Diagnosis of genetic diseases

What is a genetic disease?

Genetic disease is a condition caused by a change in chromosomes or genes that can be inherited from generation to generation. There are several thousand inherited genetic diseases. Often their symptoms are similar, although the diseases are caused by mutations in different genes. Most genetic abnormalities that cause disease occurs in a part of the genome which encodes proteins. The “Herzliya Medical Center” uses an advanced laboratory where genetic diseases can be diagnosed.

What is the genetic consultation?

The process of genetic counseling includes meeting with a physician-geneticist. During the meeting, a doctor clarifies the history of the disease, performs a syndromic diagnosis, discusses whether the disease is genetic and can be inherited. Diagnosis is carried out using special methods of laboratory study: cytogenetic, molecular genetic and biochemical. When a diagnosis of genetic disease and its hereditary nature are confirmed, physician consults members of the family, inform about the nature of the condition, prognosis of its course, the possibility of treatment, the risk of the disease in family members and the possibility of this risks elimination or minimization. In the field of children’s diseases, genetic counseling is essential if genetic syndromes include multiple malformations, mental retardation, autism, growth retardation, central nervous system problems, and other diseases.

Prenatal genetic counseling

Only a few numbers of genetic diseases can be successfully treated. Nowadays, the development of genomic technologies allows carrying out routine genetic screening for hundreds of different mutations. This approach is already revolutionizing our ability to prevent the birth of children suffering from severe, incurable genetic diseases. Thus, preventive detection of couples who have an increased risk of a baby with a genetic disease is crucial. Every healthy person is a carrier of several genetic mutations, but he does not know about it. For couples planning a pregnancy or for women in the early stages of pregnancy, we offer genetic counseling and genetic tests to identify carriers of genetic diseases common in the general population, such as fragile X chromosome syndrome, cystic fibrosis, spinal muscular atrophy, and others. These tests are recommended for all couples planning a pregnancy, including those with no history of genetic diseases in the family.

Recommendation for the test before or during early pregnancy is associated with the ability to perform prenatal diagnosis of fetal via amniocentesis or chorionic villus sampling, which can prevent the birth of a child with severe genetic diseases.

Besides, we recommend prenatal genetic counseling at the Institute of Genetics of the private clinic “Herzliya Medical Center” in the following cases:

• Age of pregnant women for more than 35 years;
• Pathological findings of prenatal screening for chromosomal abnormalities, executed in the first trimester (the thickness of the nuchal fold of the fetus, PAPP-A, and free beta HCG) and the second trimester (AFP, HCG, UE3) pregnancy;
• When fetal ultrasound study revealed irregularities in its structure and development;
• The family has a member with the suspected congenital or hereditary disease;
• The family has a member with mental retardation;
• Infertility and repeated miscarriage;
• Closely related marriages.

Genetics in Pediatrics

More than 3% of children are born with various types of congenital malformations or genetic diseases. The goal of genetics pediatrician is to prevent complications of the disease in a childcare and family planning in the next pregnancy, to prevent the birth of other children with similar pathology. In some cases, the precise genetic diagnosis can lead to a specific treatment.

We offer genetic counseling for the following indications:

• Mental retardation or delayed psychomotor development of children for an unknown reason, dysmorphism, autism;
• Congenital malformations;
• Neurodegenerative diseases;
• Deafness, blindness;
• Muscular dystrophy;
• Suspicion of other monogenic diseases such as cystic fibrosis, Marfan’s disease, neurofibromatosis, polycystic kidney disease, spastic paraplegia, tuberous sclerosis, spinocerebellar ataxia, genetic skin diseases and other genetic diseases;
• Chromosomal abnormalities;
• Syndromes caused by microdeletions and microduplications;
• Short stature, skeletal dysplasia.

Herzliya Medical Center offers the following diagnosis of genetic diseases:

• Karyotyping;
• Chromosomal microarray (CMA)
• Sequencing any gene or genes panel
• Exome sequencing (WES or WXS)

Chromosomal microarray (genomic microarrays)

Using routine karyotyping allows identifying major chromosomal changes. In recent years, genomic technology has been developed, which allows diagnosing submicroscopic changes in the number of copies of the genome with higher resolution compared to the routine karyotyping. This technology is called chromosomal microarray or genome chip. It is used to evaluate the number of DNA copies at the single-gene level.

What benefits has diagnosis using genetic microarray?

Clinical benefits of identifying the cause of disease using the genetic microarray include:

• Determining a more accurate prognosis for a child;
• In some cases, it allows using of specific treatment;
• Confirming the exact risk of genetic disorders in future children;
• Opportunity to prenatal diagnosis or in vitro fertilization with the preimplantation diagnosis.

Exome Sequencing

Exome sequencing for clinical application is already introduced in the standard practice of clinical diagnostics. This technology is used to confirm the diagnosis of diseases caused by genetic mutations. The analysis allows sampling of blood to check the genetic alterations in 20,000 genes, and, therefore, it is a very effective diagnostic method. Nowadays exome sequencing is most useful for detecting mutations in patients with a phenotype that is changed in a single gene. Exome sequencing allows detecting all the genes coding for proteins. This analysis can not only replace many expensive standard tests but also greatly increase the chances of genetic mutations detection.

What benefits can Exome Sequencing bring for diagnostics?

There are many clinical benefits of identifying genetic mutations. Firstly, an application of techniques for the exome sequencing diagnosis gives results faster and cheaper than other types of diagnostics. Secondly, in some cases, the precise genetic diagnosis may lead to a certain treatment. Thirdly, after the proof of the exact genetic cause of the disease, it is possible to determine a more accurate prognosis. Identification of the genetic mutation allows you to set the risk of disease recurrence in future children and allows for prenatal diagnosis or in vitro fertilization with preimplantation diagnosis, as well as the parents and other family members.

Who should be diagnosed by Exome Sequencing?

Using the diagnosis of genetic diseases by Exome Sequencing, all pathological changes can be found in the genome of a patient’s. The purpose of this test is to provide comprehensive genomic examination cheaply and much more efficient than sequential analysis using target panels for a specific group of diseases (e.g. mental retardation, neuropathy, muscular dystrophy, genetic disorders of the central nervous system, the specific panel of cardiac disease, and so forth). Physicians must correctly identify the indications for diagnostic using the Exome Sequencing. The decision to use Exome Sequencing for a particular patient should include the following key elements: the collection of information about the family history, a systematic assessment of species heredity and clinical symptoms of the patient and review of the medical literature and databases. It is necessary to determine whether the manifestation of disease meets the diagnosed clinic syndrome. It is important to understand how to select the right patients so that they can benefit from this examination. It is necessary to know exactly how to order the test and interpret the results. Selects strategy for family members undergoes the test depend on the expected inheritance patterns (e.g., dominant or recessive). In some cases, it is important to check the health of relatives.

Each patient’s exomes includes multiple variants of DNA. However, many of these DNA variants is normal. Determination of the options that cause genetic diseases requires necessary assessing the clinical information properly. Most laboratories are used well-known methods such as Sanger sequencing for confirmation of positive exome sequencing results.

Sometimes using Exome Sequencing can identify brothers and sisters at-risk, for which screening or prophylactic treatment may improve clinical outcomes.