The birth of a child is a momentous occasion, but when a baby is born with complex medical issues, it can bring a wave of uncertainty and concern for parents. One of the conditions that can present this challenge is 22q11.2 Deletion Syndrome. You may also know this condition by one of its older names, such as DiGeorge syndrome or Velocardiofacial syndrome (VCFS). This is a complex condition caused by a small missing piece of a chromosome, which can lead to a wide and variable range of health and developmental issues. While the diagnosis is serious and presents lifelong challenges, it is the first and most critical step toward providing the comprehensive, team-based medical care that can help a child navigate their unique journey and thrive.

DiGeorge syndrome is a congenital disorder caused by a microdeletion on chromosome 22. To better understand what this means, it is helpful to think of our genetic code as a multi-volume encyclopedia of instruction manuals for building a human body. Each of our 23 pairs of chromosomes is a single volume.

• In DiGeorge Syndrome, it is as if a small, but very important, paragraph containing several key instructions has been accidentally erased from the middle of the manual for Chromosome 22.
• The specific address of this missing paragraph is “q11.2”, which simply refers to its location on the long (q) arm of the chromosome.

Because this deleted segment contains approximately 30 to 40 different genes, its absence can disrupt the normal development of several different body systems. This is why the condition can cause such a wide array of seemingly unrelated problems. In recent years, doctors have moved away from using older names like DiGeorge syndrome and VCFS, preferring the more precise genetic name 22q11.2 Deletion Syndrome (22q11.2DS), as it accurately describes the underlying genetic cause for all individuals on this spectrum.

The effects of DiGeorge syndrome are incredibly variable. Some individuals may have very severe medical problems, such as complex heart defects and a non-functional immune system, while others may have much milder features, such as learning disabilities and subtle palate problems, and may not be diagnosed until later in life.

DiGeorge syndrome is caused by the physical loss (deletion) of a specific segment of genetic material from chromosome 22 at the q11.2 location. This is not a mutation in a single gene, but a larger-scale chromosomal error where a whole block of genes is missing.

This deletion disrupts the normal process of embryonic development, particularly the formation of structures that arise from the pharyngeal arches in a developing fetus. Research has identified that the loss of one specific gene within this region, called TBX1, is responsible for many of the most common features of the syndrome, including the characteristic heart defects, palate abnormalities, and low calcium levels. The loss of other genes in the deleted segment contributes to the risk of developmental delays and other health issues.

Many parents are surprised to learn the condition wasn’t inherited. I always explain that most cases happen by chance during early fetal development, there’s nothing they did wrong.

A diagnosis of a chromosomal condition often leads parents to ask, “How did this happen?” It is vital to understand that for this syndrome, the genetic error is almost always a random event.

A Sporadic, de novo Event

In approximately 90% of all cases, DiGeorge syndrome is sporadic, or de novo. This means the deletion occurred as a brand-new, random accident during the formation of either the egg or the sperm cell in a healthy parent, or it occurred very early in fetal development. The parents have normal chromosomes, and there is absolutely nothing they did or did not do to cause this to happen. When a deletion is de novo, the risk of the parents having another child with the same syndrome is very low (less than 1%).

Inherited Form

In about 10% of cases, the deletion is inherited from a parent who also has the syndrome (though they may have a very mild, undiagnosed case).

• The condition is inherited in an autosomal dominant pattern. This means an individual with the deletion has a 50% chance of passing it on to each of their children.
• This is why it is recommended that parents of a newly diagnosed child undergo genetic testing themselves. This helps provide accurate genetic counseling about risks for future pregnancies.

When I diagnose a child with DiGeorge, I always suggest testing the parents, even if they’re healthy, because sometimes the deletion is silently passed down.

Symptoms of DiGeorge syndrome are extensive and highly variable. The most common features are often remembered by the mnemonic CATCH-22, although it is crucial to remember that very few individuals will have all of these features.

The CATCH-22 acronym stands for:

• Cardiac Defects: Congenital heart defects are present in approximately 75% of individuals with DiGeorge syndrome and are often the first sign that leads to a diagnosis.  Common defects include Tetralogy of Fallot, truncus arteriosus, ventricular septal defect (VSD), and interrupted aortic arch.
• Abnormal Facies: Many children share a subtle but recognizable set of facial features. These can include small, low-set ears; hooded or heavy eyelids; a short or flattened philtrum (the groove between the nose and upper lip); and a small mouth and chin.
• Thymic Hypoplasia/Aplasia: The thymus is a gland located behind the breastbone that is critical for the development of T-cells, a vital part of the immune system. In DiGeorge syndrome, the thymus is often underdeveloped (hypoplasia) or, in rare cases, completely absent (aplasia). This results in immunodeficiency, making the child highly susceptible to recurrent infections.
• Cleft Palate: Palate abnormalities are very common. This can be an obvious opening in the roof of the mouth (cleft palate) or a more subtle problem called a submucous cleft palate or velopharyngeal insufficiency, which can cause speech to sound nasal and can lead to feeding difficulties.
• Hypocalcemia/Hypoparathyroidism: The parathyroid glands, which regulate calcium levels in the blood, are often underdeveloped. This leads to low blood calcium levels (hypocalcemia), especially in neonatal period, which can trigger seizures.

