What is DiGeorge Syndrome?

DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a genetic disease that is present from birth. The main reason is the defect in one of your chromosomes, 22q11.2. This defect is a missing piece of chromosome 22. This missing piece is responsible for developing your midline structures in the embryonic phase, including your thymus and parathyroid glands. Therefore, your thymus and parathyroid glands do not properly develop in this syndrome.

Causes of DiGeorge Syndrome

Chromosomes are located in the nucleus of cells and are inherited from parents to offspring. They contain much information about average growth and development and transmit it to the next generation. When chromosomes become defective or missing for any reason, it causes various developmental anomalies. In DiGeorge syndrome, segment 11 of chromosome 22 is missing on its long arm q, and it causes severe abnormalities like learning difficulties, congenital cardiac defects, and abnormal facial features. Also, the third and fourth pharyngeal pouches fail to form thymus and parathyroid glands in your embryonic phase, causing T cell dysfunction and hypocalcemia, respectively.¹

How is DiGeorge Syndrome Transmitted?

DiGeorge syndrome typically arises from spontaneous genetic mutations during fetal development rather than being directly inherited from parents. In rare cases, it can be inherited from a parent with a chromosomal rearrangement involving chromosome 22. However, most cases occur sporadically due to de novo mutations. This defective gene leads to several abnormalities in your organs, like the heart, parathyroid, or thyroid gland.

Symptoms of DiGeorge Syndrome

This syndrome is often associated with a spectrum of features summarized by the acronym CATCH 22:

C: Cardiac defects
A: Abnormal facies (distinctive facial features)
T: Thymic hypoplasia or aplasia (underdevelopment or absence of the thymus gland, leading to immune deficiencies)
C: Cleft palate or other palatal abnormalities
H: Hypocalcemia (low calcium levels in the blood due to underdeveloped or absent parathyroid glands)

The number “22” refers to the deletion on chromosome 22, specifically at the 22q11.2 location, which causes the syndrome.²

Symptoms vary from person to person. In most cases, you don’t even present with symptoms; however, you can still be the carrier of this genetic mutation. Symptoms are:

Developmental Delays & Learning Difficulties:

DiGeorge syndrome presents mild to moderate brain symptoms. It involves learning disabilities and behavioral modifications in a child. It leads to anxiety and depression due to its long-term course. In severe cases, it might cause seizures and hallucinations. Moreover, the typical developmental milestones of a child are affected, and they cannot grow normally physically as well as mentally.

Cardiac Anomalies:

This syndrome severely affects your heart and presents with the following congenital diseases:

Tetralogy of Fallot:
In TOF, there is a ventricular septal defect, transposition of great vessels, overriding of the aorta, and pulmonary stenosis. Its early symptoms are blue skin and difficulty breathing.
Truncus Arteriosus:
It is a congenital disease of the heart in which the aorta and pulmonary arteries do not separate during the developmental phase of your life in utero. Heart surgery is the only permanent cure for this disease.
Narrowing of the Aorta:
The aorta is the largest vessel in your body, and when it becomes narrow, the blood cannot flow properly through the aorta’s small walls. This condition causes high blood pressure.
Transposition of Great Vessels:
It is a congenital disease in which the aorta and pulmonary arteries change their positions; the pulmonary artery comes from your left ventricle, and the aorta comes from your right ventricle. It causes cyanosis ( blue skin ) in the babies.
Underdeveloped Heart:
In DiGeorge syndrome, the heart is not developed correctly. This causes problems like decreased oxygenation and low blood pressure.

Problems with the Immune System:

DiGeorge syndrome decreases the immune system’s ability to fight infections. It affects the development of the thymus, which is essential for making white blood cells called lymphocytes. These lymphocytes help fight infections and keep you healthy. That is why, if you have DiGeorge syndrome, you are more at risk of getting infections.

