DiGeorge and/or Velocardiofacial Syndrome
What is DiGeorge syndrome?
A syndrome is a disease or disorder that has more than one identifying feature or symptom that has been noted to repeat over and over in different patients. With DiGeorge syndrome (named after the physician who recognized this frequently occurring grouping of symptoms) the identifying features are: a few specific cardiac malformations, immune deficiencies and endocrine disorders. The most common heart anomalies seen are: tetrology of Fallot, interrupted aortic arch, truncus arteriosus, ventricular septal defect, and vascular rings. The most common immune disorder is an underdeveloped or absent thymus. The thymus gland is located behind the breastbone and is responsible for the maturation or maturing of T-cells to fight infections. Finally, the most common endocrine problem is an underactive parathyroid gland. The four parathyroid glands are located adjacent to the thyroid gland in the neck and 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 and is applied only to those patients for whom the triad of symptoms applies (ie: heart disorder, thymus/immune disorder and parathyroid or calcium problems) and the genetic analysis is negative for a mistake on gene 22q11.
What is Velocardiofacial syndrome?
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 percent 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. These children often have a congenital heart defect. A large percentage will have a cleft lip and/or palate or a high arched palate. Many of these children will have hearing loss and generally a lower IQ (70 to 90 range). A large number will have problems with low calcium levels in their blood. Children with 22q11 have a typical facial appearance that includes small, low-set ears with squared upper ear, hooded eyelids, cleft lip and/or palate, asymmetric crying facies, small mouth, chin and side areas of the nose tip. Learning problems, particularly with speech and language are common. Problems with the immune system can vary widely from no problem to a problem with frequent infections to severe issues that may require bone marrow transplant.
VCFS also 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, it is known that only about 10 to 15 percent of new cases have been inherited. In most cases, neither parent is a carrier 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).
Prenatal Diagnosis of 22q11:
Prenatal diagnosis 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 is performed and the fluid sent for fluorescence in situ hybridization, or FISH. The physician must specifically request that the laboratory perform the test for 22q11 deletion. It is not a test done routinely on amniotic fluid. Your obstetrician will most likely refer you to a specialist that handles high-risk pregnancies. These doctors are called perinatologists. A thorough examination with a targeted ultrasound will be done to look at all systems of the baby for associated anomalies.
Even if the FISH is negative for 22q11, the baby may have the diagnosis of DiGeorge or VCFS. About 10 percent will 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 these patients who are found to 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.
How does 22q11 affect my baby?
Approximately 90 percent 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 or VCFS or more appropriately referred to as 22q11. One thing that is not understood is how these children with the same missing piece of chromosome will 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 severely each disorder will be.
This is an autosomal dominant disorder. This means only one parent needs to have the gene for VCFS in order to pass it along to their children.The offspring of a carrier/affected parent has a 50/50 chance of inheriting the disorder. Therefore, your child will have a 50/50 chance themselves of passing on 22q11 to their offspring. 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.
How does 22q11 affect my pregnancy?
When a prenatal diagnosis of 22q11 is made, it will be recommended that each parent have a consultation with a geneticist or genetic counselor. The geneticist or genetic counselor 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 gone undiagnosed. Should either of you be found to have the deletion, the next step would be to evaluate others in the family to determine if it exists in siblings, grandparents, etc. Family members capable of having children who are found to have 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 1 in 3,000.
The prenatal diagnosis does not usually affect the pregnancy itself. 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 and the potential issues he or she faces. The facility at which the baby is cared for should be familiar with the diagnosis and potential complications that these children may face.Your regular obstetrician may refer you to a doctor who cares for high-risk pregnancies. These doctors are called perinatologist. By knowing before your baby is born, you will have the time to get information about this diagnosis and begin to make decisions about care options before the baby arrives.
How is 22q11 treated?
Treatment is dependent on the features of the syndrome. The heart disorder will be evaluated and treated by a cardiologist and cardiovascular surgery. Clefting of the lip and/or palate will be initially evaluated and eventually corrected by plastic/craniofacial surgeons. The cleft palate team will assist with feeding issues. Speech and language therapists will help with the issues related to their area. Ear, nose and throat and audiology specialists can provide services related to hearing loss. Endocrinologists can assist with treatment of the low calcium levels. An immunologist can assist in determining the degree of immune dysfunction. Geneticists will provide an overview of the diagnosis. 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.
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.
The heart disorder is the main concern initially. After birth, an echocardiogram or ultrasound of the heart will be done to assess the heart defect and determine the diagnosis. Results of these tests and observation of how the 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 for some time, until he or she has been evaluated and/or until surgery has been done.
Some special lines may be placed during this time of evaluation. These can include two IV lines in the baby's umbilical cord. The umbilical cord normally has two arteries and one vein. A small, thin tube or catheter will be put into the one vein to provide nutrition. This is called an umbilical venous catheter (UVC). A second catheter will be placed in one of the arteries. This is called an umbilical artery catheter. Fluids and medications can be given, blood pressure can be monitored and blood can be taken for lab work through the UAC. An IV also may be placed in the baby's hand, arm, scalp, lower leg or foot.
Your baby will require frequent blood draws for lab work to monitor oxygenation, electrolytes, calcium levels, blood count and other things. The baby also may be on a variety of medications that can include antibiotics to fight infection, pain medication and sedation to keep him or her quiet.
Because the baby will not eat until after he or she has been evaluated, special nourishment is given 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 he or she is 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 the 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. Evaluation of the clefting will be done by the craniofacial team and plastic surgeon. Once the baby is allowed to eat, the clefting may cause feeding problems. The cleft team can help with techniques to make it a more successful and enjoyable experience.
Will I be able to help care for my baby after surgery?
Yes. If your baby needs some type of surgery you will be encouraged to continue to participate in 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 assist in answering 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. You can bring in pictures, small toys, booties, and blankets for your baby while he or she is in the NICU.
When can my baby go home?
Your baby can go home when he or she is eating and tolerating enough food to maintain and allow them to grow and gain weight. There is no typical baby with 22q11. Each baby is very individual as to the extent of involvement of each body system. The length of stay will vary depending on the need for surgery. It will especially be affected by the type of heart defect and the repair required. The surgery will be scheduled dependent on the stability of the baby. Since these babies can be more prone to infections, if they should develop an infection while in the hospital this will delay other treatments especially surgery. The calcium level and its stability is another potential complication to the treatment plan for any surgical interventions.
What is the long-term prognosis for 22q11?
Long-term prognosis for most babies born with 22q11 is a long life with some health issues that require long-term followup. There are a small minority of children with this syndrome that will have such severe involvement, especially of the heart and immune system that they will not survive the first year of life. However, the majority of these children will have a treatable heart condition and the immune system disorders will not be significant enough to interfere with survival. Most survive into adulthood with normal growth and only slightly lowered intelligence. They will need long-term followup by a variety of specialists to manage their health issues.
Learn more about services at Children's Hospital of Wisconsin:
Herma Heart Center
Immunodeficiency Program
Endocrine Clinic
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