By Zaira Salvador BSc, MSc (embryologist) and Antonio Alcaide Raya BSc, MSc, PhD (senior embryologist).
Last Update: 11/12/2018

Monogenic diseases are caused by a single gen mutation in the DNA sequence of a person. This type of diseases affect the quality and lifespan of people affected because they can cause birth defects, intellectual, sensory, or motor disability. Unfortunately, there is no treatment or cure for monogenic diseases.

Genetic diseases are hereditary, which is to say, they can be transmitted from parents to children. Depending on each disease, the inheritance pattern can be dominant or recessive. Simply put, parents can be unaffected carriers of the disease.

Nonetheless, unaffected carrier parents may conceive a sick child. In these cases, the only solution available to prevent it is by undergoing In Vitro Fertilization (IVF) with Preimplantation Genetic Diagnosis (PGD).

Autosomal dominant diseases

Genetic diseases of autosomal dominant inheritance manifest in a single copy of the defective gene, called allele. This is inherited by one of the parents as well, which means that he or she is sick, too.

Thus, the chances of transmitting an autosomal dominant disease are 50% depending on whether the child inherits the healthy or altered allele from his/her parents.

The following are the most common autosomal dominant diseases worldwide:

Myotonic dystrophy

Myotonic dystrophy type 1 (DM1), also known as Steinert’s disease, is the most frequent type of dystrophy in adults.

The most common symptoms in those who suffer from this disease are weakness and muscle rigidity (inability of the muscles to relax normally). It also affects other parts of the body, including the heart (arrhythmia and conduction blockage), eyes (cataracts), and pancreas (diabetes).

Sleep disorders and depression are frequent in people with Steinert’s disease as well.

Myotonic dystrophy type 1 can appear anytime during a person’s lifetime, either at birth or during adulthood.

Huntington disease

Huntington disease (HD), also known as Huntington’s chorea, is a severe neurological disease characterized by progressive cognitive deterioration.

Most people affected by this disease develop it at adult age, generally between ages 35 and 55. It typically progresses slowly and gradually until death. The average lifespan is 15 to 20 years, although it varies from person to person.

In the United States, there are approximately 30,000 symptomatic inhabitants, and more than 200,000 at-risk of inheriting HD. (Source: Huntington’s Disease Society of America)

The affected gene causing the disease is the one responsible for codifying the huntingtin protein, also known as HTT or HD. As a result of this mutation, this protein is produced massively in neurons, causing their death at some parts of the brain.

Nonetheless, the disease itself is rarely the cause of death of people affected by it. They typically pass out as a result of health issues caused by body weakness, such as choking, infections, or heart failure.

Marfan syndrome

Marfan syndrome is a rare genetic disease that affects connective tissue, resulting in abnormalities of different structures of the skeleton, lungs, eyes, heart, etc.

The cause of Marfan syndrome is a genetic mutation that affects the fibrillin gene, one of the proteins that form the connective tissue and supports the skin, bones, blood vessels, and different organs.

Marfan syndrome has several grades of severity. However, typical symptoms include: very tall height, thin body, and flexible joints.

Moreover, people affected by this syndrome can have cardiovascular problems, such as leaking heart valves and aortic aneurysm; abnormalities like scoliosis, arachnodactyly, etc.

Neurofibromatosis types I and II

Neurofibromatosis (NF) is a multisystem genetic disorder that affects the development and growth of nervous cell tissue.

As a result, people affected by NF develop benign soft tissue tumors that can develop anywhere across the nervous system: brain, bone marrow, or nerves. Other alterations, including skin abnormalities or bone deformities, may appear as well.

Based on the gene that is mutated, we can distinguish two types of NF:

NF1
It typically appears during childhood. Most common symptoms include cutaneous findings, like café-au-lait spots, axillary freckling, bone deformities, unusually large head size (macrocephaly), short stature…
NF2
Also known as central neurofibromatosis, it is less frequent than NF1. It is characterized by non-cancerous tumors of the nerves of the inner ears, causing headache, significant hearing loss, buzzing, balance problems, etc. Tumors may appear in other nerves of the body, such as the optic or spinal nerve, as well as the brain, or peripheral nervous systems.

As explained earlier, there exist no permanent cure for these genetic diseases, only treatments to relieve the symptoms and improve the life quality of people affected by them.

Autosomal recessive diseases

Genetic diseases of autosomal recessive inheritance characterize for the presence of mutations in both alleles. Simply put, symptoms of an autosomal recessive disease show only if this condition is met.

In other words, for a child to develop an autosomal recessive disorder, he or she must have a copy of the affected gene from the father, and another one from the mother. Thus, the risk of transmitting this type of diseases to offspring is 25% if both parents are hereditary carriers.

A carrier of an autosomal recessive disease is a person that has only one defective allele. This is the reason why they do not show symptoms of it.

