Materiały źródłowe

• #1 Premature death in adults with 22q11.2 deletion syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3188306/

  22q11.2 deletion syndrome (22q11.2DS) is a multisystem disease with a prevalence of 1/4000. Variable expression of congenital and later onset features contributes to its under-recognition. Longevity in those surviving childhood is believed to be normal but data are limited. […] Individuals with 22q11.2DS who survive childhood have diminished life expectancy and increased risk of sudden death not attributable to any single factor. Some sudden and/or premature deaths observed in the general population may represent undiagnosed 22q11.2DS. Increased recognition of the syndrome by family doctors, specialists and coroners will be essential to facilitate the tissue studies needed to determine underlying mechanisms. […] The results demonstrate that individuals with 22q11.2DS who survive to adulthood are at elevated risk of premature death when compared with their unaffected siblings.

• #2

  https://link.springer.com/article/10.1007/s10875-022-01418-y

  Current practices vary widely regarding the immunological work-up and management of patients affected with defects in thymic development (DTD), which include chromosome 22q11.2 microdeletion syndrome (22q11.2del) and other causes of DiGeorge syndrome (DGS) […] The lack of consensus and widely varying practices highlight the need to establish updated immunological clinical practice guidelines. These guideline recommendations provide a comprehensive review for immunologists and other clinicians who manage immune aspects of this group of disorders. […] The small deletion within chromosome 22 was linked to DiGeorge syndrome in the early 1980s, although this syndrome was named in 1965 when Angelo DiGeorge described the common embryologic derivation of the heart, thymus, and parathyroid glands. The classic phenotypic triad of DGS consists of conotruncal heart defects, hypocalcemia due to hypoparathyroidism, and T cell deficiency due to thymic hypoplasia.

• #3 DiGeorge Syndrome: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/886526-overview

  Although the prognosis for 22q11.2DS varies widely, depending largely on the nature and degree of involvement of different organs, many adults live long and productive lives. […] The prognosis for 22q11.2DS varies widely, depending largely on the nature and degree of involvement of different organs, and it is important to note that many adults do live long and productive lives. […] The most common cause of mortality in 22q11.2DS is a congenital heart defect and the second most common is severe immune deficiency. Mortality is higher in infancy because of the severity of these 2 conditions. Infants with thymus aplasia present with severe immunodeficiency and typically die of sepsis, caused by either bacterial or fungal infections. […] In a large European collaborative study, 558 patients with 22q11.2DS were evaluated using a questionnaire. Eight percent of the patients died, with more than half of the deaths occurring within the first month of life and the majority happening within 6 months of birth. Of the patients who survived, 62% had only mild learning problems or were developmentally normal. All the deaths except one were attributable to congenital heart disease. In this study, only 11% of patients were older than 18 years. Adult mortality data are limited. In one study, researchers compared survival of 102 adults (17 yrs) with 22q11.2DS to survival of their 162 unaffected siblings. The study found survival in the affected group was reduced with an average age of death of 41.5 years (47.3 years in those without major congenital heart disease).

• #4 Premature death in adults with 22q11.2 deletion syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3188306/

  Notably, deaths in 22q11.2DS occurred at average age 41.5 years overall (47.3 years in those with no major CHD), much earlier than Canadian general population expectations: age 80.4 (both sexes); 78.0 (males); 82.7 (females) years. […] The causes of premature death in adults with 22q11.2DS are likely multifactorial and both cardiac and non-cardiac in origin. […] Strikingly, the most common cause of death observed was unexplained sudden death in six (6%) of 102 subjects. […] Studies following larger numbers of patients with 22q11.2DS prospectively over decades will provide more details about clinical risk factors for death as an outcome of the syndrome, including possible effects of associated medical and psychiatric illnesses, medications, lifestyle and other factors.

• #5 All-cause mortality and survival in adults with 22q11.2 deletion syndrome | Genetics in Medicine

  https://www.nature.com/articles/s41436-019-0509-y

  KaplanMeier curves showed significantly lower survival in adults with 22q11.2DS compared with their unaffected siblings (log rank 2=59.7, df=1, p<0.0001). [...] Within the 22q11.2DS cohort, there was a significant effect of major CHD on survival that was apparent by early adulthood (log rank 2=19.5, df=1, p<0.0001). [...] The probability of survival to ages 40 and 50 years was approximately 82% and 63%, respectively, for those with major CHD, and 98% and 85%, respectively, for those with no major CHD. [...] The results of this study demonstrate that, compared with their closest relatives, individuals with 22q11.2DS had a higher risk of all-cause mortality that was significantly related to both global effects of the 22q11.2 deletion and more complex CHD that is often associated with the syndrome.

