Materiały źródłowe

• #1 DiGeorge Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549798/

  DiGeorge syndrome (DGS) is a congenital disorder with a broad phenotypic presentation, which results predominantly from the microdeletion of chromosome 22 at a location known as 22q11.2. […] About 90% of DGS cases are a result of a deletion in chromosome 22, more specifically on the long arm (q) at the 11.2 locus (22q11.2). Most of these mutations arise de novo with no genetic abnormalities noted in the genome of the parents of children with DGS. […] Researchers have identified over 90 different genes at this locus, some of which they have studied in mouse models. The most studied of these genes is T-box transcription factor 1 (TBX1), which correlates with severe defects in the development of the heart, thymus, and parathyroid glands of mouse models. TBX1 also correlates with neuromicrovascular anomalies, which may be responsible for the behavioral and developmental abnormalities seen in DGS.

• #1 DiGeorge syndrome (22q11.2 deletion syndrome) – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/digeorge-syndrome/symptoms-causes/syc-20353543

  DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a condition caused when a small part of chromosome 22 is missing. This deletion causes several body systems to develop poorly. […] Each person has two copies of chromosome 22 one inherited from each parent. If a person has DiGeorge syndrome, one copy of chromosome 22 is missing a segment that includes an estimated 30 to 40 genes. Many of these genes haven’t been clearly identified and aren’t well understood. The region of chromosome 22 that’s deleted is known as 22q11.2. […] The deletion of genes from chromosome 22 usually occurs as a random event in the father’s sperm or in the mother’s egg. Or it may occur early when the baby is developing. Rarely, the deletion is passed to a child from a parent who also has a deletion in chromosome 22 but may have fewer or mild symptoms.

• #1 DiGeorge syndrome – Wikipedia

  https://en.wikipedia.org/wiki/DiGeorge_syndrome

  DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by a microdeletion on the long arm of chromosome 22. […] DiGeorge syndrome is typically due to the deletion of 30 to 40 genes in the middle of chromosome 22 at a location known as 22q11.2. About 90% of cases occur due to a new mutation during early development, while 10% are inherited. […] DiGeorge syndrome is caused by a heterozygous deletion of part of the long arm (q) of chromosome 22, region 1, band 1, sub-band 2 (22q11.2). Approximately 80-90% of patients have a deletion of 3 Mb and 8% have a deletion of 1.5Mb. […] The exact mechanism that causes all of the associated features of the syndrome is unknown. Of the 3050 genes in the deleted region, a number have been identified as possibly playing a role in the development of some of the signs and symptoms.

• #1 DiGeorge syndrome (22q11.2 deletion syndrome) – The Oncofertility Consortium

  https://oncofertility.msu.edu/non-malignant-conditions/digeorge-syndrome-22q11-2-deletion-syndrome/

  DiGeorge syndrome is caused by a 1.5-3 Mb hemizygous deletion of chromosome 22q11.2. […] In a majority of cases of DiGeorge Syndrome, the deletion is mediated by homologous recombination between these low copy number repeats. […] Haploinsufficiency of TBX1 is responsible for major phenotypes that are seen in individuals with DiGeorge syndrome. […] However, the variability of phenotypic features with a deletion of TBX1 suggests that altered interaction with downstream genes and environmental effects also affect the disease presentation. […] As in all microdeletion syndromes, inheritance is autosomal dominant, however most cases of DiGeorge syndrome result from a de novo microdeletion.

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

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

  DiGeorge syndrome (DGS) is one of a group of phenotypically similar disorders including velocardiofacial syndrome (VCFS, or Shprintzen syndrome) and conotruncal anomaly face (CTAF) syndrome that share a microdeletion of chromosome 22q11.2, a region known as the DGS critical region. […] The syndrome is caused by a microdeletion of band 22q11.2. The long arm of chromosome 22 (at q11) is prone to a microdeletion because of the presence of eight nonallelic, flanking, low-copy repeat DNA sequence clusters (LCR22) labeled AH. […] The most common deletion present in 85% of individuals is 3 million base pair (Mb) in size, extends from A to D, and encompasses approximately 40 genes and 4 micro RNAs. […] Among other genes mapped in the deleted region that have been implicated in the pathogenesis of 22q11.2DS include HIRA and UFD1L.

• #1 DiGeorge syndrome (22q11.2 deletion syndrome)

  https://johnsonmemorial.org/jmh-health/disease-conditions/con-20319021

  DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a condition caused when a small part of chromosome 22 is missing. This deletion causes several body systems to develop poorly. […] Each person has two copies of chromosome 22 one inherited from each parent. If a person has DiGeorge syndrome, one copy of chromosome 22 is missing a segment that includes an estimated 30 to 40 genes. Many of these genes haven’t been clearly identified and aren’t well understood. The region of chromosome 22 that’s deleted is known as 22q11.2. […] The deletion of genes from chromosome 22 usually occurs as a random event in the father’s sperm or in the mother’s egg. Or it may occur early when the baby is developing. Rarely, the deletion is passed to a child from a parent who also has a deletion in chromosome 22 but may have fewer or mild symptoms.

• #1 22q11 deletion syndrome (22q11DS)

  https://www.aboutkidshealth.ca/22q11-deletion-syndrome-22q11ds

  22q11 deletion syndrome (22q11DS) is a genetic condition. […] 22q11DS is a genetic disorder. It results from a small missing piece of genetic material (DNA) on a specific part of chromosome 22. This is called a deletion. […] The 22q11 deletion happens most of the time by chance. In some families, the 22q11 deletion can be inherited from a parent. […] In most cases, 22q11DS is the result of a new genetic change that occurs when a baby is conceived. This is called a de novo deletion and occurs by chance in either the moms egg or the dads sperm. A de novo deletion is not caused by anything the parents did before or during the pregnancy. […] In some people with 22q11DS (about 10%), the deletion is inherited from a parent. Sometimes a parent might not know that they have 22q11DS until after they have a child diagnosed with this condition.

• #1 22q11.2 Deletion Syndrome – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1523/

  22q11.2DS is an autosomal dominant contiguous gene deletion syndrome. […] In 22q11.2DS caused by a 3.0 (2.54)-Mb deletion, the deletion is de novo in more than 90% of individuals and inherited from a heterozygous parent in about 10% of individuals. […] The proportion of individuals with a nested deletion (i.e., a recurrent, atypical shorter deleted segment [LCR22B-D] nested within the large typically deleted region) inherited from an affected parent is higher (60%). […] The term DiGeorge syndrome is now reserved for individuals who have clinical features of 22q11.2DS but do not have an identified 22q11.2 deletion.

