A syndrome is a disease or disorder that has more than one identifying feature or symptom that occurs over and over in different patients.
DiGeorge syndrome was named after the physician who recognized this frequently occurring grouping of symptoms.
The identifying features of DiGeorge syndrome are:
The most common heart anomalies seen are:
The most common immune disorder is an underdeveloped or absent thymus. The thymus gland is located behind the breastbone and helps our T-cells, which fight infection, to mature.
The most common endocrine problem is an underactive parathyroid gland. The four parathyroid glands are located adjacent to the thyroid gland in the neck. They regulate the calcium levels in the blood.
An underactive parathyroid will result in hypocalcemia (low blood levels of calcium), which can result in seizures.
The diagnosis name of DiGeorge is used less frequently now than in the past. It is applied only to those patients who have the entire triad of symptoms (i.e.: heart disorder, thymus/immune disorder and parathyroid or calcium problems) and genetic testing is negative for a mistake on gene 22q11.
Velocardiofacial syndrome, or VCFS, is a related disorder with a much broader spectrum of symptoms. The name velocardiofacial comes from "velum" referring to the palate, "cardia" referring to the heart and "facies" referring to the face.
VCFS has also been referred to as Shprintzen syndrome after the physician who described the collection of symptoms. At about the same time as Shprintzen, another physician in Japan named the syndrome “conotruncal anomaly face syndrome.”
It has been discovered that approximately 90% of the children with this combination of symptoms (referred to by any of the above names: DiGeorge, Shprintzen, conotruncal anomaly face syndrome or VCFS) are missing a small portion of genetic material on chromosome 22. This condition is referred to as 22q11.
There are other similarities between children with this condition, including:
VCFS is an autosomal dominant disorder. This means that only one parent needs to have the gene in order to pass it along to their children. When one parent has VCFS (and thus the gene for it), the chance of passing it on to their offspring is 1 in 2. However, only about 10-15% of new cases have been inherited. In most cases, neither parent carries the gene and the cause is unknown.
There has been an association of these features with maternal diabetes, fetal alcohol syndrome and prenatal exposure to Accutane (a medication for cystic acne). We also know that this area of chromosome 22 is prone to loss (or deletion).
VCFS may be suspected if a heart defect and cleft palate are observed on routine ultrasound. To determine before birth if there is a chromosomal abnormality, an amniocentesis must be performed and the fluid sent for a fluorescence in situ hybridization (FISH) study.
Your doctor must specifically request that the laboratory perform the test for 22q11 deletion. It is not a routine amniotic fluid test. Your doctor likely will refer you to a maternal-fetal medicine specialist (a doctor that handles high-risk pregnancies). Your maternal-fetal medicine specialist will perform a thorough examination with a targeted ultrasound to look at all systems of your baby for associated anomalies.
Even if the FISH study is negative for 22q11, your baby may be diagnosed with DiGeorge or VCFS. About 10% of all babies with these syndromes do not have the deletion, but will have symptoms that put them into classification for this diagnosis. A small percentage may have a deletion on chromosome 10. This can be detected with a different FISH test. However, for some, the FISH test will be normal.
The most accurate term to use when referring to the diagnosis for patients who have a deletion is the genetic term 22q11, as this is the most descriptive. There is much confusion, even in the medical community, regarding classification of this collection of symptoms.
Approximately 90% of infants with features of DiGeorge/VCFS are missing a small part of their chromosome 22 at the q11 region. Chromosomes are threadlike structures found in every cell of the body. Normally a cell contains 46 chromosomes – 23 from each parent. Each chromosome contains hundreds of genes.
Genes are found in every cell and are there to tell the cell what to do. The result of the missing genes is a genetic disorder known as velocardiofacial syndrome, VCFS or more appropriately, 22q11.
One thing that is not understood is how these children with the same missing piece of chromosome have such varied symptoms. Scientists are continuing to study chromosomes and genes in order to get a better understanding of their complexity.
There is no typical child with 22q11. Each child will vary in what disorders they have, which systems will be affected and how severe each disorder will be.
There is a wide spectrum of potential disorders associated with VCFS that can affect the child to varying degrees. Not every child will have every feature and the severity will vary greatly from child to child.
