Microdeletion Syndrome 22Q11: Causes, Symptoms & Treatment

Microdeletion syndrome 22q11 refers to chromosomal abnormalities that affect the long arm of chromosome 22 in gene locus 22q11 and manifest as malformation syndromes. In most cases, affected individuals suffer from a heart defect, fascial malformations and thymic hypoplasia. Treatment is symptomatic and focuses mainly on the correction of malformed organs.

What is 22q11 microdeletion syndrome?

Chromosomal aberrations are structural or numerical abnormalities in the genetic material. Most chromosomal aberrations represent a major defect in genetic material. Chromosomal abnormalities can result, for example, from a deletion. In each deletion, a portion of the chromosome arm is lost. There are different disease patterns and syndromes based on chromosomal aberrations. One of them is the so-called microdeletion syndrome 22q11, which includes various disorders caused by changes in position 11 of chromosome 22. Among the best known of these disorders are DiGeorge syndrome and Shprintzen syndrome, also known as velo-cardio-facial syndrome. The name of the syndromes as CATCH-22 syndrome is also common, as is the expression of microdeletion syndromes 22q11. GiGeorge syndrome and Shprintzen syndrome merge smoothly and share many symptoms with each other. However, disorders from the microdeletion syndrome 22q11 group are fundamentally characterized by symptomatic diversity.

Causes

The cause of all microdeletion syndromes 22q11 are pathological changes on the long arm of chromosome 22 with position 11. More precisely, these changes are the smallest variant of deletion. Deletion is the loss of a DNA segment. Thus, the anomaly corresponds to a gene mutation. The microdeletion 22q11.2 leads to developmental field defects of the pharyngeal pockets and the gill arch, for example, due to base losses. As a consequence, the vessels close to the heart, the thymus and the parathyroid glands of the patients are affected by malformations. Since the term microdeletion syndrome 22q11 is a collective term for various deletion syndromes, not all of the described symptoms have to occur in individual cases. Also the expression can differ significantly from case to case. All syndromes in the 22q11 microdeletion syndrome group have a partly hereditary basis, although new mutations may also occur.

Symptoms, complaints, and signs

Due to microdeletions in the 22q11 gene locus, patients of the syndromes suffer from more or less severe cardiac defects such as ventricular septal defect. In addition to malformations of the vessels, preferably in the region of the aortic arch, hypoparathyroidism may be an indication for the presence of the syndrome. The missing or defective formation of the thymus can also be a symptom. In most cases, facial malformations such as cleft lip and palate and micrognathia are also present. Renal involvement up to renal agenesis is also common. Some patients have a conspicuously broad nasal root, an especially long nasal bridge, or a broad nasal tip. In addition, hypertelorism with an antimongoloid eyelid axis may be indicative of the microdeletion syndrome. The same is true for a short philtrum or auricular dysplasia. Thymic hypoplasia can cause T-lymphocyte]] deficiency, which in the course results in severe infections. Calcium deficiency may follow defects of the adrenal glands due to hormone deficiency. In turn, seizures often develop from calcium deficiency. The severity and distribution of symptoms depends on the individual case and especially on the type of microdeletion.

Diagnosis and course of the disease

The initial tentative diagnosis of 22q11 microdeletion syndrome can be made on the basis of combined occurrence of characteristic malformations. Malformations of the heart are often the first clue that, paired with facial or glandular abnormalities, can establish a tentative diagnosis. Differentially, the floating harbor syndrome must be differentiated. Molecular genetic analyses are used to confirm the diagnosis. Detection of a 22q11 deletion can be achieved mainly by fluorescence in situ hybridization. The prognosis of patients differs from case to case. Especially the organ involvement, the treatability and the severity of the individual malformations determine the course of the syndromes.

Complications

As a result of 22q11 microdeletion syndrome, affected individuals usually suffer from various malformations and deformities that can significantly limit and reduce their quality of life. Primarily, patients also suffer from a heart defect. If this is not treated, in the worst case it can also lead to cardiac death of the patient. The face is affected by various malformations, so that children in particular can suffer from teasing and bullying. There is the development of a cleft palate and also complaints of the kidneys. Furthermore, there are also complaints in the ears, so that a slight hearing loss can occur. The microdeletion syndrome 22q11 also leads to cramps and thus to severe pain in the muscles. Not infrequently, parents and relatives of the child are also affected by psychological complaints or depression caused by microdeletion syndrome 22q11. A causal treatment of the syndrome is not possible. Therefore, only the symptoms can be limited so that everyday life becomes more bearable for the affected person. Complications do not occur. However, a complete cure is usually not possible. Microdeletion syndrome 22q11 also does not usually result in a reduced life expectancy.

When should you see a doctor?