• #1

  https://omim.org/entry/188400

  Carelle-Calmels et al. (2009) noted that deletion of 22q11.2, resulting in DGS or VCFS, is usually sporadic but has been reported to be inherited in 6 to 28% of patients with these syndromes. […] Demczuk et al. (1995) pointed to the existence of a strong tendency for 22q11.2 deletions in DGS, VCFS, and isolated conotruncal cardiac disease to be of maternal origin. […] Whereas 90% of cases of DGS may now be attributed to a 22q11 deletion, other chromosome defects have been identified. […] The recognition of the importance of 22q11 deletion grew with improving techniques.

• #1 DiGeorge Syndrome – Causes, Symptoms, Diagnosis, Treatment & Prognosis

  https://www.medindia.net/health/conditions/digeorge-syndrome.htm

  DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a genetic disorder caused by a small deletion in chromosome 22 at position q11.2. The primary cause of DiGeorge syndrome is 22q11.2 deletion, which largely occurs randomly without any identifiable cause. However, in case of about 5-10% children, the 22q11.2 deletion is inherited from a parent suffering from a mild often undiagnosed form of DiGeorge syndrome. […] Approximately 90% of 22q11.2 deletions occur spontaneously during fetal development, while 10% are inherited from a parent. It is an autosomal dominant disorder, which means that a defect in a single chromosome in each cell is sufficient for occurrence of the disorder.

• #1 DiGeorge Syndrome – Developmental and Behavioral Pediatrics – Golisano Children’s Hospital – University of Rochester Medical Center

  https://www.urmc.rochester.edu/childrens-hospital/developmental-disabilities/conditions/digeorge-syndrome.aspx

  The 22q11.2 deletion syndrome (22q11.2DS) is a genetic disorder. […] Most children with 22q11.2DS are missing approximately 46 genes. Researchers dont yet know the exact function of many of these genes. Missing the TBX1 gene on chromosome 22 may likely cause the syndrome’s most common physical symptoms. These include heart problems and cleft palate. […] About 9 in 10 cases of 22q11.2DS happen by chance (randomly). They are present at the time when the egg is fertilized. Or they occur early in a babys growth in the mothers uterus. This means that most children with the disorder have no family history of it. […] But a person with the condition can pass it on to their children. About 1 in 10 cases are inherited from the mother or the father. […] A child is more at risk for this disorder if they have a parent who has the condition or is carrying the faulty chromosome. But most cases occur randomly. […] In about 1 in 10 cases of the syndrome, the deletion is inherited from one of the parents. […] If you have the 22q11.2 deletion, you have a 1 in 2 chance of passing it on to a child. This is true for every pregnancy you have.

• #1 DiGeorge Syndrome (22q11.2 Deletion): Signs, Diagnosis, and Treatment

  https://resources.healthgrades.com/right-care/symptoms-and-conditions/digeorge-syndrome

  Most of the time, the chromosome 22 anomaly happens by chance, and there are no known risk factors. It appears that the 22q11.2 region is vulnerable to deletions. For parents without DiGeorge syndrome, the chance of having a second child with the anomaly is less than 1%. […] Having a parent with the condition is the main risk factor. However, only 10% of people born with the condition inherited it from a parent. Each child has a 50% chance of inheriting the gene and the disorder.

• #1 22q11 deletion syndrome: Genetics

  https://www.aboutkidshealth.ca/22q11-deletion-syndrome-genetics

  22q11DS is known by many names such as velo-cardio-facial syndrome and DiGeorge syndrome. […] 22q11DS is a genetic disorder. It results from a small missing piece of genetic material (DNA) on chromosome 22. This is called a deletion. […] The 22q11 deletion happens most of the time by chance. In some families, the 22q11 deletion can be inherited from a parent. […] 22q11DS is caused by a deletion in chromosome 22. A person will have 22q11DS if one chromosome 22 in the pair has the deletion. […] In some people with 22q11DS (about 10%), the deletion is inherited from a parent. […] Most of the time, 22q11DS is the result of a new genetic deletion that occurs when a baby is conceived. This is called a de novo deletion and occurs by chance in either the moms egg or the dads sperm. […] A de novo deletion is not caused by anything the parents did before or during the pregnancy. […] A person who has 22q11DS has a 50% chance (1 in 2) of having a child with 22q11DS.

• #1 DiGeorge syndrome – Wikipedia

  https://en.wikipedia.org/wiki/DiGeorge_syndrome

  Haploinsufficiency of the TBX1 gene (T-box transcription factor TBX1) is thought to be the cause of some of the symptoms observed. […] The majority cases are a result of a de novo deletion. This is because the 22q11 region has a structure that makes it highly prone to rearrangements during sperm or egg formation.

• #1 DiGeorge or 22q11.2 deletion syndrome | Immune Deficiency Foundation

  https://primaryimmune.org/understanding-primary-immunodeficiency/types-of-pi/digeorge-or-22q112-deletion-syndrome

  DiGeorge syndrome, most frequently caused by a deletion at 22q11.2, is a PI caused by abnormal migration and development of certain cells and tissues during fetal development. […] DGS most commonly occurs in children with 22q11.2 deletion syndrome, CHARGE syndrome, and infants of diabetic mothers. […] The most common cause is due to a genetic defect called 22q11.2 deletion syndrome (22q11.2DS). In children with 22q11.2DS, a piece of chromosome 22 is missing. […] Most cases of 22q11.2 DS occur spontaneously. DGS is caused by a large deletion from chromosome 22. This deletion means that several genes from this region are not present in those with DGS. […] Many of the manifestations of DGS have been linked to deletion of the T-box transcription factor 1 (TBX1) gene on chromosome 22q11, which plays a role in neural crest cell migration, pharyngeal arch (PA) development, and formation of the pharyngeal pouches.

• #1 DiGeorge Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549798/

  DGS results from microdeletion of 22q11.2, which encodes over 90 genes. Patients with DGS display a broad array of phenotypes, and the most common findings include cardiac anomalies, hypocalcemia, and hypoplastic thymus. […] On a genetic basis, TBX1 has correlations with the most prominent phenotypes characteristic of DGS. Failure in embryologic development of the pharyngeal pouches, which is driven by TBX1, leads to absence or hypoplasia of the thymus and parathyroid glands. […] A 22q11.2 knockout mouse model has also been studied, with findings pertinent for molecular and behavioral changes seen in Parkinson’s disease, autism spectrum disorder, attention deficit hyperactivity disorder, and schizophrenia. […] These findings, as well as the neuromicrovascular pathology found in TBX1 knockout mice, suggest a molecular basis for the psychiatric pathologies associated with DGS.

