Patient Information
What is genetic testing?

A genetic test is a test of your DNA (deoxyribonucleic acid) that provides instructions for the functions of each cell in your body. Various changes (mutations) in DNA can lead to the manifestation of genetic disease in prenatal, neonatal, early childhood, or later age.

Genetic diseases are caused by various changes in the structure of DNA called mutations. These changes can affect whole chromosomes, such as aneuploidy (e.g. trisomy - carrying an extra chromosome; monosomy – lack of a chromosome), small fragments of the chromosomes (microdeletions/microduplications), or can affect single nucleotides from DNA (point mutations). Most genetic diseases are inherited. Sometimes, for the manifestation of a particular genetic disease, both parents must carry a specific genetic variant/mutation (recessive inheritance). In other cases, the inheritance of a pathogenic genetic variant from only one parent is a sufficient condition for the occurrence of the disease (dominant inheritance). There are cases in which the mutation occurs de novo in the patient, such as the chromosomal aneuploidies and severe monogenic diseases with poor prognosis.

By conducting a genetic test, a genetic diagnosis can be made in the presence of a variety of symptoms in different organs and systems; the genetic test is used to confirm a presumed clinical diagnosis; to clarify the risk of developing the disease in relatives in the family and of transmitting a known mutation in subsequent pregnancies; to choose the right therapy, individual dosage of the medication and prophylaxis, etc.

When is a genetic test needed? (according to the list - when it is done)

Genetic testing is needed for:

  • Diagnostic clarification - clarification of the diagnosis in case of suspicion of a genetic disease (genetic diagnosis)

  • Pharmacogenetics - determining the response to certain drugs, as well as their dosage in accordance with the genotype of the individual

  • Predictive testing - related to the use of a specific treatment and the ability of the individual to respond to that treatment

  • Presymptomatic genetic testing - with a recurrent family history and high risk of developing the disease in the offspring and direct relatives

  • Presence of an unclear syndromic condition in early neonatal and / or childhood

  • Prenatal diagnosis - genetic testing of the fetus with ultrasound indication findings for congenital anomalies, intrauterine retardation and / or abnormal results from biochemical screening and suspicion of genetic disease

Interpretation of a genetic test result

The interpretation of the results of a genetic testing is performed by a genetic consultant. Different genetic methods have different diagnostic possibilities. The results can be negative (normal) or positive (with a genetic variant found).

Negative results are interpreted in the context of the specific method used for specific genetic defects. A negative result does not exclude the possibility of the presence of a genetic disease, but only means that the patient does not carry the specific genetic defect for which he was examined.

If the results of a particular genetic test are positive (genetic variant found), there are several possibilities for interpretation. The LGD works with criteria for classifying the genetic variants found according to those proposed by the American College of Medical Genetics (ACMG (1)). According to them, genetic variants are divided into variants with pathogenic effect, likely pathogenic variants, variants with unclear clinical significance, likely benign and benign (normal) variants.

Pathogenic genetic variants - the variant should be absent in the population databases and should be present in the databases, containing variants detected in sick individuals with similar clinical characteristics. Many prediction programs define the genetic variants as disrupting protein structure and function.

Probably pathogenic variants - the identified variants are considered as the probable cause of the patient's disease, as prediction programs determine a protein-disrupting effect and the variant has a very low frequency in the control population. There is still not enough information in the literature for them to be classified as pathogenic variants. The discovery of a likely pathogenic variant should be used with caution in making clinical decisions, because there is still some degree of uncertainty for its pathogenicity.

Variants of unclear clinical significance - this group of variants is the most numerous. There is not enough information collected about them so far in order to unambiguously determine their pathogenicity. This group include newly discovered variants with an unproven effect, which at a later stage could be classified as probably pathogenic or probably benign. According to ACMG criteria, in order to be assigned to one of the two groups, they must meet at least 90% of the classification criteria of these two groups. In the future, it is possible that the pathogenicity of variants of unknown significance to be re-evaluated on the basis of gathered information and data from experimental and clinical studies.

Probably normal (benign) - the variant has a low population frequency (less than 1%), but is probably not the cause of the studied disease because it occurs in healthy individuals and has no proven effect on protein function.

Normal (benign) variants - occur with a high frequency in healthy individuals of the population, there is no segregation in the affected family members (healthy relatives also carry the mutation), prediction programs define the variant as neutral on protein function.

