MONOGENIC HEREDITARY DISEASES

Definition

Monogenic hereditary diseases are those caused by alterations in the DNA sequence of a single gene.

Genes are small segments of DNA. They are arranged in order in the chromosomes, within the nucleus of the cells. Each cell has 23 pairs of chromosomes; two of them, the X and the Y, are the sex chromosomes and determine sex; the rest of chromosomes are called autosomal.

All genes serve as a pattern for the production of different proteins and together they provide the information needed to structure the body and its functions. When one of them is abnormal, it can produce an abnormal protein or also abnormal amounts of a protein that alter these functions.

Not always inherited abnormal traits have health consequences; Sometimes the consequences are minimal, but they can also produce alterations that lead to a significant decrease in the quality of life. Hereditary diseases affect 1-2% of the general population.

How are they transmitted?

There are different inheritance patterns of a single gene:

• Dominant dominant: the person only needs to receive the defective gene from one of the parents to inherit the disease. In these cases the anomalies usually appear in each generation and each affected child has an equally affected father. The unaffected people do not transmit the disease. When one of the parents is affected, the child has a 50% chance of inheriting the disease. In addition, men and women have the same probability of suffering it. Example: Neurofibromatosis type 1.
• Recessive-retrospective: Only individuals who inherit the two copies of the affected gene (maternal and paternal) will inherit the disease. Individuals with only one affected gene will be carriers of the disease, but will not express it. Example: Cystic fibrosis.
• Dominant linked to the X chromosome: The dominant characters linked to the X chromosome are rare. They manifest in women who have a mutation in one of the two copies of the gene on the X chromosome, and in men who have the gene mutated on the only X chromosome they have. Both sons and daughters of an affected mother have a 50% chance of being affected, although the manifestation of the disease is generally milder in women than in men. Affected males only transmit the disease to their daughters; their children will be healthy. Example: Hypophosphatemic rickets.
• Recessive linked to the X chromosome: In these cases, even if the woman is a carrier of an abnormal gene, she will not suffer from the disease, because the normal X chromosome will compensate the anomaly. In contrast, any male who receives the abnormal X chromosome will suffer the disease. Each male child born to a woman with a recessive disease linked to the X chromosome has a 50% chance of inheriting the defective gene and therefore of developing the disease. Each of the daughters will have a 50% chance of inheriting the defective gene and be a carrier of the disease. Carriers usually have no symptoms of the disease, but may have an affected child. A man affected by an illness linked to the X chromosome can not transmit the disease to his sons, because it provides the Y chromosome, but will transmit it to all his daughters, who will be carriers. Example: Hemophilia
• Y-linked inheritance: Only males will suffer a disease linked to the Y chromosome. Therefore, an affected male will transmit the disease to all his children, but to none of his daughters. This type of inheritance is very rare.

What are the most common hereditary diseases?

• Cystic fibrosis
• Α and β-Thalassemia
• Fragile X syndrome
• Hemophilia A
• Spinal Muscular Atrophy
• Sickle-cell anemia
• Neurofibromatosis Type 1 (NF1)
• Huntington’s disease
• Autosomal recessive polycystic kidney disease
• Type 1 myotonic dystrophy (Steinert)
• Duchenne muscular dystrophy / Becker
• Marfan syndrome

Reproductive options: Preimplantation Genetic Diagnosis

Couples carrying a monogenic hereditary disease have a high risk of transmitting this condition to their descendants, and therefore have few reproductive options. Until now they could opt for adoption, for an IVF treatment with sperm or egg donors or to conceive a child with the disease and opt for a therapeutic abortion. Preimplantation Genetic Diagnosis offers the possibility of having a child without transmitting the genetic disease.

What is the Preimplantation Genetic Diagnosis?

Although individuals carrying monogenic hereditary diseases do not necessarily have sterility problems, it is necessary to undergo in vitro fertilisation techniques to be able to analyse the embryos and select those that are healthy to transfer to the uterus.

Preimplantation Genetic Diagnosis (PGD) is a diagnostic method that is performed in the embryo before its implantation in the uterus. In couples at risk of transmitting a monogenic hereditary disease, PGD reports on the status of each of the embryos conceived, and allows only the healthy ones to be transferred to the maternal womb. The PGD technique is the result of the combination of in-vitro-fertilisation and genetic analysis.

What steps must be followed?

A geneticist must assess the couple’s reports. It is important to provide all the diagnostic tests that are available: complete genetic report detailing disease and mutation, family history, etc.

Later a study of informativity is carried out. To do this, a blood sample of the members of the couple (and in some cases) of another family member or carrier of that disease, accompanied by the corresponding genetic reports, is necessary. This test is a personalised genetic study for each couple in order to set up the technique that will be used to analyse the embryos, and determine whether the PGD is feasible or not. The study of informativity lasts approximately 2-3 months. Once the study is approved, the patient can already start the stimulation treatment for the in-vitro-fertilisation.

Are you a carrier of a hereditary disease and want a healthy baby?

You can contact us and we will clarify your doubts and inform you of the entire process.

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