• #1 22q11.2 deletion syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/22q112-deletion-syndrome/

  22q11.2 deletion syndrome is a disorder caused by the deletion of a small piece of chromosome 22. […] Most people with 22q11.2 deletion syndrome are missing a sequence of about 3 million DNA building blocks (base pairs) on one copy of chromosome 22 in each cell. This region contains 30 to 40 genes, many of which have not been well characterized. […] Researchers are working to identify all of the genes that contribute to the features of 22q11.2 deletion syndrome. They have determined that the loss of a particular gene on chromosome 22, TBX1, is probably responsible for many of the syndrome’s characteristic signs (such as heart defects, a cleft palate, distinctive facial features, hearing loss, and low calcium levels). […] The inheritance of 22q11.2 deletion syndrome is considered autosomal dominant because a deletion in one copy of chromosome 22 in each cell is sufficient to cause the condition.

• #1 22q11.2 Deletion Syndrome in Children – Stanford Medicine Children’s Health

  https://www.stanfordchildrens.org/en/topic/default?id=22q112-deletion-syndrome-in-children-90-P01682

  The 22q11.2 deletion syndrome (22q11.2DS) is a genetic disorder. […] Most children with 22q11.2DS are missing 30 to 40 genes. Researchers dont yet know the exact function of many of these genes. But missing the gene TBX1 on chromosome 22 likely causes the syndrome’s most common physical symptoms. These include heart problems and cleft palate. The loss of another gene (called COMT) may also explain the higher risk for behavior problems and mental illness. […] About 9 in 10 cases of 22q11.2DS happen by chance (randomly). They occur when the egg is fertilized. Or they occur early in a babys growth in the mothers uterus. This means that most children with the disorder have no family history of it. […] But a person with the condition can pass it on to his or her children. About 1 in 10 cases are inherited from the mother or the father. When the condition is inherited, other family members could also be affected. A person who has this chromosome deletion has a 1 in 2 chance of passing the problem to a child. […] A child is more at risk for this disorder if he or she has a parent with the condition or is carrying the faulty chromosome. But most cases occur randomly.

• #1

  https://omim.org/entry/188400

  A number sign (#) is used with this entry because DiGeorge syndrome is caused by a 1.5- to 3.0-Mb heterozygous deletion of chromosome 22q11.2. Haploinsufficiency of the TBX1 gene (602054) in particular is responsible for most of the physical malformations. There is evidence that point mutations in the TBX1 gene can also cause the disorder. […] Most cases result from a deletion of chromosome 22q11.2 (the DiGeorge syndrome chromosome region, or DGCR). Several genes are lost including the putative transcription factor TUPLE1 which is expressed in the appropriate distribution. […] A collective acronym CATCH22 has been proposed for these differing presentations. […] DiGeorge syndrome is usually sporadic and results from de novo deletion within chromosome 22. […] The first dominant pedigree in which marked clinical variability was associated with dominant transmission of a 22q11 deletion was reported by Wilson et al. (1991); the mother had the typical dysmorphic features.

• #1 22q11.2 deletion syndrome | Dayton Children’s Hospital

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

  22q11.2 deletion syndrome, also known commonly as DiGeorge syndrome, is a condition that varies greatly in severity among affected individuals (including family members). This condition is caused by a deletion in chromosome 22 near the middle of the chromosome in an area known as q11.2. […] 22q11.2 syndrome is caused by a genetic mutation change, more commonly now known as a genetic variant. Affected individuals have a fifty percent chance of passing the syndrome on to their offspring. […] This syndrome is autosomal dominant; these are the genes known to be involved: TBX1, ARVCF, GP1BB, UFD1L, HIRA, COMT, JMJD1C, RREB1, SEC24C.

• #1 DiGeorge (22q11.2 deletion) syndrome: Clinical features and diagnosis – UpToDate

  https://www.uptodate.com/contents/digeorge-22q11-2-deletion-syndrome-clinical-features-and-diagnosis

  DiGeorge syndrome (DGS) is a constellation of signs and symptoms associated with defective development of the pharyngeal pouch system. Most cases are caused by a heterozygous chromosomal deletion at 22q11.2. Chromosome 22q11.2 deletion syndrome (22qDS) includes DGS and other similar syndromes, such as velocardiofacial syndrome. […] Thymic defects in DGS result in a range of T cell deficits. Most patients with DGS have mild defects in T cell numbers and are not severely immunodeficient. Approximately 1 percent, however, have a complete absence of thymic tissue and profound immunodeficiency. This form of DGS, called complete DGS, is a type of congenital athymia with a severe combined immunodeficiency (SCID) phenotype and is life threatening if not corrected with immune reconstitution by thymic tissue implantation or potentially hematopoietic cell transplantation in some instances.

• #1 DiGeorge Syndrome: a not so rare disease | Clinics

  https://www.elsevier.es/en-revista-clinics-22-articulo-digeorge-syndrome-not-so-rare-S1807593222029477

  The DiGeorge Syndrome was first described in 1968 as a primary immunodeficiency resulting from the abnormal development of the third and fourth pharyngeal pouches during embryonic life. It is characterized by hypocalcemia due to hypoparathyroidism, heart defects, and thymic hypoplasia or aplasia. Its incidence is 1:3000 live births and, despite its high frequency, little is known about its natural history and progression. This is probably due to diagnostic difficulties and the great variety of names used to describe it, such as velocardiofacial, Shprintzen, DiGeorge, and CATCH 22 Syndromes, as well as conotruncal facial anomaly. All represent the same genetic condition, chromosome 22q11.2 deletion, which might have several clinical expressions. […] In spite of the high frequency of DiGeorge Syndrome (DGS), the commonest chromosome deletion syndrome, its diagnosis is often not suspected. Variable clinical phenotypes and different abnormalities may be caused by 22q11.2 deletion: thymus dysfunction, cardiac diseases, immunodeficiency, and other clinical problems.