Other Common Signs and Symptoms

Beyond the CATCH-22 features, there is a wide range of other issues that are common in individuals with DiGeorge syndrome.

• Feeding and Gastrointestinal Issues: Difficulty feeding in infancy is very common due to low muscle tone and potential palate problems. Chronic constipation is also a frequent issue.
• Developmental and Learning Challenges: Most individuals will experience some degree of developmental delay and learning disability. Delays in reaching motor milestones and significant speech and language delays are particularly common.
• Psychiatric and Behavioral Issues: There is a significantly increased risk for mental health conditions later in life, particularly anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), and, in adulthood, a much higher risk of developing schizophrenia.
• Other Physical Issues: Kidney abnormalities, hearing loss, and skeletal issues like scoliosis can also occur.

One of the biggest red flags I look for is a combination of cardiac and immune issues. If a child has both a heart defect and frequent infections, I always consider DiGeorge a possibility.

A diagnosis of DiGeorge syndrome may be suspected prenatally if a routine ultrasound shows a major heart defect or other physical markers. After birth, it is often suspected in a newborn who has a congenital heart defect, hypocalcemic seizures, or the characteristic facial features.
The diagnostic process involves several steps:

1. Clinical Evaluation: A thorough physical examination by a pediatrician or clinical geneticist to look for the combination of features associated with the syndrome.
2. Initial Workup: If the syndrome is suspected, initial tests will include an echocardiogram to evaluate the heart and blood tests to check calcium levels.
3. Definitive Genetic Testing: The diagnosis is confirmed with a genetic test using a blood sample.
   • Fluorescence In Situ Hybridization (FISH): This was the classic test. It uses a specific fluorescent DNA probe that is designed to bind to the 22q11.2 region. If the region is missing, the probe has nowhere to attach, and the result is positive for a deletion.
   • Chromosomal Microarray: This is now the standard and more comprehensive test. It can not only detect the 22q11.2 deletion but can also determine its exact size and check all other chromosomes for any additional abnormalities.

I recommend testing for DiGeorge whenever a child has multiple unexplained anomalies, especially heart defects paired with developmental delays or immune problems.

There is no cure for DiGeorge Syndrome, but symptoms can be managed with a team-based approach involving pediatricians, cardiologists, immunologists, endocrinologists, and speech or developmental therapists.

The care team for a child with DiGeorge syndrome is large and may include:

• A Pediatrician and a Clinical Geneticist to oversee care.
• A Cardiologist to manage heart defects.
• An Immunologist to manage the immunodeficiency.
• An Endocrinologist to manage hypocalcemia.
• An ENT specialist and a Plastic Surgeon for palate issues.
• Numerous therapists, including Speech, Physical, and Occupational therapists.
• A Developmental Pediatrician and a Psychologist/Psychiatrist for developmental and mental health support.

Key management strategies include:

• Cardiac Care: Many children will require open-heart surgery in infancy to repair congenital heart defects. Lifelong follow-up with a cardiologist is essential.
• Immune System Management: This involves careful monitoring of immune function, prompt treatment of any infections, and a carefully considered vaccination schedule. In children with severe immunodeficiency, live virus vaccines may need to be avoided.
• Calcium Management: Lifelong supplementation with calcium and vitamin D is often required to manage hypoparathyroidism.
• Palate and Speech Therapy: Surgery may be needed to repair a cleft palate or improve velopharyngeal function. Intensive speech therapy is almost always necessary to help with language development.
• Developmental Support: Early intervention is the cornerstone of helping a child reach their potential. This includes starting physical, occupational, and speech therapy as early as possible. Most children will require an individualized education plan (IEP) and support throughout their schooling.
• Mental Health Care: Regular screening and support for anxiety, ADHD, and other psychiatric conditions is a critical part of lifelong care, especially during adolescence and adulthood.

Families often feel overwhelmed, but I emphasize that early coordination with specialists can make a huge difference. Many kids with DiGeorge go on to attend school and live fulfilling lives with the right support.

DiGeorge syndrome is a complex chromosomal disorder with an incredibly wide range of potential health and developmental impacts. For families, the journey is one of navigating a complex medical system and advocating for the needs of their child. While the challenges are significant and lifelong, it is important to remember that it is almost always a random event and not the fault of the parents. A proactive and coordinated multidisciplinary team approach can successfully manage complex medical needs. What I always tell parents is this: while DiGeorge comes with challenges, your child’s potential is not defined by a diagnosis. With love, structure, and the right care team, they can truly thrive.

1. National Institutes of Health, Genetic and Rare Diseases Information Center (GARD). (2024). 22q11.2 deletion syndrome. Retrieved from https://rarediseases.info.nih.gov/diseases/5902/22q112-deletion-syndrome
2. The 22q Family Foundation. (n.d.). What is 22q? Retrieved from https://www.22q.org/what-is-22q/
3. The Children’s Hospital of Philadelphia. (n.d.). 22q11.2 Deletion Syndrome. Retrieved from https://www.chop.edu/conditions-diseases/22q112-deletion-syndrome