Monogenic Hereditary Diseases

There are different single-gene inheritance patterns:

– Autosomal dominant: the person only needs to receive the defective gene from one parent to inherit the disease. In these cases, anomalies usually appear in each generation and every affected child has an equally affected parent. Unaffected individuals do not transmit the disease. When one parent is affected, there is a 50 % chance of passing the disease to their children. Moreover, men and women have the same probability of suffering from it. Example: type 1 neurofibromatosis.

-Autosomal recessive: only individuals who inherit two copies of the affected gene (maternal and paternal) inherit the disease. I Individuals with one affected gene are carriers of the disease but do not express it. Example: cystic fibrosis.

X-linked dominant: dominant traits 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 mutated gene on their only X chromosome. Both sons and daughters of an affected mother have a 50 % chance of being affected, although the disease is generally milder in women than in men. Affected men only pass the disease to their daughters, their sons are healthy. Example: hypophosphatemic rickets.

-X-linked recessive: in these cases, if the woman is a carrier of an abnormal gene, she does not suffer from the disease because the normal X chromosome compensates for the anomaly. However, any male who receives the abnormal X chromosome will suffer from the disease. Each son born to a carrier woman of an X-linked recessive disease has a 50 % chance of inheriting the defective gene and, therefore, of developing the disease. Each daughter has a 50 % chance of inheriting the defective gene and being a carrier of the disease. Carriers usually do not show symptoms of the disease but may have an affected child. A man affected by an X-linked disease cannot pass the disease to his sons because he contributes the Y chromosome but he passes it to all his daughters, who are carriers.
Example: haemophilia.

-Y-linked inheritance: only males suffer from a Y-linked disease. Therefore, an affected male passes the disease to all his sons but none of his daughters. This type of inheritance is very rare.

• Cystic fibrosis
• α and β-thalassemia
• Fragile X syndrome
• Haemophilia A
• Spinal muscular atrophy
• Sickle cell anaemia
• Neurofibromatosis type 1 (NF1)
• Huntington’s disease
• Autosomal recessive polycystic
• kidney disease Myotonic dystrophy type 1 (Steinert’s disease)
• Duchenne/Becker muscular dystrophy
• Marfan syndrome

Couples who are carriers of a monogenic hereditary disease have a high risk of passing this condition on to their offspring, leaving them with few reproductive options. Until now, they could opt for adoption, IVF treatment with sperm or egg donors, or conceive a child with the disease and opt for therapeutic abortion. Preimplantation Genetic Testing (PGT) offers the possibility of having a child without transmitting the genetic disease. In couples at risk of transmitting a monogenic hereditary disease, PGT provides information on the status of each conceived embryo and allows only the healthy ones to be transferred to the maternal uterus.