What Is DiGeorge Syndrome?

Symptoms, Causes, Diagnosis, and Treatment

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Table of Contents

DiGeorge syndrome is a rare genetic disorder caused when a small part of chromosome 22 is missing. The symptoms of DiGeorge syndrome can vary both in severity and types. Some signs may be apparent at birth, such as cleft palate or a congenital heart defect, whereas others may only be noticed in later childhood.

Unlike other disorders associated with chromosome 22 (like Emanuel syndrome and trisomy 22), children born with DiGeorge syndrome may not have distinctive facial features at birth. As such, the disorder may only be diagnosed when there are obvious developmental delays, breathing problems, or heart problems occur later in life.

Although there is no cure for DiGeorge syndrome, there are various treatments that can help manage the symptoms. With treatment, life expectancy may be normal. Depending on the severity of the disorder, some children will be able to attend regular school and have children of their own.

Symptoms

The features of DiGeorge syndrome can vary enormously, even among family members diagnosed with the disorder. Common signs and symptoms include:

  • Congenital heart defects (such as heart murmurs, aortic regurgitation, ventricular septal defect, and tetralogy of Fallot)
  • Cyanosis (bluish skin due to poor blood circulation)
  • Cleft palate or lip
  • Orbital hypertelorism (wide-set eyes)
  • Palpebral fissures (narrowed eyelids)
  • Micrognathia (underdeveloped chin)
  • Low-set ears
  • Broad nose
  • Difficulty feeding and a failure to thrive
  • Delayed growth and developmental milestones
  • Short stature
  • Skeletal malformations
  • Learning disabilities (including ADHD or attention deficit-hyperactivity disorder and autism-like behaviors)
  • Language delays and speech problems (including nasally speech)
  • Low parathyroid function leading to acute hypocalcemia (low calcium)
  • Kidney dysfunction
  • Hearing loss
  • Seizures

Since DiGeorge syndrome commonly affects the thymus gland where immune cells (known as T-cells) are produced, people with the disorder often have poor immune function and are prone to frequent, severe infections. This also places them at greater risk of autoimmune disorders, including rheumatoid arthritis, Grave's disease, and autoimmune hemolytic anemia.

In terms of cognitive functioning, children with DiGeorge syndrome usually have below-normal IQs but can often attend regular school or special education classes.

As adults, people with DiGeorge are at an increased risk of psychiatric problems, with one in three experiencing at least one episode of psychosis and one in four meeting the clinical definition of schizophrenia.

Causes

DiGeorge syndrome, more accurately known as 22q11.2 deletion syndrome, is caused when portions of chromosome 22 (known as genes) are missing.

Everyone has two copies of chromosome 22, one inherited from each parent. With DiGeorge syndrome, anywhere from 30 to 40 genes will be missing.

The range and severity of symptoms are largely dependant on the types of genes deleted.

DiGeorge syndrome is classified as an autosomal dominant disorder, meaning that only one of the two chromosomes need to be affected for symptoms to develop. In around 90 percent of cases, the deletion will occur spontaneously during the early stages of fetal development. The remaining 10 percent will be inherited from the genetic material of one parent, usually the mother.

DiGeorge syndrome is rare, affecting only one of every 4,000 children. The chances of a person with DiGeorge syndrome having an affected child is 50 percent for each pregnancy. While some people are only moderately affected, nearly everyone with DiGeorge syndrome will require treatment from a variety of medical specialists.

Diagnosis

DiGeorge syndrome is typically diagnosed at birth or soon after birth based on the signs and symptoms of the disorder. Genetic testing can then be performed to confirm deletions on chromosome 22.

In some children, all of the classical features of DiGeorge syndrome will be seen at birth. In others, the presentation may be subtle and only be recognized when an impairment, either physical or development, become apparent.

Due to the variability of symptoms, genetic testing must be performed to confirm the diagnosis. This can be tricky since the pattern of deletions can often be so different, even between family members. The most reliable forms of genetic testing include:

  • Fluorescence in situ hybridization (FISH), in which a fluorescent agent binds to a chromosome to help identify its genetic sequence
  • Quantitative polymerase chain reaction (qPCR), which amplifies the number of chromosomes and evaluates their sequence using radioactive binding agents
  • Multiplex ligation-dependent probe amplification assay (MLPA), a newer variation of the PCR

The tests look at a specific portion of chromosome 22 called position 22q11.2. They only require a blood sample and are 95 percent accurate. Test results are usually returned within three to 14 days.

Other tests can be used for prenatal or postnatal screening, including array-comparative genomic hybridization (array-CGH), a test which can scan the entire genome of fetal cells and deliver results within five days.