• #6 All-cause mortality and survival in adults with 22q11.2 deletion syndrome | Genetics in Medicine

  https://www.nature.com/articles/s41436-019-0509-y

  Given limited data available on long-term outcomes in 22q11.2 deletion syndrome (22q11.2DS), we investigated mortality risk in adults with this microdeletion syndrome. […] The 22q11.2 deletion (hazard ratio [HR] 8.86, 95% CI 2.8727.37) and major congenital heart disease (CHD; HR 5.03, 95% CI 2.2711.17), but not intellectual disability or psychotic illness, were significant independent predictors of mortality for adults with 22q11.2DS compared with their siblings. […] For adults with 22q11.2DS, the 22q11.2 deletion and more severe forms of CHD both contribute to a lower life expectancy than family-based expectations. […] The 22q11.2 deletion (HR 8.86, 95% CI 2.8727.37, p=0.0002) and the presence of a major CHD (HR 5.03, 95% CI 2.2711.17, p<0.0001) were independent factors associated with increased risk of all-cause mortality in adults with 22q11.2DS, when controlling for other covariates.

• #7 Mortality in Patients with 22q11.2 Rearrangements

  https://www.mdpi.com/2073-4425/15/9/1146

  The 22q11.2 region is highly susceptible to genomic rearrangements leading to multiple genomic disorders, including 22q11.2 microdeletion syndrome (22q11.2 DS) (MIM# 188400), 22q11.2 microduplication syndrome (MIM# 608363), supernumerary der(22)t(11;22) syndrome (also known as Emanuel Syndrome; MIM# 609029), and Cat Eye Syndrome (MIM# 115470). […] Previous studies have shown that mortality in pediatric patients has a median age of 5 years in which the main cause of death is due to congenital heart disease. […] It has also been shown that they die prematurely in comparison to their unaffected siblings. […] The median age of death was 3 months and 18 days (ranging from 3 days to 34 years). […] Mortality from cardiac causes accounted for 71.42%. […] The second most frequent cause of death was sepsis in two patients (9.52%).

• #8 Mortality in Patients with 22q11.2 Rearrangements

  https://www.mdpi.com/2073-4425/15/9/1146

  This study adds additional information on mortality in one of the largest cohorts of patients with 22q11.2 rearrangements in more than 30 years of follow-up. […] The mortality of 22 q11.2 deletions is higher than in other rearrangements but we cannot conclude whether 22q11.2 rearrangements themselves represent an independent risk factor for mortality after cardiac surgery. […] Overall, the most frequent cause of death was cardiovascular in nature, either as a single cause of death or in combination with other factors, representing 71.42% of deaths. […] The vast majority had severe heart defects, mainly interrupted aortic arch, TOF, and pulmonary valve atresia, among others. […] In our cohort, patients died much earlier compared to previous studies, suggesting that other factors may interfere with mortality, not only due to cardiac causes but also extracardiac, having a multifactorial nature.

• #9

  https://omim.org/entry/188400

  DiGeorge syndrome is characterized by neonatal hypocalcemia, which may present as tetany or seizures, due to hypoplasia of the parathyroid glands, and susceptibility to infection due to a deficit of T cells. The immune deficit is caused by hypoplasia or aplasia of the thymus gland. A variety of cardiac malformations are seen in particular affecting the outflow tract. These include tetralogy of Fallot, type B interrupted aortic arch, truncus arteriosus, right aortic arch and aberrant right subclavian artery. […] Jawad et al. (2001) studied 195 patients with chromosome 22q11 deletion syndrome and found that diminished T-cell counts in the peripheral blood are common. The pattern of changes seen with aging in normal control patients was also seen in patients with the chromosome 22q11.2 deletion syndrome, although the decline in T cells was blunted. Autoimmune disease was seen in most age groups, although the types of disorders varied according to age. Infections were also common in older patients, although they were seldom life-threatening.

• #10

  https://link.springer.com/article/10.1007/s10875-022-01418-y

  The quantitative number of T lymphocytes measured in the blood of individuals with 22q11.2del largely reflects the thymic output and thymic size, particularly in the neonatal period. Thus, barring a specific T cell defect such as SCID, a normal thymic volume in 22q11.2del results in a normal number of T cells, whereas a small thymus can result in a quantitative T cell deficiency. An estimated 67-80% of individuals affected with 22q11.2del have some degree of T cell lymphopenia (TCL). […] These guidelines are directed mainly toward individuals with 22q11.2del/DGS. Although data is limited, they may also be applicable to other causes of DTD. Background information provided is intended to provide an understanding and rationale for the recommendations involving the diagnosis and management of abnormal thymic development.

