Genes carry information about heredity and are responsible for all the physical characteristics of a human being. Genetic disorders can cause minor or major problems because one or more genes are defective or absent.
Chromosomal disorders are a type of genetic disorder in which an entire chromosome or part of it is missing, changed, or duplicated. 22q11.2 deletion syndrome is a chromosomal disorder in which a small part of chromosome 22 is missing (deleted). Each chromosome holds hundreds of genes, and the manifestations of 22q11.2 deletion syndrome depend on which genes have been lost. It commonly causes problems with the heart, palate, ears, immune system, spine, brain, and kidneys.
What Is DiGeorge Syndrome?
DiGeorge syndrome is one of the manifestations of 22q11.2 deletion. The lost genes in this condition chiefly affect the heart, brain, mouth, immunity, and hormonal system. The common DiGeorge syndrome symptoms are:
Congenital heart disease. Defects of the heart are present at birth. Some of these congenital heart diseases are fatal in early childhood if not corrected by surgery.
Problems with development and behavior. These children are often slow to learn skills like walking and speaking. They may also have learning disabilities, autism, or attention deficit hyperactivity disorder (ADHD).
Hormonal disorders. The parathyroid glands are poorly developed, causing a deficiency of parathormone. This disturbs calcium control, and the child may have tremors or seizures (fits).
Mouth and feeding issues. A cleft palate is a defect in the roof of the mouth opening into the nose. A cleft lip is a defect in the upper lip (hare lip). The child may have difficulty swallowing and may vomit through the nose.
Ear and hearing problems. Frequent ear infections cause hearing loss. Difficulty in learning to speak follows.
Defective immunity. The thymus gland does not develop, and this causes a deficiency of T cell-dependent immunity.
Other possible problems include frequent infections, spine deformity (scoliosis), short stature, and mental health problems in adulthood. There are no typical symptoms of DiGeorge syndrome. Affected children may have a few or all of the described manifestations. Heart defects and immune deficiency may be severe enough to cause death during childhood, but some people with this syndrome reach adulthood without knowing about it.
Those with mild manifestations of the DiGeorge syndrome may reach adulthood and be able to live an independent life, though their life expectancy is shortened.
22q11.2 Deletion Syndrome
Several syndromes with similar and overlapping manifestations were described before genetic testing became available:
- DiGeorge syndrome
- Velocardiofacial syndrome (also called Shprintzen syndrome)
- Conotruncal anomaly face syndrome
- Cayler cardiofacial syndrome
- Opitz syndrome
- Sedlackova syndrome
- CATCH 22 syndrome
After genetic testing was introduced, all these disorders were found to have 22q11.2 deletion. All of them are now included in the 22q11.2 deletion syndrome.
Human beings have 46 chromosomes in the nucleus of each cell. Of these, 44 (called the autosomes) are in pairs numbered from 1 to 22. The other two are the sex chromosomes (X and Y). Each chromosome has two parts, named p and q. The 22q11.2 deletion is a loss of some of the genetic material from the q part of chromosome 22. About 30 to 40 genes are lost, and the manifestations and their severity depend on the amount of genetic material missing.
What Causes 22q11.2 Deletion?
How did this happen? Will it happen again? These questions will be at the forefront of your mind if your child is diagnosed with 22q11.2 deletion syndrome.
Most cases occur randomly. About 90% of people with this genetic disorder have no inheritance. One child in 10 gets the gene deletion from a parent. Since the deletion can cause very mild manifestations and remain undiagnosed, both you and your partner should have yourselves tested.
This is a genetic disorder and is not caused by anything you did, ate, or drank before or during pregnancy.
Treatment of 22q11.2 Deletion Syndrome
At present, there is no treatment for such chromosomal disorders. Millions of nucleated cells in the body each have a copy of the defective chromosome, and it isn't possible to correct this. Since the problems with this syndrome are variable, each person needs a customized treatment plan. Some measures your doctor will recommend include:
- Regular tests of development, growth, and hearing
- Regular testing for immune function
- Monitoring and treatment of the heart defects — this may require surgery
- Physiotherapy to train muscles and develop strength for tasks like walking and running
- Occupational therapy for developing fine skills like tying shoelaces and writing
- Speech therapy to overcome speech problems — this may have to wait until a cleft palate is repaired
- Counseling by a psychotherapist for mental health problems
Learning disabilities are an important component of this syndrome. These children have a high prevalence of intellectual disability. Common problems are deficits in attention, visual-spatial processing, attention, working memory, verbal learning, arithmetic, and language. Some of them have relative strengths in specific reading and spelling skills.
Immune deficiency in the 22q11.2 deletion syndrome can cause repeated severe infections. Transplants of cultured unrelated thymic tissue can correct immune function. Bone marrow transplants also help improve immune function.
A team of plastic surgeon, a maxillofacial surgeon, and others may be needed to correct defects of the palate, lip, and throat. An endocrinologist may be needed if your child has parathyroid hormone deficiency. The low blood calcium levels caused by this hormone deficiency can be serious, and your doctor may prescribe calcium and vitamin D supplements.
Will It Happen Again?
If neither parent has this deletion, future children have about a 1 in 100 risk of this disorder. This is higher than the population risk, which is about 1 in 4,000.
If one of you is carrying this gene deletion, your future children could inherit it. People carrying this deletion have one normal chromosome 22 and one with the deletion. Children have a 50% chance of inheriting the abnormal chromosome. Since chance has no memory, each pregnancy carries the same 50% risk.
If one of your children was diagnosed with this syndrome or someone in your family has it, you should talk to your doctor. Your doctor will advise prenatal testing for this disorder during early pregnancy. Chorionic villus sampling or amniocentesis is used to obtain fetal blood for genetic testing. The results will show whether your baby has the 22q11.2 deletion but cannot predict how severe it will be.