• #1 DiGeorge Syndrome: a not so rare disease | Clinics

  https://www.elsevier.es/en-revista-clinics-22-articulo-digeorge-syndrome-not-so-rare-S1807593222029477

  Most DGS patients are hemizygous for a 3Mb region on human chromosome 22 while others have a smaller 1.5Mb nested deletion. These observations suggest that haploinsufficiency of one or more genes on human chromosome 22 are responsible for its etiology. […] The 22q11.2 deletion is the most common human chromosome deletion, and its incidence is about 1:3000 live births. […] The frequency of cardiac malformations in patients with DGS ranges from 49% to 83%. Conotruncal defects are the most commonly-seen heart diseases, which suggests that patients may have the tetralogy of Fallot. […] The 22q11.2 deletion should be investigated in all patients with heart malformations, such as tetralogy of Fallot, disrupted aortic arch, septal defects, and truncus arteriosus. […] Diagnosis becomes more difficult when a patient with classic features of velocardiofacial syndrome or DGS has no evidence of deletion by FISH. A point mutation, which has been described in a few patients, might be present in T-box 1 (TBX1).

• #1

  https://link.springer.com/article/10.1007/s40618-023-02276-0

  Patients with the 22q11.2 deletion syndrome (22q11DS) frequently display cardiological and psychiatric diseases, but are also at increased risk for endocrine manifestations. […] The most frequent endocrine manifestation associated with 22q11DS is hypocalcaemia due to hypoparathyroidism. […] Hypoparathyroidism is considered the most important cause of hypocalcaemia in 22q11DS and is secondary to congenital parathyroid aplasia/hypoplasia. […] Besides hypoparathyroidism, an increased prevalence of functional and structural thyroid diseases has been observed. […] The higher prevalence of thyroid disorders reported in patients with 22q11 DS mainly concerns a higher prevalence of primary hypothyroidism. […] The prevalence of hypothyroidism agrees with previous studies with prevalence ranging between 20 and 30%.

• #1 DiGeorge Syndrome immune disorder | Children’s Wisconsin

  https://childrenswi.org/medical-care/immune-deficiency/immune-disorders/digeorge-syndrome

  Approximately 10 percent of individuals who have the features velo-cardio-facial syndrome (VCFS) do not have a deletion in the chromosome 22q11 region. Other chromosome defects have been associated with these features, as have maternal diabetes, fetal alcohol syndrome, and prenatal exposure to Accutane (a medication for cystic acne).

• #1 DiGeorge syndrome – WikiLectures

  https://www.wikilectures.eu/w/DiGeorge_syndrome

  The most common cause of this syndrome is a deletion on the long arm of chromosome 22 (section 22q11), which is present in 90% of patients with DiGeorg’s syndrome. […] The syndrome occurs mostly sporadically, but cases of familial occurrence are also described, where the syndrome showed an autosomal dominant type of inheritance. […] In addition to the 22q11 deletion itself, translocations have also been described – e.g. t (2; 22), t (4; 22) or t (20; 22). […] Characteristic symptoms of this syndrome have also been described for deletions on chromosomes other than the 22q11 region – for example, del (10p13), del (18q21.33) or del (4q21.3-q25). […] Due to similar phenotypic manifestations (generally velocardiofacial anomalies) and the same deletion, DiGeorg’s, Shprintzen’s and Taka’s syndrome have recently been classified as CATCH 22 (Cardiac abnormalities /abnormal facies, T cell deficit due to thymic hypoplasia, cleft palate, Hypocalcemia due to hypoparathy resulting from 22q11 deletion).

• #1 22Q11.2 Deletion Syndrome: Common but Underrecognized | Children’s Hospital of Philadelphia

  https://www.chop.edu/news/22q112-deletion-syndrome-common-underrecognized

  A microarray was sent, and a few weeks later revealed a chromosome 22q11.2 deletionthe most common cause of DiGeorge syndrome (DGS), despite his lack of classic triad of DGS: congenital heart disease, hypocalcemia, and immunodeficiency. […] Importantly, the 22q11.2 deletions observed in these patients were identical, providing indisputable evidence for a common etiology across all conditions. […] Today, the term DGS is generally reserved for those rare instances when the etiology is not caused by a 22q11.2 deletion, eg, in association with CHARGE syndrome (due to CHD7 mutations on chromosome 8) and teratogens, such as retinoic acid or diabetic embryopathy. […] 22q11.2DS is quite variable and can present with any combination of congenital anomalies, medical issues, cognitive deficits, behavioral differences, and later onset conditions (see Figure 2)all far extending the original description of DGS. […] Importantly, 22q11.2DS is common. It is the most common cause of syndromic palatal abnormalities and schizophrenia, and the second most common cause of congenital heart disease and developmental delay after Down syndrome.

• #1 DiGeorge syndrome – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/947

  DiGeorge syndrome (also known as 22q11.2 deletion syndrome) predominantly results from a microdeletion in chromosome 22, which disrupts the development of the pharyngeal arches and pouches, and may also cause neurological, immunological, endocrinological, or cognitive deficits. […] The deletion causes a reduction in TBX1, a key transcription factor for development of the pharyngeal arches. […] This developmental disruption may cause cardiac anomalies, immunological abnormalities, cleft lip and palate, hypoparathyroidism, learning disabilities, and schizophrenia. […] The disorder is notable for marked variation in the penetrance of the various features.

• #1 22q11.2 Deletion Syndrome (DiGeorge Syndrome) | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/22q112-deletion-syndrome

  22q11.2 deletion syndrome is a genetic condition that causes a combination of medical problems. […] This condition is caused by a missing a part of chromosome 22. The specific area of the chromosome that is missing is 22q11.2. […] About 10 to 15 percent of cases are inherited. A parent with 22q11.2 deletion has a 50 percent chance of passing it on to each of their children. […] Its estimated that about 1 in 4,000 children are born with 22q11.2 deletion syndrome, however it may actually be more common since mild cases may go undiagnosed. […] In some cases a deletion is not present but there is a change in a gene called TBX1.

• #1 Deletion Syndrome 22q11.2: A Systematic Review

  https://www.mdpi.com/2227-9067/9/8/1168

  22q11.2 deletion syndrome (DS 22q11.2) is a rare disease of genetic origin, caused by the loss of the q11.2 region of chromosome 22. […] This clinical entity, in addition to being called 22q11.2 deletion syndrome, is also known by several other names, such as “DiGeorge syndrome” and “velocardiofacial syndrome.” […] Ninety percent of cases of DiGeorge syndrome are de novo, although some cases of autosomal dominant inheritance (8–28%) have been reported. […] The cause of this syndrome is most often a 3 million base pair deletion in part of chromosome 22, located on the long arm (q) in the q11.2 region. […] In most cases, there are no other cases in the family (de novo) but in about 10% of cases the syndrome is inherited from a parent. […] In addition, deletions in the DiGeorge region may also occur. Some of these include the TBX1 gene, which plays an important role in the development of the heart, parathyroid glands, thymus and facial structure.

