In the Loote Ultrahelikeskus we offer the screening test for DiGeorge Syndrome
About one in 2000-4000 live births experiences 22q11.2 deletion syndrome which could cause several congenital disorders and also an average up to moderate mental disorder.
22q11.2 is one of the most common probabilities of development disorders and congenital heart diseases, only slightly less than Down syndrome. These two syndromes are similar, as both have many symptoms of disease, including low muscle tone.
What is 22q11.2 deletion syndrome?
22q11.2 deletion syndrome, i.e. DiGeorge syndrome is caused by the absence of small piece of longer shoulder of the 22nd chromosome.
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The resulting condition has an impact on the major part of the body. Most of the children with the syndrome have heart failures, immune disorders and specific, although hardly noticeable, features. Almost all of them have average up to moderate mental disorder and delayed language and speech development. Some children have lack of calcium, kidney problems, eating problems, cramps or other health problems. Approximately one out of five children with 22q11.2 deletion syndrome has the autism spectrum disorder and one out of four young adults suffers from psychiatric disorder, such as schizophrenia. The infants with severe heart problems or immune system disorders have higher risk to die. The people with 22q11.2 deletion syndrome who survived their childhood could have shorter lifetime and higher risk of sudden death.
What is the reason of 22q11.2 deletion syndrome?
Most of the people with 22q11.2 deletion syndrome have 3 MB deletion (involves in average 40 genes) on one copy of the 22nd chromosome. 22q11.2 deletion is occasional and is mostly not hereditary. However, approximately 7% of the children with syndrome, as known, inherited this from their parent who was sick with the same condition. The testing of both parents could help to determine the likelihood of re-occurrence of such condition in case of the next pregnancy.
Why is the diagnosing of 22q11.2 deletion syndrome important?
The treatment of conditions listed as follows and the combination of physiotherapy, work therapy and special training could improve the life quality of patients with 22q11.2 deletion syndrome.
- Hypocalcemia. Low level of calcium, i.e. hypocalcemia, is common in case of 22q11.2 deletion syndrome, foremost in case of newborns. This is due to the deficient functioning of ear thyroids. The lack of calcium caused by the deficiency of parathyroid hormone could result in cramps. The reasons of cramps caused by low level of calcium are often left unattended, thus the problem could remain without treatment and influence the mental development of the child. The newborns with 22q11.2 deletion syndrome should be observed as to the signs of hypocalcemia and if these are established, the child should be immediately treated. Hypocalcemia could recur during growth spurts, puberty or during illness and pursuant to the operations.
- Immunodeficiency
The lymphatic system is an important part of immune system which protects a child against infections. The parts of the lymphatic system are spleen, thymus, lymph nodes and vessels, also tonsils and adenoids. About 75% of the children with 22q11.2 deletion syndrome have immunodeficiency. Due to the risk of immunodeficiency the children having syndrome should be checked prior to taking live virus vaccines.
- Palate malformations. Approximately 75% of the children suffering from the syndrome have the palate problem which is either structural or functional or their combination. This problem could cause eating difficulties and/or speech disorders. If the problem is not fixed in good time, it could influence the development of speech. Such condition can be mostly treated.
- Eating difficulties. The newborns with 22q11.2 deletion syndrome have often eating difficulties which are not caused by the palate or heart failures. The reason of eating difficulty could be the motor disorder of muscles of pharynx and larynx, the most common symptoms of which are reflux and constipation. The intestinal malrotation and Hirschsprung’s disease could seldom occur. Most of these problems can be treated.
- Congenital heart failures. Approximately 75% of the persons with the syndrome have congenital heart failure; such indicator is often the basis for diagnosing the syndrome. If 22q11.2 deletion syndrome is diagnosed for the patient, he/she should be referred to the visit of the cardiologist. Many heart failures are operable today.
- 22q11.2 deletion syndrome also involves other medical problems, including kidney problems, loss of hearing, ear-nose-throat complications, autoimmune diseases, growth retention and skeletal system problems.
How should I relate to the high risk result of Panorama test as to 22q11.2 deletion syndrome?
The sensitivity of Panorama test in detecting 22q11.2 microdeletion is 95.7% and specificity > 99%. Thus this is an accurate screening test.
However, regardless of the accuracy, Panorama test will be still a screening test. At the absence of the ultrasound markers the estimated positive value of Panorama test is only 20%. At the same time in case of positive ultrasound finding (heart failure, small thymus) the estimated positive value of Panorama is close to 100%. Thus this is not a diagnostic test. In case of Panorama test with high risk the amniotic fluid test or chorion biopsy confirming the diagnosis should be performed. This also involves submicroscopic chromosome-analysis which is able to detect the missing piece of the 22nd chromosome causing 22q11.2 deletion syndrome. If a woman does not require an invasive test during pregnancy, the chromosomes received from the vein blood of the newborn after birth could be examined with the help of submicroscopic chromosome analysis.
The estimated negative value of Panorama test as to 22q11.2 is 99.9%. Thus, the possibility that Panorama test is not recognizing the disease is very little.
The sensitivity of Panorama test in detecting DiGeorge syndrome depends on the amount of cell-free fetal DNA. If the amount of cell-free fetal DNA by screening negative women is higher than 6.5%, the fetal risk pursuant to 22q11.2 microdeletion test is 1:9000 per one birth which could be considered very reassuring.
Can 22q11.2 syndrome be tested also in case of twin pregnancy?
22q11.2 syndrome can be tested only in case of monochorionic twins (twins sharing one placenta and are always monozygotic twins). 22q11.2 syndrome could not be tested in case of dichorionic twins (twins having their own placenta and could be either monozygotic or dizygotic twins) and in case of IVF pregnancy, provided donor eggs have been used.