DiGeorge syndrome is a rare genetic disorder that affects an estimated 1 in 4,000 to 1 in 6,000 people worldwide. It is part of a group of syndromes collectively known as 22q11.2 deletion syndrome. These disorders can cause a range of behavioural, physical, and developmental symptoms.
The group of syndromes referred to as 22q11.2 deletion syndrome are Conotruncal anomaly face (CTAF) syndrome, Velocardiofacial syndrome, and DiGeorge syndrome. These all have common overlapping features that result from the deletion of a part of chromosome 22 called the DGS critical region.1
Keep reading to discover the features of DiGeorge syndrome, how it is diagnosed, treatment options, and its progression.
DiGeorge Syndrome, also known as 22q11.2 deletion syndrome, is a genetic disorder resulting from a small deletion of a region of DNA on chromosome 22. In this article, the symptoms, diagnosis, and treatment options for DiGeorge Syndrome will be explored, as well as information on its prevalence and potential complications. Additionally, this article will discuss how DiGeorge Syndrome can impact a person's daily life and offer advice for managing the condition.
Causes of DiGeorge syndrome
DiGeorgue syndrome most commonly results from the deletion of part of chromosome 22, during the development of an embryo. Even though only a small part of the chromosome is deleted, implications may include numerous abnormalities in the embryo during development. The size of the deletion varies and determines the severity of the condition
Signs and symptoms of DiGeorge syndrome
The most common and serious manifestation of this syndrome is heart abnormalities. Since the deleted region of the chromosome contains genetic material responsible for the development of the face and chest, the signs and symptoms are related to the structures within the face, neck, chest, and associated areas.
Congenital heart defects like Ventricular Septal Defect and Tetralogy of Fallot are common in people with DiGeorge syndrome. The heart defects depending on their severity may be discovered at birth or when the individual is older in age.
Distinctive facial features
Characteristic facial features of this condition include a long face, a small jaw, a broad nasal bridge, and narrow palpebral fissures. These features are more noticeable as the child develops with age and are easier to recognise in Caucasian children. Other features may include a small head and a dimpled nose.
Low blood calcium can be caused by parathyroid hormone deficiency. Parathyroid hormone is produced by the parathyroid gland in humans and controls the amount of calcium in the blood. A low calcium level in the blood may cause seizures.
Behavioral and psychiatric disorders
Individuals with DiGeorge syndrome may develop behavioral and psychiatric disorders. Some communication disorders that are common in these children include autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). There is also an increased risk of early-onset Parkinson's disease.2
Feeding and speech difficulties
Abnormalities of the palate, such as cleft lip and cleft palate, may lead to feeding and speech difficulties. These conditions often require surgical correction and speech therapy.
Repeated infections are a common feature of DiGeorge syndrome and an important cause of mortality in individuals with the condition. These individuals are more prone to fungal, bacterial, and viral infections due to their underdeveloped thymus, which is an organ that plays a vital role in the body's ability to fight infections. Asthma is another condition that is commonly present in these individuals.
Diagnosis of DiGeorge syndrome
A combination of laboratory tests and clinical exams is employed to diagnose DiGeorge syndrome. Clinicians often suspect the syndrome when the patient presents with various symptoms or manifestations.
- Prenatal testing: These are tests that can be carried out during a pregnancy to determine if a fetus has the syndrome. It is often considered if there is a possibility of the fetus having the disease, like the existence of a sibling or parent with DiGeorge syndrome.
- Laboratory tests: Blood tests include complete blood counts and hormonal assays
- Imaging studies: These include tests like Magnetic resonance imaging, Computed tomography (CT) scans, and echocardiography to visualise abnormalities of the heart and other organs
Management and treatment for DiGeorge syndrome
Since the symptoms of DiGeorge syndrome are a spectrum and vary from patient to patient, treatment is organ-based and can vary.
- Immunologic therapy: Form of treatment to stimulate, enhance and modulate the immune system by using substances to boost an individual’s immune response.
- Surgery: A lot of patients with DiGeorge syndrome suffer from heart defects or facial abnormalities like cleft lip and cleft palate which require surgical intervention to repair them.