The following sections are brief summaries of each one of the most common autosomal recessive genetic disorders nowadays:

Fanconi anemia

Fanconi anemia (FA) characterizes for the presence of hematologic abnormalities, affecting the bone marrow above all. As a result, the person affected has diminished levels of all kinds of blood cells: red blood cells, white blood cells, and platelets.

The most common complications that could arise in people with this condition are anemia, infections, blood clotting disorders, etc. Moreover, they are more likely to develop hematological cancer, including acute myeloid leukemia (AML).

The lifespan of people affected by FA is 30 years approximately.

Spinal muscular atrophy

Spinal muscular atrophy (SMA) is a rare neuromuscular disorder that makes the muscles weaker, causing progressive muscle wasting.

This disease affects the part of the nervous system that controls voluntary muscle movement. It leads to failure of the nervous impulses to reach the muscles, which tend to atrophy.

The progressive loss of motor neurons affects the ability to walk, breathe, swallow, speak, and control the head and neck of the affected individual.

The life expectancy of people with SMA depends on the particular type and how it affects the breathing function. Some forms of SMA are fatal, and unfortunately there is no cure for any of them to date.

Cystic fibrosis

Cystic fibrosis (CF) causes thickened mucus to form in the lungs, causing lung damage and making it hard to breathe, especially if it blocks the airways.

Mucus can form in the pancreas, liver, and intestine as well, which can be fatal due to the number of persistent infections associated.

In the United States, over 30,000 people are living with CF, and more than 70,000 worldwide. Moreover, about 1,000 new cases of cystic fibrosis are diagnosis each year. (Source: Cystic Fibrosis Foundation Patient Registry)

The CFTR gene is the one responsible for the onset of CF. Mutations in this gene lead to failure in cell transportation and location of the CFTR protein, causing the mucus that covers the lungs and other organs to be thicker and stickier than normal.

Beta thalassemia

Beta thalassemia (BT) is a disease that causes an abnormal production of hemoglobin, a type of protein that is part of blood cells, and is in charge of transporting oxygen to the different body tissues.

The most severe form of BT is known as Cooley’s anemia. A person that is affected by this disease can show symptoms as early as few months following birth. It causes the patient to be dependent on blood transfusions.

BT is one of the causes why many couples decide to have another child that is genetically compatible with a sick older sibling. The goal is that he or she donates bone marrow to the sick sibling, thereby becoming a savior sibling. Learn more: What Are Savior Siblings & How Are They Created?

Gender related genetic diseases are due to abnormalities in the genes on sexual chromosomes X or Y. This type of mutations can be transmitted following an autosomal dominant or recessive inheritance pattern, although X-linked diseases are more frequent.

The following sections will provide you with details about the most common male- or female-specific disorders:

Retinitis pigmentosa

The medical term retinitis pigmentosa (RP) actually refers to a group of genetic disorders that involve a breakdown and loss of cells in the retina. It has several inheritance patterns: autosomal dominant, autosomal recessive, and X-linked.

It causes retinal degeneration and death of rod cells (photoreceptor cells that are used in peripheral vision). In the most severe degrees of RP, it also affects cone cells (photoreceptor cells in the retina that dominate central vision), which causes blindness in almost all cases.

People affected by RP find it very hard to see in dim and dark light. It is characterized by a progressive loss of the field of vision until the person affected experiences “tunnel vision”.

One should note that RP is a slow-onset disease. For this reason, it is commonly diagnosed several years after having the first symptoms.

In the USA, about 81,000 to 108,000 people have RP or a related disorder. With a worldwide population currently estimated at over 7.05 billion, it can be estimated that approximately 1.77 to 2.35 million people have one of these disorders. (Source: National Organization for Rare Disorders)

Check out this for more information: Retinitis Pigmentosa (RP) – Symptoms, Causes & Treatment.

Fragile X syndrome

It is the main cause of hereditary cognitive impairment, affecting males in a greater proportion than females. It is estimated that 1 out of 4,000 men have this disease, whilst 1 out of 600 females are hereditary carriers.

Fragile X syndrome is a disease linked to the X chromosome, and caused by a mutation in a DNA segment of the FMR-1 gene. As a result, the protein that is codified by this gene is not produced, and therefore it cannot carry out its function.

Some clinical manifestations of the fragile X syndrome are long and narrow face, large ears, enlarged testicles, and, as mentioned above, cognitive impairment and developmental problems.

Duchenne and Becker muscular dystrophy

Muscular dystrophies form a group of recessive diseases linked to the X chromosome, and characterized for a progressive muscular wasting and loss of muscle mass.

Even though there exist many types, the most common are Duchenne and Becker muscular dystrophies. Both affect males above all, and have similar symptoms, although they differ on the onset of the disease, as well as on the grade of severity and stages of development.

