Di George's syndrome is a birth defect caused by a loss of DNA material. At the root of this genetic disease is the loss of a fragment of chromosome 22, which results in the absence of about 50 genes. In patients there are, among others heart defects, immune disorders and hypoparathyroidism. How is Di George syndrome treated?

Di George syndrome , otherwise22q11 microdeletion syndrome , is the mutation that most often arisesde novo, i.e. it occurs in a child whose parents do not have it (it appears for the first time in the family), and is inherited only in about 5-10% of cases. The genetic defect develops around 6–8. week of pregnancy, is not dependent on gender and causes many physical and mental dysfunctions, and is also often associated with anomalies in appearance.

According to the European Registry of Birth Defects, the incidence of Di George's syndrome is 1: 9,700 live births. However, many scientific studies (e.g. in the study by Oskarsdottir, which compared the disease of the Swedish population in Gotland and in Gothenburg) confirmed a higher frequency of mutations depending on the diagnostic background.

What is Di George's syndrome?

Di George's syndrome is a genetic defect that was first described by Dr. Angelo Di George in 1968. This is the 22q11 microdeletion unit, which is also commonly referred to by other names that are used interchangeably. Among them there are :

  • Shprintzen's syndrome
  • CATCH22
  • Takao team
  • Sedlackov's team
  • VCFS team

It is worth emphasizing, however, that in many scientific articles one can still encounter inconsistency in the nomenclature and use of the above names as different defects, which is not appropriate.

Although, in fact, each of these diseases is characterized by slightly different symptoms and their severity, scientists have now unified the nomenclature and recommended that both Di George's syndrome and the above-mentioned names of very similar genetic diseases be referred to in the world by one common name as the 22q11 deletion or microdeletion complex.

90% of Di George's syndrome affects 48 genes, and the rest only 24 genes. As a result of lossof the above genes, during fetal development, many disorders affect the child's development, which after birth result in the appearance of mutation symptoms. Therefore, people who decide to have children and have 22q11 deletion syndrome should know that there is a 50% chance of passing the disease on to their offspring.

Importantly, research conducted in 2015 by Dona Landsman in Canada shows, however, that only 25% of pregnancies have a chance of delivering a he althy baby.

It is also important that the incidence of Di George's syndrome fluctuates as research into it is still ongoing. In addition, it should be remembered that many people remain undiagnosed and often either do not learn about the disease at all, or it takes place, for example, after the birth of offspring who are diagnosed with a genetic disease.

Di George's syndrome can cause not only many disorders, disabilities, and serious physical and mental he alth problems, but also miscarriages, death of infants and shorter life in adults.

Di George syndrome - causes

The main cause of Di George syndrome is a 22q11.2 deletion or microdeletion. This means that on the long arm of chromosome 22 (the smallest human chromosome in any cell in the body) there is a loss in the genetic material, which may include a short fragment of genes or a whole group of genes. The location of the site in the genetic fragment is defined as q11.2.

Another cause may also be a point mutation in the TBX1 gene, which is involved in the development of the heart, thymus, parathyroid glands and facial structures.

It is also possible that mutations in the HIRA / TUPLE1 and UFD1L genes are contributing to Di George's syndrome, but there are currently insufficient studies to conclusively confirm this.

Di George syndrome - symptoms

It should be emphasized that the number of symptoms and their severity differ depending on the examined case. Some patients may experience a genetic defect right after delivery, others later in life, and some may develop non-specific symptoms that may result in the fact that they are never correctly diagnosed.

It is worth noting, however, that scientists identified 180 symptoms that can be caused by 22q11 microdeletion syndrome, of which the patient most often has a maximum of 20

Di George's syndrome found in infants and newborns usually manifests as:

  • heart defects (occur in up to 82% of children)
  • food intake problems (difficulty sucking and swallowing)
  • cleft palate or other defects in it (ias a result, e.g. pouring through the nose)
  • hypotonic, i.e. low muscle tone
  • developmental delay, including cognitive, cognitive, speech, etc.

This happens very often:

  • weakened immunity (which is associated e.g. with frequent infections of the upper and lower respiratory tract)
  • poorly developed thymus (or lack thereof)
  • hypocalcemia (and associated hypocalcemic tetany)
  • malfunction of the parathyroid glands
  • inappropriate body weight and too short height

Children with this genetic defect often have ear infections, and therefore often suffer from hearing loss, which also adversely affects their development.