- Mineral supplementation and hormone replacement therapy: Calcium and parathyroid hormone replacement may be required in cases where the patient has underdeveloped parathyroid glands.
- Psychiatric and educational therapy: Some psychiatric support might be required for patients with psychiatric disorders and learning support for those with developmental delays or learning disabilities
- Patient education: Genetic counselling is an important part of therapy for DiGeorge syndrome. Parents need to be educated about the complications of the condition and resources to help with those complications as needed. Due to the rare nature of the disease, families need to have access to resources and relevant organisations that offer support
Factors such as a previous child with the condition or a parent with the condition increase the chances of a child being born with the syndrome.
Individuals with DiGeorge syndrome have an increased risk of developing an autoimmune disease such as rheumatoid arthritis, lupus, and psoriasis.3 The thymus, an organ in the body that produces T-cells, is underdeveloped in some patients with DiGeorge syndrome. This results in impaired T-cell production, which is an important component of the immune system’s ability to help fight infection. Despite the benefits of T-cells for the immune response, they also have the ability to attack the body itself, and this is commonly prevented by the thymus. An underdeveloped thymus therefore does not have the ability to efficiently weed out cells that could attack the body and this may increase the chance of developing autoimmune diseases. Early diagnosis and management of the disorder are essential for individuals with DiGeorge syndrome to live healthy, and fulfilling lives.
How can I prevent DiGeorge syndrome?
Because 90% of cases of DiGeorge syndrome mutations occur sporadically with only 10% resulting from an inherited mutation, it is not preventable. However, individuals with symptoms of the disorder should seek medical attention. Genetic counseling and testing can help you understand the risk of having a child with DiGeorge syndrome and help you plan for appropriate treatment and care
How common is DiGeorge syndrome?
DiGeorge syndrome is estimated to occur in 13 per 100,000 infants4. It is less common than other genetic mutations like Down syndrome
When should I see a doctor?
If you or your child have any of the symptoms listed above, it is wise to consult your doctor for an accurate diagnosis
DiGeorge Syndrome is part of a group of syndromes known as 22q11.2 deletion syndrome. It is a genetic disorder caused by the deletion of a section of chromosome 22. The genes in the affected region play a part in the development of organs like the heart, and parathyroid gland, as well as several facial structures and the palate. Symptoms can vary in severity and how they manifest depending on how much genetic material is lost. Symptoms may include congenital heart defects, psychiatric disorders, learning difficulties, abnormal facial features, and speech difficulties. Treatment is centred around managing symptoms and complications with surgery and hormone replacement. Patients may also benefit from psychiatric and educational therapy, as well as genetic counselling.
- Gao W, Higaki T, Eguchi-Ishimae M, Iwabuki H, Wu Z, Yamamoto E, et al. DGCR6 at the proximal part of the DiGeorge critical region is involved in conotruncal heart defects. Hum Genome Var [Internet]. 2015 Feb 12 [cited 2023 Apr 28];2(1):1–7. Available from: https://www.nature.com/articles/hgv20154
- Butcher NJ, Kiehl TR, Hazrati LN, Chow EWC, Rogaeva E, Lang AE, et al. Association between early-onset parkinson disease and 22q11. 2 deletion syndrome. JAMA Neurol [Internet]. 2013 Nov [cited 2023 Apr 28];70(11):1359–66. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464823/
- Tison BE, Nicholas SK, Abramson SL, Hanson IC, Paul ME, Seeborg FO, et al. Autoimmunity in a cohort of 130 pediatric patients with partial DiGeorge syndrome. Journal of Allergy and Clinical Immunology [Internet]. 2011 Nov 1 [cited 2023 Apr 28];128(5):1115-1117.e3. Available from: https://www.sciencedirect.com/science/article/pii/S0091674911010657
- A population study of chromosome 22q11 deletions in infancy. [Internet]. Read by QxMD. [cited 2023 Apr 28]. Available from: https://read.qxmd.com/read/9875047/a-population-study-of-chromosome-22q11-deletions-in-infancy