• #1 22q11.2 deletion syndrome | MedLink Neurology

  https://www.medlink.com/articles/22q11-2-deletion-syndrome

  To date, no significant correlation exists between the size of the deletion and the severity of the phenotype. […] The embryology of the condition is caused by abnormal development of the third and fourth pharyngeal pouches and the fourth aortic arch. […] DiGeorge and velocardiofacial syndrome studies suggest a role for TBX1 in mediating epithelial-mesenchymal signaling in regions of the developing face of the mouse.

• #1 DiGeorge Syndrome (22q11.2 Deletion): Signs, Diagnosis, and Treatment

  https://resources.healthgrades.com/right-care/symptoms-and-conditions/digeorge-syndrome

  Most people with DiGeorge syndrome have about 3 million DNA base pair deletions on one copy of chromosome 22. Some people have smaller deletions. All of this contributes to the variation in symptoms and severity. […] However, one gene, TBX1, seems to be responsible for a subset of the symptoms of the disorder. These include facial feature differences, heart defects, hearing loss, and cleft palate. […] In most cases, 22q11.2 deletion syndrome is not inherited. Instead, the egg or sperm that led to the pregnancy had the chromosome deletion. This can happen by chance during egg or sperm production. About 90% of people with DiGeorge syndrome acquire the deletion this way. The other 10% of people inherit the chromosome 22q deletion from a parent. […] The pattern of inheritance is autosomal dominant. You have two copies of chromosome 22 in each cell — one from each parent. Autosomal dominant inheritance means that only one copy of chromosome 22, from your mother or your father, needs to have the deletion for you to develop DiGeorge syndrome.

• #1 22q11.2 Deletion and Duplication Syndromes | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/22q112-deletion-and-duplication-syndromes

  22q11.2 deletion is the underlying cause of the medical problems associated with DiGeorge syndrome, velocardiofacial syndrome and conotruncal anomaly face syndrome, as well as some of the problems associated with Opitz G/BBB and Cayler cardiofacial syndromes. […] Most cases of 22q 11.2 deletion and duplication syndromes occur at random and aren’t inherited or related to any identifiable cause. However, approximately 5-10 percent of children with a 22q11.2 deletion inherit it from a parent who has a mild — usually undiagnosed — form of the disorder. […] People with a 22q11.2 deletion have a very small piece of chromosome 22 missing; that’s why the disorder is called a „deletion.”

• #1 22q11.2 Deletion Syndrome – MN Dept. of Health

  https://www.health.state.mn.us/diseases/cy/22q112.html

  Several overlapping syndromes are included in the 22q11.2 deletion syndrome. These include: DiGeorge syndrome. Their common genetic cause is a microdeletion (a very small piece of DNA is missing) from the long arm of chromosome 22. This chromosome deletion is the most common deletion in human beings. 22q11.2 Deletion Syndrome is a contiguous gene deletion syndrome. If this section of the DNA is missing, many genes can be missing which usually causes functional and developmental changes for the person who carries it. […] 22q11.2 deletion syndrome is the second most common cause of developmental delay and major congenital heart disease after Down syndrome. […] 22q11.2 deletion syndrome often has a subset of some or all of the following features. […] Hypocalcemia (low levels of calcium in the blood), which occurs in about half of people with a 22q11.2 deletion.

• #1 DiGeorge (22q11.2 deletion) syndrome: Epidemiology and pathogenesis – UpToDate

  https://www.uptodate.com/contents/digeorge-22q11-2-deletion-syndrome-epidemiology-and-pathogenesis

  DiGeorge syndrome (DGS) is a constellation of signs and symptoms associated with defective development of the pharyngeal pouch system. Most cases are caused by a heterozygous chromosomal deletion at 22q11.2 (22q11.2 deletion syndrome [22qDS]); deletions in this chromosome are seen in other patients with similar syndromes, such as velocardiofacial syndrome (VCFS; also called Shprintzen syndrome). […] A large population-based study in the United States designed to ascertain the prevalence, phenotype, and incidence of cardiac disease revealed that heterozygous chromosome 22q11.2 deletions are relatively common in the general population, making 22qDS the most prevalent microdeletion syndrome. This study found that 1 in 5950 live-births had a deletion in this chromosomal area, and, within this subset of infants, 83 percent had an associated cardiac defect. Another population-based study reported that the incidence of 22qDS was as high as 1 in 4000 live-births. Two multicenter studies aimed at prenatal population-based genetic screening found that the incidence for 22qDS was considerably higher than postnatal population-based studies, with prevalences as high as approximately 1 in 400 to 1000 fetuses in low-risk pregnancies.

• #1 DiGeorge Syndrome: Causes, Risk Factors, Screening and Prevalence – London Pregnancy Clinic

  https://www.londonpregnancy.com/digeorge-syndrome-causes-risk-factors-screening-and-prevalence/

  DiGeorge Syndrome, also commonly known as 22q11.2 deletion syndrome (or simply 22q del,) is a complex and multifaceted disorder that many people may not be aware of. […] DiGeorge Syndrome is a chromosomal disorder caused by the deletion of a small piece of chromosome 22, specifically on the q11.2 region. The deletion happens spontaneously during the formation of reproductive cells or in early fetal development. The primary cause of 22q del is unknown, and it typically isnt inherited from the parents. […] Although the exact cause of the chromosomal deletion leading to DiGeorge Syndrome is unknown, its not typically associated with the age of the parent, unlike some other genetic disorders. The occurrence appears to be mostly random, which means that all pregnancies, irrespective of familial history, have a minimal but real risk. […] DiGeorge Syndrome is considered one of the most common genetic syndromes, second only to Downs Syndrome. In the general population, its estimated to affect between 1 in 2,000 to 1 in 4,000 live births. Younger women have the same chance to deliver baby with 22q del as older ones.