If your child is diagnosed before birth with 22q11, we recommend that each parent talk with a geneticist or genetic counselor. This person may recommend that each of you have a blood test to evaluate if either of you may also have 22q11 deletion that has been mild and undiagnosed.
Should either of you have the deletion, the next step would be to evaluate others in the family to determine if it exists in siblings, grandparents or other blood relatives. Family members capable of having children with this deletion will be counseled regarding the risk of passing it on to their offspring. If neither of you are found to have the deletion, the chance of having another child with 22q11 is the same as that in the general population, which is approximately one in 3,000.
The prenatal diagnosis does not usually affect the pregnancy. It may be preferable for the delivery to occur at a center with all the specialists available to assist with diagnosis and treatment of your child.
The facility at which your baby is cared for should be familiar with the diagnosis and potential complications your child may face.
By knowing about the diagnosis before your baby is born, you will have the time to get information about this diagnosis and make decisions about care options before your baby arrives.
Treatment of this disorder is specific to the symptoms that your child exhibits. There is no set plan of care, as each child presents differently. However, a team is necessary for full evaluation.
A number of specialists will be involved in your baby’s care:
The initial care of your baby after delivery will vary depending on whether there is a heart defect or not. If there is a heart defect, the care may look something like what is described below.
At first, the heart disorder is the main concern. After birth, we will perform an echocardiogram or ultrasound of the heart to assess the heart defect and determine the diagnosis. Results of these tests and observation of how your baby is doing will help determine a treatment plan.
If surgery is necessary, a pediatric cardiothoracic surgeon will discuss that treatment with you. Your baby will not be able to eat until they have been evaluated and/or until surgery has been done.
Doctors may place some special lines during the evaluation period. These can include two IV lines in the baby's umbilical cord.
Your baby will require frequent blood draws for lab work to monitor oxygenation, electrolytes, calcium levels, blood count and other things.
Your baby also may be on a variety of medications that can include:
Because your baby will not eat until after they have been evaluated. However, we will provide special nourishment through the UVC. Total parenteral nutrition is an IV solution that contains protein, fats, sugar, vitamins and minerals. This will supply your baby with all his or her nutritional requirements until they are able to take food by mouth. TPN has two components. One solution, called hyperalimentation, is yellow and contains everything but the fats. The other solution is white and is called lipids. This is the fats component.
The hypocalcemia may pose a challenge in care. For some babies, it is difficult to keep the calcium level at an acceptable range. If the calcium level is too low, the baby is at risk for seizures. Initially, calcium supplement, if needed, is given in the IV solution. The calcium levels are evaluated with a blood sample. Eventually, calcium supplements along with vitamin D are usually given by mouth.
Another issue that can cause problems initially is if there is a cleft lip and/or palate. Our craniofacial team and plastic surgeon will evaluate the clefting. Once your baby is allowed to eat, the clefting may cause feeding problems. Our cleft team can help make feeding a more successful and enjoyable experience.
Yes. If your baby needs some type of surgery, we will encourage you to continue to participate in care and learn how to care for your baby. Ask your infant's nurse about ways to interact with and care for your baby.
If you had planned to breastfeed, you can begin to pump your breasts and freeze the breast milk while you are still in the hospital. A lactation consultant can answer your questions. Your milk will be frozen and stored in the Neonatal Intensive Care Unit until your baby is ready for it. The NICU has breast pumps and private rooms available to you when you are visiting.
Your baby can go home when they are eating and tolerating enough food to grow and gain weight. There is no typical baby with 22q11. Each baby is very individual as it relates to the extent of involvement of each body system.
Your baby’s length of stay will vary depending on whether or not they need surgery. Length of stay will be especially affected by the type of heart defect and the repair required.
Surgery will be scheduled depending on your baby’s stability. Since babies with this syndrome can be more prone to infections, if your baby develops an infection while in the hospital, treatments will be delayed, especially surgery. Calcium level and stability is another potential complication to the treatment plan and any surgical interventions.
Long-term prognosis for most babies born with 22q11 is a long life with some health issues that require long-term care. A small minority of children with this syndrome have such severe involvement, especially of the heart and immune system, they will not survive the first year of life. However, the majority of children with 22q11 will have a treatable heart condition, and the immune system disorders will not be fatal.
Most survive into adulthood with normal growth and only slightly lowered intelligence. They will need long-term follow-up by a variety of specialists to manage their health issues.