After childbirth, defects of the genitourinary system are also often found, including, for example :

  • kidney underdevelopment
  • renal cystic disease
  • hypospadias in boys

as well as nervous system defects, such as :

  • hydrocephalus
  • brain cysts
  • meningeal hernia

There are also digestive system disorders, including :

  • diaphragmatic hernia
  • anus defects
  • invalid bowel phrasing
Do you know that…

Di George's syndrome is the second most common cause of severe heart defect and developmental delay after Down's syndrome.

The flaws are also similar in terms of the presence of the characteristic features of the appearance, among others :

  • eyes wide apart
  • small and low set ears
  • fish-mouth
  • flat nose
  • differences in toe and foot length

In addition, both Di George and Down's syndromes are characterized by poor muscle tone.

Later in life, patients with Di George's syndrome are more likely to develop autoimmune conditions than he althy people. In addition, specialists confirm that there is also an increased frequency of Parkinson's disease among them.

Di George's syndrome also affects mental he alth, but although 80-100% of patients experience disorders related to it, they are rarely associated with Di George's syndrome. The resulting problems are most visible in adults, but they begin to develop already in childhood.

As a rule, children with Di George's syndrome are hyperactive, unable to concentrate, and have learning difficulties. They are also usually mildly mentally retarded.

In adults with this genetic defect syndrome, there is also a greater risk of developing mental illnesses, incldepression and bipolar disorder. Having this syndrome of mutations is also 30 times higher risk of schizophrenia compared to a he althy person. In addition, episodes of psychosis and dementia may also occur.

Di George's syndrome can also have nonspecific symptoms that may not be such a serious condition. They include, but are not limited to:

  • convulsions
  • anxiety disorders
  • curvature of the spine
  • hearing, speech and swallowing problems

How is Di George syndrome diagnosed?

The diagnosis of Di George's syndrome is not easy in many cases, and therefore some patients find out about it accidentally, for example when a child is born with a genetic defect. It is difficult to diagnose this disease because its symptoms are often not obvious and can be attributed to many diseases.

One way to make a diagnosis is through genetic testing. Unfortunately, microdeletions can occur randomly, so it is very difficult to predict what specific tests should be performed.

It is much easier to do them when the woman is still pregnant, and it is known that, for example, one of the parents has a mutation. In this situation, prenatal tests such as genetic amniocentesis are performed.

Prenatal diagnosis involves collecting amniotic fluid for examination. The procedure is performed between the 15th and 18th week of pregnancy.

However, you should be aware that the test is invasive, which is associated with possible complications (e.g. there is a 1% risk of miscarriage).

In later stages of life, the detection of a genetic defect is also possible during the diagnosis of other organs, e.g. the heart during echocardiography or X-ray examination of vertebral abnormalities in the cervical spine.

Di George syndrome - treatment

A person diagnosed with Di George's syndrome must be aware that it is a lifelong disease. From the moment of diagnosis, practically throughout his life, he must be under the constant supervision of specialists in various fields, including:

  • neurologist
  • cardiologist
  • gastroenterologist
  • endocrinologist
  • nephrologist
  • ENT specialist
  • psychologist
  • psychiatrists
  • immunologist
  • genetics

Thanks to this procedure, it is possible not only to minimize symptoms, but also to prevent their worsening and negative effects, as well as to recognize and treat new disorders. This is especially important in children with Di George's syndrome, because failure to apply appropriate therapies on time may adversely affect their development,not only physical, but also mental.

If the diagnosis is made immediately after the birth of a sick child, it is usually associated with starting treatment at that time and thus with many operations that help, among others, remove defects in the heart, digestive and nervous systems.

If the most serious symptoms are removed, the child often has to undergo specialist treatment, which, for example, improves hearing or minimizes speech problems.

Some patients require psychiatric treatment or psychological therapy to help minimize symptoms such as anxiety, hyperactivity, or treat conditions such as schizophrenia.

Pharmacological treatment is also often implemented in people with Di George's syndrome.

It is also worth remembering that the severity of symptoms in patients with Di George's syndrome may be variable, therefore, in addition to the constant control of specialists, there is also a need for constantly increasing awareness. Not only the patient should have knowledge about the disease, but also his relatives, which will help in understanding the disease and enable providing the necessary support.

Category:

Genetic diseases