• #11

  https://link.springer.com/article/10.1007/s10875-022-01418-y

  In individuals with 22q11.2del with only mild to moderate T cell lymphopenia, T cell numbers do not predict susceptibility to infections. Immunoglobulin and other humoral abnormalities in 22q11.2del have been increasingly recognized in recent years. Even individuals whose immune evaluation may be normal early in life are at increased risk for development of IgG deficiency, which may progress to a clinical and biologic picture analogous to CVID. […] The workgroup consensus is that the terms partial, complete, and atypical DiGeorge be substituted with more descriptive nomenclature that directly characterizes the degree of TCL and will be universally understood and accepted. Affected individuals have either normal quantitative T cell values, TCL (mild or significant), or severe TCL suggesting congenital athymia. […] In summary, the prognosis for individuals with 22q11.2 deletion syndrome varies significantly based on the degree of T cell deficiency and associated clinical features. The establishment of comprehensive guidelines aims to improve the management and outcomes for affected individuals.

• #12 Mortality in Patients with 22q11.2 Rearrangements

  https://www.mdpi.com/2073-4425/15/9/1146

  In total, 13 out of 21 patients underwent cardiac surgery (61.9%). […] In our study, the majority of the patients have been surgically intervened on in the late 90s and early 2000s. Over the last few decades, there have been advances in cardiac surgeries, which led to an increased survival rate of these patients. […] This study adds information on the causes of mortality in patients carrying 22q11.2 rearrangements.

• #13 22q11.2 deletion syndrome | Dayton Children’s Hospital

  https://www.childrensdayton.org/patients-visitors/services/craniofacial-center/conditions-we-treat/22q112-deletion-syndrome

  One to two percent of children born with this syndrome have a life expectancy of two to three years; however, most individuals reach adulthood and can live a life span into the fifties. Early treatment should be considered for the most severe issues with this condition to prolong life expectancy. […] Treatment is focused on the management of the symptoms to improve quality of life. This may involve medications for infections, supplements and diet management, cleft palate and heart surgeries. Various therapies such as physical, occupational, speech, stem cell and hormone therapies may be needed.

• #14

  https://omim.org/entry/188400

  Bassett et al. (2005) described the phenotypic features of 78 adults with 22q11 deletion syndrome and identified 43 distinct features present in more than 5% of patients. Common characteristic features included intellectual disabilities (92.3%), hypocalcemia (64%), palatal anomalies (42%), and cardiovascular anomalies (25.8%). Other less commonly appreciated features included obesity (35%), hypothyroidism (20.5%), hearing deficits (28%), cholelithiasis (19%), scoliosis (47%), and dermatologic abnormalities (severe acne, 23%; seborrhea, 35%). Significantly, schizophrenia was present in 22.6% of patients. […] Cheung et al. (2014) used a logistic regression model to investigate potential predictors of intellectual disability severity, including neonatal hypocalcemia, neonatal seizures, and complex congenital heart disease in 149 adults with 22q11.2 deletion syndrome, 10 of whom had moderate to severe intellectual disability. The model was highly significant (p less than 0.0001), showing neonatal seizures (p = 0.0018) and neonatal hypocalcemia (p = 0.047) to be significant predictors of a more severe level of intellectual disability. Neonatal seizures were significantly associated with hypocalcemia in the entire sample, regardless of intellectual level.

• #15 DiGeorge syndrome (22q11 deletion)

  https://www.nhs.uk/conditions/digeorge-syndrome/

  DiGeorge syndrome is a condition present from birth that can cause a range of lifelong problems, including heart defects and learning difficulties. […] The severity of the condition varies. Some children can be severely ill and very occasionally may die from it, but many others may grow up without realising they have it. […] Everyone with DiGeorge syndrome is affected differently and it’s difficult to predict how severe the condition will be. Most children survive into adulthood. […] Many people with DiGeorge syndrome who reach adulthood will have a relatively normal life span, but ongoing health problems can sometimes mean their life expectancy is a bit lower than usual. It’s important to attend regular check-ups so that any problems can be found and treated early.

• #16 DiGeorge Syndrome (22q11.2 Deletion Syndrome): What It Is, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/21182-digeorge-syndrome

  DiGeorge syndrome is a lifelong condition without a cure. Your outlook depends on the severity of your symptoms. Some of your symptoms could be life-threatening, especially if they affect your heart. With ongoing treatment and support, adults diagnosed with DiGeorge syndrome live active and fulfilling lives with limited interruption from their condition. […] Most people diagnosed with DiGeorge syndrome have a normal life expectancy with mild symptoms. Severe symptoms can lead to a shortened life expectancy without treatment.

• #17 DiGeorge Syndrome/Velocardiofacial Syndrome: The Chromosome 22q11.2 Deletion Syndrome | SpringerLink

  https://link.springer.com/chapter/10.1007/978-0-387-72005-0_4

  Chromosome 22q11.2 deletion (CH22qD) syndrome is also known as DiGeorge syndrome or velocardiofacial syndrome. This deletion syndrome is extremely common with nearly one in 4000 children being affected. Recent advances and a holistic approach to patients have improved the care and well-being of these patients. […] Patients will most often need interventions directed at maximizing function for many organ systems but can ultimately have a high level of functioning.

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