Differential Diagnoses

For those with symptoms of DiGeorge syndrome but negative test results, additional tests may be performed to identify atypical deletions on chromosome 22. If none are found or the test results are inconclusive, a number of similar conditions may be explored, including:

  • CHARGE syndrome, a rare genetic disorder affecting multiple organs caused a mutation on chromosome 8
  • Opitz-G/BBB syndrome, a mutation of the X chromosome characterized by development delays, similar facial features, and problems affecting the larynx, esophagus, cleft, genitals, and heart
  • Isotretinoin exposure, in which fetal exposure to isotretinoin (such as those used for acne) can result in similar features to DiGeorge syndrome
  • Nonsyndromic anomalies, in which multiple, unrelated medical conditions occur without a unifying genetic cause

Treatment

There is no cure for DiGeorge syndrome. However, there are treatments available to address the various aspects of the disorder. The key is to identify and address each symptom under the care of a coordinating physician.

The care team may include specialists in maternal and fetal medicine, pediatrics, cardiothoracic surgery, learning disabilities, endocrinology, immunology, speech pathology, and audiology. A geneticist and genetic counselor are key members of the team.

Depending on the symptomatic presentation of the disease, various treatments may be prescribed for the following conditions:

  • Heart defects are most often treated with surgery soon after birth to repair the heart and correct blood circulation problems.
  • Cleft palates can usually be surgically repaired.
  • Parathyroid problems are typically treated with lifelong calcium and vitamin D supplements to correct nutritional deficiencies.
  • Mild thymus dysfunction can be usually be addressed by vaccinating children against the plethora of diseases that their immune systems will be able to fight. Antibiotics are often typically prescribed.
  • Severe thymus dysfunction, in which the impairment is severe or the thymus gland is completely missing, may require a thymus or bone marrow transplant.
  • Child development problems require a multidisciplinary approach, often including speech therapy, special education, occupational therapy, and developmental therapy.
  • Mental health issues may require therapy and pharmaceutical drugs to manage conditions like ADHD, depression, autism spectrum disorders, and schizophrenia.

The outlook of treatment can vary by the severity of the symptoms; there is not a single disease pathway or expected outcome.

However, many of the characteristic symptoms tend to resolve or become manageable over time with appropriate treatment. Others, particularly mental health issues, may develop and worsen over time—particularly those involving psychosis and schizophrenia. Early identification and intervention can greatly reduce the impact of these conditions.

Unlike some chromosomal deletions disorders, DiGeorge syndrome is not inherently associated with a shortened life span. Many people can live long, healthy lives and even have children.

Prevention

DiGeorge syndrome is a heterozygous chromosomal disorder, meaning that it is caused by the deletion of genes missing one only one of the two copies of chromosome 22. There is no known case of both copies being affected (a condition referred to as homozygosity).

The only way to prevent DiGeorge syndrome is by preventing the passing on of the chromosomal mutation to a baby.

Given that only around 10 percent of cases are directly associated with familial inheritance, this is more difficult than it seems.

As such, efforts are less focused on primary prevention (preventing disease before it occurs) and more on secondary prevention (preempting symptoms and complications once a disease is diagnosed). To this end, genetic testing is recommended for parents whose child has been positively diagnosed with DiGeorge syndrome.

Overall, more severe cardiac, parathyroid, and thymus-related diseases are seen in children for whom a relative has a 22q11.2 deletion.

Coping

Having a child with DiGeorge syndrome can be challenging. As a parent, you may need to manage multiple treatment issues with multiple providers while addressing the special needs of your child. Moreover, you would need to manage your own expectations for a disorder that has no clear course. This can cause enormous stress in parents who are often teetering between hope and setbacks.

To normalize DiGeorge syndrome in your life, start by educating yourself by working closely with your medical team and seeking quality medical information in clear and easy-to-understand language.

A good place to start is by reaching out to the non-profits agencies like the International 22q11.2 Foundation in Matawan, New Jersey or the 22q Family Foundation in Apto, California. In addition to providing practical advice, both organizations can refer to you to local or online support groups of parents, families, and individuals living with DiGeorge syndrome

There is even a growing number of specialty clinics dedicated to children with DiGeorge syndrome. They include the 22q Clinic at Phoenix Children's Hospital, the 22q Deletion Clinic at the SickKids Hospital in Toronto, and the 22q Children's Clinic at Massachusetts General Hospital in Boston.

A Word From Verywell

If your baby has been diagnosed with DiGeorge syndrome, try not to expect the worst. Doing so can leave you in a constant state of anxiety, anticipating whether a new symptom is developing or not.

If you are unable to cope, try not to suffer in silence. Instead, ask your doctor for a referral to a therapist experienced in working with families with disabilities. In some cases, one-on-one counseling and potentially prescription medications can help you overcome feelings of hopeless, depression, and anxiety.

You may benefit from mind-body therapies aimed at reducing stress, including meditation, guided imagery, mindful breathing, and progressive muscle relaxation (PMR). By taking care of yourself, you will be better able to take care of others.

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Article Sources

  • Fung, W.; Butcher, N.; Costain, G. et al. Practical guidelines for managing adults with 22q11.2 deletion syndrome. Genet Med. 2015 Aug;17(8):599-609. DOI: 10.1038/gim.2014.175

  • McDonald-McGinn, D. and Sullivan, K. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine. 2011 Jan;90(1):1-18. DOI: 10.1097/MD.0b013e3182060469