• #1 DiGeorge Syndrome immune disorder | Children’s Wisconsin

  https://childrenswi.org/medical-care/immune-deficiency/immune-disorders/digeorge-syndrome

  As mentioned, 90 percent of patients with the features of this syndrome are missing a small part of their chromosome 22 at the q11 region. This region encompasses about 30 individual genes and results in developmental defects in specific structures throughout the body. […] It is not known why this region of chromosome 22 is prone to become deleted, but this is one of the most frequent chromosome defects in newborns. Deletion 22q11 is estimated to occur in one in 3,000 to 4,000 live births. Most of the 22q11 deletion cases are new occurrences or sporadic (occurs by chance). However, in about 10 percent of families, the deletion is inherited and other family members are affected or at risk for passing this deletion to their children. The gene is autosomal dominant, therefore, any person who has this deletion has a 50 percent chance of passing the deletion to a child.

• #1 DiGeorge (22q11.2 deletion) syndrome: Clinical features and diagnosis – UpToDate

  https://www.uptodate.com/contents/digeorge-22q11-2-deletion-syndrome-clinical-features-and-diagnosis

  Use of the term 22q11.2 deletion syndrome (22qDS) is preferred for patients with this genetic defect and a DGS phenotype, with the term DiGeorge syndrome (DGS) reserved for patients who have phenotypic features consistent with DGS but do not have a 22q11.2 deletion (they may have a different pathogenic variant associated with the syndrome or no identified genetic defect).

• #2 22q11.2 deletion syndrome | MedLink Neurology

  https://www.medlink.com/articles/22q11-2-deletion-syndrome

  DiGeorge and velocardiofacial syndrome (22q11.2 deletion syndrome) is the most common microdeletion disorder in humans and, hence, one of the most common multiple malformation syndromes, with an estimated prevalence of 1 in 2000 to 1 in 4000. […] The initial evidence for involvement of genes on chromosome 22 in the etiology of DiGeorge syndrome included a family with a chromosome 2;22 translocation. Family members with an unbalanced rearrangement that resulted in monosomy 22q11.2 had clinical features of DiGeorge syndrome. […] Approximately 76% of individuals to 90% of individuals with DiGeorge and velocardiofacial syndrome have a chromosome 22q11.2 microdeletion recognizable by fluorescence in-situ hybridization. […] The typically deleted region is subdivided into five intervals, encompassing some 50 genes.

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

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

  DiGeorge syndrome (DGS) is one of a group of phenotypically similar disorders including velocardiofacial syndrome (VCFS, or Shprintzen syndrome) and conotruncal anomaly face (CTAF) syndrome that share a microdeletion of chromosome 22q11.2, a region known as the DGS critical region. […] The syndrome is caused by a microdeletion of band 22q11.2. The long arm of chromosome 22 (at q11) is prone to a microdeletion because of the presence of eight nonallelic, flanking, low-copy repeat DNA sequence clusters (LCR22) labeled AH. […] The most common deletion present in 85% of individuals is 3 million base pair (Mb) in size, extends from A to D, and encompasses approximately 40 genes and 4 micro RNAs. […] Among other genes mapped in the deleted region that have been implicated in the pathogenesis of 22q11.2DS include HIRA and UFD1L.

• #2 22q11.2 Deletion Syndrome – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1523/

  22q11.2DS is an autosomal dominant contiguous gene deletion syndrome. […] In 22q11.2DS caused by a 3.0 (2.54)-Mb deletion, the deletion is de novo in more than 90% of individuals and inherited from a heterozygous parent in about 10% of individuals. […] The proportion of individuals with a nested deletion (i.e., a recurrent, atypical shorter deleted segment [LCR22B-D] nested within the large typically deleted region) inherited from an affected parent is higher (60%). […] The term DiGeorge syndrome is now reserved for individuals who have clinical features of 22q11.2DS but do not have an identified 22q11.2 deletion.

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

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

  DiGeorge syndrome is a genetic condition caused by a missing piece of chromosome 22. Another name for DiGeorge syndrome is 22q11.2 deletion syndrome. […] DiGeorge syndrome (22q11.2 deletion syndrome) can affect anyone since 90% of cases occur as a result of a random deletion on chromosome 22. This happens when the egg and sperm meet in the early stages of fetal development. The rate of occurrence is unpredictable. This condition isnt caused by something the parents did before or during pregnancy. […] A missing part of chromosome 22 causes DiGeorge syndrome (22q11.2 deletion syndrome). Each chromosome holds thousands of genes. Genes are responsible for providing the instruction manual to help your body grow and function. The term 22q11.2 gives the specific location on the chromosome where genes are missing; segment 11 on the long arm (q) of chromosome 22. When youre missing potentially thousands of genes, your body doesnt have the instructions you need to develop as expected and youll experience symptoms.

• #2 DiGeorge syndrome (22q11 deletion)

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

  DiGeorge syndrome is caused by a problem with a person’s genes, called 22q11 deletion. […] DiGeorge syndrome is caused by a problem called 22q11 deletion. This is where a small piece of genetic material is missing from a person’s DNA. […] In about 9 in 10 cases (90%), the bit of DNA was missing from the egg or sperm that led to the pregnancy. […] In around 1 in 10 cases (10%), the 22q11 deletion is passed on to a child by a parent who has DiGeorge syndrome, although they may not realise they have it if it’s mild.

• #2 DiGeorge Syndrome (22q11.2 Deletion): Signs, Diagnosis, and Treatment

  https://resources.healthgrades.com/right-care/symptoms-and-conditions/digeorge-syndrome

  Most people with DiGeorge syndrome have about 3 million DNA base pair deletions on one copy of chromosome 22. Some people have smaller deletions. All of this contributes to the variation in symptoms and severity. […] However, one gene, TBX1, seems to be responsible for a subset of the symptoms of the disorder. These include facial feature differences, heart defects, hearing loss, and cleft palate. […] In most cases, 22q11.2 deletion syndrome is not inherited. Instead, the egg or sperm that led to the pregnancy had the chromosome deletion. This can happen by chance during egg or sperm production. About 90% of people with DiGeorge syndrome acquire the deletion this way. The other 10% of people inherit the chromosome 22q deletion from a parent. […] The pattern of inheritance is autosomal dominant. You have two copies of chromosome 22 in each cell — one from each parent. Autosomal dominant inheritance means that only one copy of chromosome 22, from your mother or your father, needs to have the deletion for you to develop DiGeorge syndrome.