Physical Findings:

Physical symptoms are:

Hearing loss
Vision loss
Muscle spasms due to decreased calcium. This hypocalcemia occurs due to the defective function of your parathyroid gland.
Feeding difficulties since birth
Respiratory infections
Cyanosis (blue skin)
Problems with the speech

Baby born with cyanosis - DiGeorge Syndrome — Baby born with cyanosis

Facial Features:

In DiGeorge syndrome, individuals often exhibit distinct facial features that can aid in diagnosis. These features may include:³

Babies with cleft lip and cleft palate- DiGeorge Syndrome — Babies with cleft lip and cleft palate

Cleft lip (an opening in the upper lip)
Cleft palate (the front and back parts of the palate are open)
Down-slanting palpebral fissures (the openings between the eyelids)
Hypertelorism (increased distance between the eyes)
Hooded eyelids
Long face shape
Low-set ears

Diagnosis DiGeorge Syndrome

Your doctor makes the diagnosis by taking a detailed history. In this history, the doctor may ask you about a family history of a genetic disease or any developmental abnormality, like cleft lip or palate and seizures. This is essential as family history is a risk factor for DiGeorge syndrome. After taking a proper history, your doctor may perform a complete physical examination to confirm the findings of the history.

Physical Examination:

Complete Cardiac Examination

Your doctor may conduct a complete heart examination to hear murmurs and confirm the congenital heart defects that may present in this condition.

Eye Examination

You may consider a complete eye examination to confirm whether the DiGeorge syndrome affects your vision.

Ear Examination

If you have DiGeorge syndrome, you should get your ears checked properly as early as possible because it can cause hearing loss.

Signs of Hypocalcemia

In DiGeorge syndrome, typical signs of hypocalcemia are positive because this syndrome affects the functioning of your parathyroid glands. As a result, parathyroid hormone levels decrease, leading to low calcium levels in the body.
Your doctor may check the following signs to see whether this syndrome affects your parathyroid glands.

Chvostek’s Sign: Your doctor checks this sign by gently tapping your cheek. If this sign is positive due to hypocalcemia, twitching of your cheek muscles is observed.
Trousseau Sign: Another sign of hypocalcemia is the trousseau sign. Your doctor can elicit this sign by inflating a blood pressure cuff on your arm and increasing the pressure to 20 mmHg above your normal systolic blood pressure. If the sign is positive, you will experience a carpopedal spasm characterized by the thumb adduction and flexion of the fingers and wrist.

Examination of Facial Features

DiGeorge presents with specific facial features, such as a cleft lip or palate, low-set ears, a small philtrum (the space between the upper lip and nose), or a relatively long face. Therefore, it is essential to examine facial features.

Psychiatric Evaluation

Psychiatric evaluation is vital because it can severely affect your brain. You may feel behavioral changes, anxiety, memory loss, or seizures.

Laboratory Tests:

Simple laboratory tests make it difficult to detect the microdeletions in your chromosomes in DiGeorge syndrome. Some specific tests can detect these microdeletions. However, these tests are relatively expensive.
These are:

Fluorescence in situ hybridization (FISH)
Single nucleotide polymorphism (SNP)
Polymerase chain reaction (PCR)

Some tests are done to confirm specific symptoms of this condition. These are:

Differential Blood Count

A complete blood count with the differentials shows a decreased level of T cells in your body. Low levels of T cells decrease your immunity and increase the risk of infection.

Echocardiogram

DiGeorge syndrome is associated with certain congenital heart diseases, and an echocardiogram helps to diagnose them.

Parathyroid Hormone Levels

DiGeorge syndrome affects the parathyroid glands, producing decreased parathyroid hormone (PTH). This hormone’s primary function is maintaining calcium levels; when it decreases, it causes hypocalcemia.

Serum Creatinine

In some cases, DiGeorge syndrome may affect normal renal function by increasing creatinine levels. Therefore, it is crucial to check serum creatinine and uric acid levels.

Chest X-ray

DiGeorge syndrome causes thymic hypoplasia (underdeveloped thymus). A chest X-ray helps see the underdeveloped thymus between the lungs and the sternum.

Immunoglobulin Levels

In DiGeorge syndrome, the level of immunoglobulins in your body decreases, leading to reduced immunity. It is essential to check immunoglobulin levels to avoid further complications.⁴

Treatment of DiGeorge Syndrome

This syndrome is mainly treated by boosting your immunity by different methods. These are:

Immunoglobulins:

Intravenous immunoglobins help boost immunity in DiGeorge syndrome, as a low level of T cells decreases immunity. Sometimes, a doctor may give antibiotic prophylaxis for infections associated with Digeorge syndrome.

