. ). 7. Disorder of somatic status (saccharic diabetes, disease of thyroid and parathyroid glands, adrenal glands, phenylketonuria, galactosemia etc. ).

Tasks of pregametic prevention register - limitation - removal of factors of inducted mutagenesis Sanitation of life conditions Excluding and limitation of professional harms Sparing character and volume of providing treatment and investigation of patients Refusal from harmful habits

Correction of immunity, vaccination (parotitis, rubella) Estimation of health condition of future parents (chronic inflammatory processes of genitals, urinary paths etc. should be treated in time, because the disease, its treatment and disorder of homeostasis have negative influence on reproductive function).

The first place in the structure of children’s mortality, invalidity, and mortality due to IP belongs to inborn developmental defects (IDD), they are also the reasons of great number of embryonic and fetal mortalities. On data of the World Health Organization (WHO) the birth rate of children with IDD is 4 -6%.

Expenses for treatment and care for children with IDD aren’t justified due to severity of consequences of IDD. That’s why the development of prevention of IDD is in the range of the most actual problems of Health Protection. IDD – structural, metabolic and functional disorders of an organ, a part of body or large site of body appearing intrauterine.

Depending on term of action of media factors there are: Gametopathies: inherited syndromes, as a result of mutations in sexual cells of parents. Blastopathies: IDD of the type of double defects, cyclopias, syrenomelias appearing in affection of blastocyst – embryo of the first 15 days of life. Embryopathies: IDD conditioned by teratogenic factors from 16 -th day to 8 -th week of the pregnancy. Phetopathies: rare DD (dystopias, hypoplasias) conditioned by fetal affections in the period from 9 -th week to end of the pregnancy.

INTERNATIONAL CLASSIFICATION OF INBORN DEVELOPMENTAL DEFECTS

Ш By frequency: Ш common (> 1 : 1000 newborns) Ш moderate frequent (0, 1 -0, 99 : 1000 newborns) Ш very rare (< 0, 01 : 1000 newborns) Ш By severity: Ш lethal (death before reproductive age, usually after birth immediately) - 0, 6% Ш moderate severity (isn’t a threat for life, but requires a surgical intervention) -1, 9 -2, 5%

Ш Small developmental anomalies or informative morphological variants (haven’t any serious medical or cosmetic consequences) 3, 5% Ш On manifestation: Ш isolated (monotopic defect of field, polytopic defect of field) Ш multiple (syndrome, association and casual combinations) Ш On etiology: Ш monogenous — 6% Ш chromosomal - 5% Ш environmental (teratogenes, maternal factors) -6% Ш multifactor-63% Ш unknown reasons - 20%.

Some important postulates: Affection of embryo in preimplantation period in reversible affection of cells leads to recovery of embryo; in irreversible one – to death. Embryonic period – development of organs and systems from embryonic germ. It’s provided in interaction of embryonic genome and maternal organism, her endocrine and immune system. These mechanisms can be disturbed under action of teratogenes.

Deadline term of formation of any organ during of which an affecting factor can lead to developmental defect in embryonic period is a termination teratogenic period.