Duchenne muscular dystrophy
The most frequent of all. It affects 20-30 children out of every 100,000 males born, and has an early onset, namely between ages 2 and 6. It has a rapid progression and the life expectancy is 20-30 years on average.
Becker muscular dystrophy
The symptoms are not so severe, and it has a late onset, namely during childhood or even adulthood. The progression pattern tends to be slow, and the life expectancy of these individuals varies depending on the severity of the symptoms and the type of breathing and/or heart problems that it causes.

The mutations that cause this group of diseases are those affecting dystrophin, a key protein for stabilization and protection of muscle fibers. Thus, the lack of dystrophin causes muscle cells to be unprotected and progressively damaged.

Hemophilia

Type A and B hemophilia are recessive genetic diseases linked to the X chromosome. They cause blood clotting problems, and they are more common in males.

Type A hemophilia is characterized by a deficiency in blood clotting factor VIII, while type B is caused by missing or defective factor IX.

Clinical symptoms of hemophilia include spontaneous or heavy bleeding from even minor injuries.

IVF cycle with PGD

The ultimate goal of Preimplantation Genetic Diagnosis (PGD) is to prevent the transmission of genetic disorders that could severely affect the health of offspring.

PGD is a genetic screening of embryos created in IVF cycles. Out of all the embryos screened, only those that are healthy are selected for the transfer or cryopreserved for future cycles.

The PGD process begins by analyzing informative markers in the intended parents with the purpose of detecting the particular mutation causing the genetic disease.

The analysis of informative markers is used to determine if PGD is useful or not in a particular case considering the mutation, and whether the tools available can be used in that individual case. This process can be extended to up to 2-4 months.

Indeed, as Antonio Alcaide Raya, BSc, MSc, PhD states, PGD is actually able to detect all kinds of genetic pathologies as long as the gene causing each is known.

You may also enjoy some further information reading this: How Does the PGD Process Work?

It should be noted that, broadly speaking, conducting an analysis of monogenic diseases combined with numerical disorders in chromosomes allows embryologists to get more accurate results with PGD.

FAQs from users

Which genetic diseases can be prevented with PGD for gender selection?

By Zaira Salvador BSc, MSc (embryologist).

Recessive genetic disorders linked to the X-chromosome such as Duchenne muscular dystrophy (DMD), hemophilia, color blindness, fragile X syndrome (FXS), etc.

It is also possible to prevent certain diseases associated with the Y-chromosome, including but not limited to, azoospermia factor (AZF) microdeletions.

What is the difference between chromosomal disorders and monogenic disorders?

By Zaira Salvador BSc, MSc (embryologist).

Monogenic or monogenetic diseases are caused by mutations on a single gene of an person’s DNA sequence. On the other hand, chromosomal diseases, also known as aneuploidies or chromosomopathies, are caused by alterations in the number and structure of the chromosomes, such as in the case of Down syndrome, Edwards syndrome, translocations, inversions, etc.

Get more info: What Genetic Diseases Can PGD Test for?

Suggested for you

Monogenic diseases are just a group of genetic disorders that can be detecting by using IVF with PGD. To learn more about the different disorders that can be detected using this technique, read: What Genetic Diseases Can PGD Test for?

PGD can be used for gender selection of embryos as well, whether for therapeutic or social reasons, depending on the country and the regulations governing the use of this method. Learn more: Gender Selection – Can You Actually Choose Your Baby’s Sex?

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References

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Handyside AH, Kontogianni EH, Hardy K, Winston RM. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 1990;344:768–70

Harper J. Introduction to preimplantation genetic diagnosis. In: Harper J, editor. Preimplantation genetic diagnosis. 2nd ed. Cambridge: Cambridge University Press; 2009. p. 1–47

Spits C, Sermon K. PGD for monogenic disorders: aspects of molecular biology. Prenat Diagn 2009;29:50–6.

Van Rij MC, De Rademaeker M, Moutou C, Dreesen JC, De Rycke M, Liebaers I, et al. Preimplantation genetic diagnosis (PGD) for Huntington’s disease: the experience of three European centres. Eur J Hum Genet 2012;20:368–75.

Wein N, Alfano L, Flanigan KM. Genetics and emerging treatments for Duchenne and Becker
muscular dystrophy. Pediatr Clin North Am. 2015 Jun;62(3):723-42.

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Authors and contributors

 Zaira Salvador
BSc, MSc
Embryologist
Bachelor's Degree in Biotechnology from the Polytechnic University of Valencia (UPV). Embryologist specializing in Assisted Procreation, with a Master's Degree in Biotechnology of Human Assisted Reproduction from the University of Valencia (UV) and the Valencian Infertility Institute (IVI). More information
License: 3185-CV
 Antonio Alcaide Raya
BSc, MSc, PhD
Senior Embryologist
Bachelor's Degree in Biology and Accreditation of Expert on Medical Genetics. Master's Degree in Biology and Developmental Embryology from the University of Valencia (UV). Member of Directive Board of ASEBIR and laboratory director at clinic ReproFiv. More information
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