• #2 22q11 deletion syndrome: Genetics

  https://www.aboutkidshealth.ca/22q11-deletion-syndrome-genetics

  22q11DS is known by many names such as velo-cardio-facial syndrome and DiGeorge syndrome. […] 22q11DS is a genetic disorder. It results from a small missing piece of genetic material (DNA) on chromosome 22. This is called a deletion. […] The 22q11 deletion happens most of the time by chance. In some families, the 22q11 deletion can be inherited from a parent. […] 22q11DS is caused by a deletion in chromosome 22. A person will have 22q11DS if one chromosome 22 in the pair has the deletion. […] In some people with 22q11DS (about 10%), the deletion is inherited from a parent. […] Most of the time, 22q11DS is the result of a new genetic deletion that occurs when a baby is conceived. This is called a de novo deletion and occurs by chance in either the moms egg or the dads sperm. […] A de novo deletion is not caused by anything the parents did before or during the pregnancy. […] A person who has 22q11DS has a 50% chance (1 in 2) of having a child with 22q11DS.

• #2 22q11.2 Deletion Disorders (DiGeorge Syndrome and Velo-Cardio-Facial Syndrome) | American Heart Association

  https://www.heart.org/en/health-topics/congenital-heart-defects/about-congenital-heart-defects/22q112-deletion-disorders-digeorge-syndrome-and-velocardiofacial-syndrome

  22q11.2 deletion syndrome (also known as DiGeorge syndrome and velo-cardio-facial syndrome) is a disorder caused by the deletion of a small piece of chromosome 22. 22q11.2 identifies the specific chromosomal location where there is a microdeletion. […] 22q11.2 deletion syndrome affects an estimated 1 in 4,000 to 1 per 7,000 births. Most children with a 22q11.2 deletion are the first person in their family to have that problem as a result of a random event during pregnancy. Affected people may pass the syndrome to their children so it’s helpful to test the parents. […] When someone with a 22q11.2 deletion has children of their own, there is a 50-50 chance of passing along a copy of chromosome 22 with that deletion with each pregnancy. This also means, of course, that there is an equal chance that the next child will not inherit the deletion.

• #2 22q11.2 deletion syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/22q112-deletion-syndrome/

  22q11.2 deletion syndrome is a disorder caused by the deletion of a small piece of chromosome 22. […] Most people with 22q11.2 deletion syndrome are missing a sequence of about 3 million DNA building blocks (base pairs) on one copy of chromosome 22 in each cell. This region contains 30 to 40 genes, many of which have not been well characterized. […] Researchers are working to identify all of the genes that contribute to the features of 22q11.2 deletion syndrome. They have determined that the loss of a particular gene on chromosome 22, TBX1, is probably responsible for many of the syndrome’s characteristic signs (such as heart defects, a cleft palate, distinctive facial features, hearing loss, and low calcium levels). […] The inheritance of 22q11.2 deletion syndrome is considered autosomal dominant because a deletion in one copy of chromosome 22 in each cell is sufficient to cause the condition.

• #2

  https://omim.org/entry/188400

  A number sign (#) is used with this entry because DiGeorge syndrome is caused by a 1.5- to 3.0-Mb heterozygous deletion of chromosome 22q11.2. Haploinsufficiency of the TBX1 gene (602054) in particular is responsible for most of the physical malformations. There is evidence that point mutations in the TBX1 gene can also cause the disorder. […] Most cases result from a deletion of chromosome 22q11.2 (the DiGeorge syndrome chromosome region, or DGCR). Several genes are lost including the putative transcription factor TUPLE1 which is expressed in the appropriate distribution. […] A collective acronym CATCH22 has been proposed for these differing presentations. […] DiGeorge syndrome is usually sporadic and results from de novo deletion within chromosome 22. […] The first dominant pedigree in which marked clinical variability was associated with dominant transmission of a 22q11 deletion was reported by Wilson et al. (1991); the mother had the typical dysmorphic features.

• #2 DiGeorge Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549798/

  DiGeorge syndrome (DGS) is a congenital disorder with a broad phenotypic presentation, which results predominantly from the microdeletion of chromosome 22 at a location known as 22q11.2. […] About 90% of DGS cases are a result of a deletion in chromosome 22, more specifically on the long arm (q) at the 11.2 locus (22q11.2). Most of these mutations arise de novo with no genetic abnormalities noted in the genome of the parents of children with DGS. […] Researchers have identified over 90 different genes at this locus, some of which they have studied in mouse models. The most studied of these genes is T-box transcription factor 1 (TBX1), which correlates with severe defects in the development of the heart, thymus, and parathyroid glands of mouse models. TBX1 also correlates with neuromicrovascular anomalies, which may be responsible for the behavioral and developmental abnormalities seen in DGS.

• #2 DiGeorge or 22q11.2 deletion syndrome | Immune Deficiency Foundation

  https://primaryimmune.org/understanding-primary-immunodeficiency/types-of-pi/digeorge-or-22q112-deletion-syndrome

  DiGeorge syndrome, most frequently caused by a deletion at 22q11.2, is a PI caused by abnormal migration and development of certain cells and tissues during fetal development. […] DGS most commonly occurs in children with 22q11.2 deletion syndrome, CHARGE syndrome, and infants of diabetic mothers. […] The most common cause is due to a genetic defect called 22q11.2 deletion syndrome (22q11.2DS). In children with 22q11.2DS, a piece of chromosome 22 is missing. […] Most cases of 22q11.2 DS occur spontaneously. DGS is caused by a large deletion from chromosome 22. This deletion means that several genes from this region are not present in those with DGS. […] Many of the manifestations of DGS have been linked to deletion of the T-box transcription factor 1 (TBX1) gene on chromosome 22q11, which plays a role in neural crest cell migration, pharyngeal arch (PA) development, and formation of the pharyngeal pouches.

• #2 22q11.2 Deletion Syndrome (DiGeorge Syndrome) | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/22q112-deletion-syndrome

  22q11.2 deletion syndrome is a genetic condition that causes a combination of medical problems. […] This condition is caused by a missing a part of chromosome 22. The specific area of the chromosome that is missing is 22q11.2. […] About 10 to 15 percent of cases are inherited. A parent with 22q11.2 deletion has a 50 percent chance of passing it on to each of their children. […] Its estimated that about 1 in 4,000 children are born with 22q11.2 deletion syndrome, however it may actually be more common since mild cases may go undiagnosed. […] In some cases a deletion is not present but there is a change in a gene called TBX1.

• #2 22q11.2 deletion syndrome | MedLink Neurology

  https://www.medlink.com/articles/22q11-2-deletion-syndrome

  To date, no significant correlation exists between the size of the deletion and the severity of the phenotype. […] The embryology of the condition is caused by abnormal development of the third and fourth pharyngeal pouches and the fourth aortic arch. […] DiGeorge and velocardiofacial syndrome studies suggest a role for TBX1 in mediating epithelial-mesenchymal signaling in regions of the developing face of the mouse.