Genetic counseling

Modern genetic counseling is a process of communication between health professionals in genetics and an individual or family affected by a genetic disease or at risk of developing one. The aim is to understand the medical and genetic nature of the disease, determine the role of heredity and the risk of recurrence, discuss options for dealing with the disease and help the family make the decision that is most appropriate for them.

Genetic counseling can be done in person, with couples or with whole families. In all cases, the patient and family members must have prepared the results of all clinical and laboratory tests in advance. If necessary, a blood sample can be taken from one or more than one family member.

If the analysis is complete, the results are discussed during the genetic consultation. It includes a discussion of the potential effect of the result on the family planning and on the health of the patient. The patient is also informed about the possibilities of potential therapy of the given genetic disease.

Indications for genetic counseling:

- Clinical indications: proven or suspected hereditary disease or one with a hereditary predisposition in a child or relative (monogenic, polygenic, chromosomal); mental, physical and sexual retardation; congenital malformations, isolated or syndromic (neural tube defects, microcephaly, macrocephaly, hydrocephaly), abnormalities of the cardiovascular, digestive and urinary systems, facial dysmorphism, clefts of the mouth and palate, etc.

- Preclinical indications: healthy heterozygous carriers of mutations for autosomal recessive (AP), X-recessive (XP) diseases, detected by massive or selective screening; asymptomatic newborns with metabolic disorders detected by neonatal mass massive or selective screening, etc .; carrying a balanced chromosomal rearrangement (translocation, inversion); pregnant women at high genetic risk for Down syndrome of the fetus, detected by massive biochemical screening or other indications (ultrasound findings for fetal morphological abnormalities).

- Reproductive disorders: two or more miscarriages; premature births and stillbirths; families with infertility; women with amenorrhea, hypoovarism, underdeveloped secondary sexual characteristics.

- Blood marriage, increasing the risk of giving birth to children with autosomal recessive diseases.

- Age indicator - advanced age of women over 35 years and men over 45 if there is a will to reproduce.

- Familial forms of malignant diseases.

- Teratogenic and mutagenic effects during pregnancy - X-rays, medication, past infections, etc.

The indications for genetic counseling can be permanently supplemented in order to discover new methods of diagnosis, prevention and treatment of hereditary diseases.

Preliminary preparation for genetic counseling

Part of the genetic counseling involves compiling a family tree and identifying affected family members. It would be very useful if there is preliminary information about the health problems of the relatives in the family.

If there are preliminary clinical tests related to your illness or the illness of your relative, please bring the results with you. This includes: epicrisis, previous genetic or clinical-laboratory tests, results of histological and imaging, etc.

Prenatal screening and prenatal diagnosis

These tests provide information to the future parents whether their child is at risk of developing or suffering from a specific genetic disease. They include routine screening and diagnostic tests.

Screening tests are non-invasive routine procedures performed during the first to third trimester of pregnancy. These tests include the examination of biochemical parameters in the mother's blood through prenatal biochemical screening and ultrasound fetal morphology. Screening tests can assess the risk (likelihood) of developing a disease. When the results of these tests are abnormal, it is necessary to perform diagnostic genetic tests to determine the presence or absence of a corresponding disease in the fetus.

Diagnostic tests are invasive tests with a very low risk for miscarriage (0.5-1%). These tests analyze fetal DNA isolated from fetal cells obtained by chorionic villus sampling (between 10 and 12 weeks of gestation) or amniocentesis (after 16-19 weeks of gestation) and aim to identify unbalanced chromosomal abnormalities or DNA mutations leading to the manifestation of a genetic disease.

Indications for performing diagnostic prenatal DNA tests are:

• abnormal screening test result (calculated high risk of biochemical screening or detection of ultrasound anomaly)

• presence of chromosomal aberration in previous pregnancies

• intrauterine fetal retardation

• mother's age over 35 years

• family history of a specific genetic disease

LGD offers the following prenatal diagnostic tests (link):

  • Test 132 - Congenital abnormalities and malformative syndromes / spontaneous abortions

  • Test 134 - Prader Willi / Angelman syndromes – Large deletions/insertions and rearrangements and methylation profile in genome region 15q11- PWS/AS

  • Test 135 - Russell-Silver/Beckwith-Wiedemann syndromes - Large deletions/insertions and rearrangements and methylation profile in genome region 11p15BWS/RSS