Microdeletion syndrome 22q11 is a genetic disorder whose symptoms are usually noticed immediately at birth. Disturbances in heart activity and resulting problems with heart rhythm are signs of an existing irregularity. Newborns often see the light of day with an optical deformity. In case of a cleft lip and palate, immediate medical treatment becomes necessary. Optical changes in the shape of the nose, abnormalities in the spacing of the eyes or other facial deformities indicate a condition that must be examined and treated. In the case of an inpatient birth, the nurses and doctors present take over the necessary steps for adequate medical care of the child in a routine procedure. Midwives perform the same tasks in a home birth and a birth in a birth center. In these cases, the parents do not have to take action on their own. If an unexpected spontaneous birth occurs without the presence of doctors or nursing staff, a medical examination of mother and child is always necessary as soon as possible. An ambulance service should be alerted so that adequate care can be provided. If the newborn child shows seizures, problems with breathing or movement disorders, an intensive examination is necessary. Various medical tests will be performed to determine the cause of the symptoms and symptomatic treatment will be initiated.

Treatment and therapy

The cause of 22q11 microdeletion syndromes lies in the genes. Gene therapy approaches are currently being explored but have not yet reached the clinical stage. For this reason, no therapy is yet available that can address the cause of the symptoms. Therefore, instead of causal therapies, patients receive symptomatic treatment combined with supportive measures. An interdisciplinary team of physicians cares for those affected. The initial focus of symptomatic treatment is the correction of all life-threatening malformations. The malformations with the highest priority are usually heart defects or the non-formation of other organs. Invasive surgical procedures are usually the treatment of choice here. The thymus, for example, can be replaced by transplantation. In addition, calcium and vitamin D substitutions are initiated in cases of corresponding deficiency. Hormone substitutions may also be necessary in individual cases, depending on the symptoms. If there is a susceptibility to infections and the patient has to deal with repeated infections, these infections are brought to an end with conservative drug therapies. Malformations of the face and purely plastic symptoms of other kinds can be countered with plastic surgery under certain circumstances. However, these treatment steps are usually put on the back burner because the more serious defects must be corrected first.

Outlook and prognosis

When considering prognosis, a distinction must be made between life expectancy and quality of life. For 22q11 microdeletion syndrome, a favorable outlook emerges under certain conditions.In this way, patients with the disease reach a normal old age, provided that there are no serious concomitant circumstances such as a heart defect or an immune deficiency. Doctors try to correct organic malformations at an early stage by means of surgical interventions. If this is successful, the probability of many years of freedom from symptoms increases. Only about four percent of all infants die from the microdeletion syndrome 22q11. The quality of life is not infrequently reduced by visually perceptible blemishes. Plastic surgery has meanwhile developed sufficient procedures to counteract a psychosocial burden. Such cosmetic surgery takes place after correction of life-threatening defects. If accompanying therapies are claimed at an early stage, sufferers are most likely to be able to lead a self-determined life as adults. Others, however, require care in certain situations. As a rule, it is possible to work. Patients with microdeletion syndrome 22q11 feel most comfortable in a stable environment. Therapeutic measures, medication and the use of assistive devices are part of everyday life, either permanently or acutely. If parents forgo treatment, life expectancy and quality of life are significantly reduced.

Prevention

To date, few preventive measures are available for the prophylaxis of disorders from the microdeletion syndrome 22q11 group. Because of the heritability of many associated syndromes, genetic counseling during the family planning phase in particular can be described as a preventive measure in the broadest sense. If the results are appropriate, couples may decide against having their own children and in favor of adoption.

Follow-up

The person affected by chromosomal aberrations such as microdeletion syndrome 22q11 often has no or very few aftercare measures available to him or her. It focuses on helping them cope better with the disease and improving their quality of life. Since it is a genetic disease, it cannot be completely cured. Therefore, genetic testing and counseling should always be done if a child is desired to prevent chromosomal aberrations from occurring in the children. The further treatment depends very much on the exact manifestation of the disease, so that no general prediction can be made. Possibly the life expectancy of the affected person is also reduced. In this case, efforts and stressful or physical activities should be avoided in any case. Likewise, most affected persons are also dependent on the help and support of their own family to cope with everyday life due to the chromosomal aberrations. Intensive and loving conversations are often necessary to avoid psychological upsets or depression. If necessary, a psychologist should clarify whether therapy should be used.

This is what you can do yourself

Due to the microdeletion syndrome 22q11, patients suffer from birth from severe malformations that affect the heart, other internal organs as well as the face. Initially, the quality of life is impaired, especially by the heart defect. The parents accompany the sick child during necessary stays in the clinic. Usually, various surgical interventions are necessary to correct the organic malformations. Since the facial deformities are usually an aesthetic blemish for the patients and their parents, surgical interventions are also used here if desired. For example, the doctors correct a cleft palate and jaw. In addition, those affected receive drug treatment, for example with regard to the defects of the thymus. The parents take care of the correct dosage of the medicines, as the child patients cannot be expected to take responsibility for this. If the patients are physically able, they usually attend a special school and receive valuable educational support there. Some children also attend a regular school as part of inclusion and are quite capable of performing as required there. The quality of life is often improved by school attendance, as the affected children make the acquaintance of other children with the disease. For the parents, the disease represents a great psychological challenge, which in some cases leads to emotional difficulties. It is then important for the parents to consult a psychotherapist.