Thymic or Hematopoietic Cell Transplantation:

DiGeorge syndrome causes thymic hypoplasia, which decreases the body’s T-cell count and affects natural immunity. You should consider thymic or hematopoietic cell transplantation, which has proven to be an effective treatment for DiGeorge syndrome.

Vaccines Against Infections:

Certain vaccines, such as MMR, oral polio, and Rota, should be administered prophylactically to treat infections like polio, measles, and diarrhea. Vaccines play an important role in boosting immunity against these infections.

Cardiac Surgery:

You should consult a cardiac surgeon to treat congenital heart defects like ventricular septal defect, narrowing of the aorta, and tetralogy of Fallot. Cardiac surgery ensures a better outcome in the case of DiGeorge syndrome.

Plastic Surgery:

Defects like cleft lip and cleft palate require plastic surgery. After plastic surgery, your face looks normal, and your speech difficulties improve.

Calcium & Vitamin D Supplements:

In DiGeorge syndrome, calcium levels decrease due to less parathyroid hormone production. To overcome calcium deficiency, you must take calcium supplements. Moreover, you must take Vitamin D supplements to increase your overall energy levels.

Treatment of Hearing Loss:

DiGeorge syndrome causes hearing loss. You can use a hearing aid to treat this.

Speech Therapy:

DiGeorge syndrome affects your everyday speech and how you speak to others. To improve your speech, consult a speech therapist. Speech therapy also improves your memory and behavior towards others.

Behavioral & Psychiatric Therapy:

Your doctor may advise you to take behavioral and psychiatric therapy because it helps to improve psychiatric symptoms like delusions, anxiety, or depression.

Genetic Counseling:

Genetic counseling plays a vital role in DiGeorge syndrome. You need to know about this disease if you have a baby with this syndrome and also if you want to conceive again. Better knowledge of the disease leads to its better management.⁵

Prognosis of DiGeorge Syndrome

The overall prognosis of DiGeorge syndrome is not good as it is a genetic disease, and there is no permanent cure for it. However, the severe form of DiGeorge syndrome occurs in less than 1% of patients. Even if you get a thymic and hematopoietic cell transplantation, the prognosis is poor. Most people live a relatively normal life with undiagnosed or milder forms of the disease.⁶

How can you prevent DiGeorge Syndrome?

DiGeorge syndrome is a genetic disease, and it is not entirely possible to prevent it. If you have a family history of this syndrome, consult a doctor before starting a family. If you get pregnant, go for genetic testing and neonatal screening. Early testing aids in diagnosing congenital cardiac defects.⁷

What is the Life Expectancy of a person with DiGeorge Syndrome?

Life expectancy depends on the severity of the disease. Early intervention and medical advancements have improved outcomes for many individuals. However, severe cases involving complex cardiac anomalies or profound immunodeficiency can reduce life expectancy. Despite these challenges, with proper management and supportive care, many individuals with DiGeorge syndrome can achieve a relatively normal life span, though they may require ongoing medical attention throughout their lives.⁸

When to see a doctor if my baby has DiGeorge Syndrome?

This syndrome remains undiagnosed in most of the patients. However, if your baby is born with cardiac defects, respiratory difficulties, or brain damage, you should consult a doctor as early as possible. Defects like cleft lip or palate should be treated by plastic surgery at almost 15 months of age.

Conclusion

In conclusion, DiGeorge syndrome is a disease caused by a microdeletion in chromosome 22q11.2. This microdeletion leads to underdevelopment of the thymus and affects natural immunity. Furthermore, It is associated with many other severe conditions, like congenital heart defects and brain diseases.
You can improve your immunity by transplanting thymic or hematopoietic cells, but you cannot treat this disease permanently. That is why its prognosis is poor. Always go for genetic testing if you have a family history of DiGeorge syndrome.

Refrences

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DiGeorge Syndrome: A Closer Look

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