• #2 Immunodeficiency Search

  https://www.immunodeficiencysearch.com/22q11-2-deletion-syndrome

  The deletion results in impaired embryogenesis of the 3rd and 4th pharyngeal pouches. These structures give rise to thymus (which is essential for T-cell development) and the parathyroid (the absence of which causes hypocalcemia). […] Patients have an increased risk for developing autoimmune conditions. A decrease in the percentage of CD4+CD25+ T-regulatory cells has been observed in patients with DGS compared to normal controls.

• #2 DiGeorge Syndrome: a not so rare disease | Clinics

  https://www.elsevier.es/en-revista-clinics-22-articulo-digeorge-syndrome-not-so-rare-S1807593222029477

  Most DGS patients are hemizygous for a 3Mb region on human chromosome 22 while others have a smaller 1.5Mb nested deletion. These observations suggest that haploinsufficiency of one or more genes on human chromosome 22 are responsible for its etiology. […] The 22q11.2 deletion is the most common human chromosome deletion, and its incidence is about 1:3000 live births. […] The frequency of cardiac malformations in patients with DGS ranges from 49% to 83%. Conotruncal defects are the most commonly-seen heart diseases, which suggests that patients may have the tetralogy of Fallot. […] The 22q11.2 deletion should be investigated in all patients with heart malformations, such as tetralogy of Fallot, disrupted aortic arch, septal defects, and truncus arteriosus. […] Diagnosis becomes more difficult when a patient with classic features of velocardiofacial syndrome or DGS has no evidence of deletion by FISH. A point mutation, which has been described in a few patients, might be present in T-box 1 (TBX1).

• #2 DiGeorge Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549798/

  DGS results from microdeletion of 22q11.2, which encodes over 90 genes. Patients with DGS display a broad array of phenotypes, and the most common findings include cardiac anomalies, hypocalcemia, and hypoplastic thymus. […] On a genetic basis, TBX1 has correlations with the most prominent phenotypes characteristic of DGS. Failure in embryologic development of the pharyngeal pouches, which is driven by TBX1, leads to absence or hypoplasia of the thymus and parathyroid glands. […] A 22q11.2 knockout mouse model has also been studied, with findings pertinent for molecular and behavioral changes seen in Parkinson’s disease, autism spectrum disorder, attention deficit hyperactivity disorder, and schizophrenia. […] These findings, as well as the neuromicrovascular pathology found in TBX1 knockout mice, suggest a molecular basis for the psychiatric pathologies associated with DGS.

• #2 DiGeorge syndrome

  https://dermnetnz.org/topics/digeorge-syndrome

  DiGeorge syndrome is caused by dysfunctional development of certain cells and tissues in utero. Approximately 90% of the patients with DiGeorge syndrome have a deletion of a segment of 3040 genes on chromosome 22. Generally, this is considered to be the consequence of a random event in either the egg or the sperm, but more rarely it can be passed on from parent to child. […] DiGeorge syndrome is due to chromosomal defects that arise early in gestation.

• #2 DiGeorge (22q11.2 deletion) syndrome: Clinical features and diagnosis – UpToDate

  https://www.uptodate.com/contents/digeorge-22q11-2-deletion-syndrome-clinical-features-and-diagnosis

  DiGeorge syndrome (DGS) is a constellation of signs and symptoms associated with defective development of the pharyngeal pouch system. Most cases are caused by a heterozygous chromosomal deletion at 22q11.2. Chromosome 22q11.2 deletion syndrome (22qDS) includes DGS and other similar syndromes, such as velocardiofacial syndrome. […] Thymic defects in DGS result in a range of T cell deficits. Most patients with DGS have mild defects in T cell numbers and are not severely immunodeficient. Approximately 1 percent, however, have a complete absence of thymic tissue and profound immunodeficiency. This form of DGS, called complete DGS, is a type of congenital athymia with a severe combined immunodeficiency (SCID) phenotype and is life threatening if not corrected with immune reconstitution by thymic tissue implantation or potentially hematopoietic cell transplantation in some instances.

• #2 Immunodeficiency Search

  https://www.immunodeficiencysearch.com/22q11-2-deletion-syndrome

  A hemizygous deletion of chromosome 22q11.2 can result in a spectrum of clinical disease including velocardiofacial syndrome (VCFS) and DiGeorge syndrome (DGS). […] Although the most common deletion includes a region containing more than 35 genes, the TBX1 gene has emerged as one of the most likely causes of the DGS phenotype. […] The classic triad for DGS includes cardiac anomalies, hypocalcemia, and hypoplastic thymus leading to T-cell immune dysfunction. Approximately 90% of patients with DGS have the 22q11.2 deletion. […] Up to 80% of patients with 22q11.2 deletion will have decreased T-cell numbers as a result of thymic hypoplasia. […] The most commonly deleted region of chromosome 22q11.2 includes more than 35 genes. TBX1 has emerged as the most likely gene contributing to the cardiac, thymic, and parathyroid abnormalities.

• #2

  https://link.springer.com/article/10.1007/s40618-023-02276-0

  The presence of metabolic complications is shown in Table 4. […] Hypoparathyroidism, hypothyroidism, and obesity are common endocrinological manifestations in patients with 22q11DS. However, hypoparathyroidism is probably frequently underdiagnosed and undertreated. […] Screening for endocrine manifestations in the 22q11DS is proposed by international guidelines, but adherence to these guidelines is rather low.

• #2 DIGEORGE SYNDROME (22q11.2)

  https://medicover-genetics.com/product/digeorge-syndrome/

  DiGeorge syndrome represents a part of the highly variable clinical spectrum of microdeletion 22q11.2. It is caused by a developmental defect of the third and fourth pharyngeal pouches or derived structures such as the thymus and parathyroid glands and the fourth-gill arch. […] In about 5 to 10% of cases, microdeletion 22q11.2 is inherited from one parent. […] The small deletion on the long arm (q) of chromosome 22 causes a syndrome with a diverse collection of symptoms. […] 22q11.2 deletion syndrome has a prevalence of 1 in 2,000 that is thought to be an underestimate due to the lack of syndrome familiarity and recognition by doctors, and the wide variability of symptoms. […] The deleted region is thought to contain 30-40 genes but could contain nearly 90 genes. […] About 90% of 22q11.2 cases occur sporadically without any hereditary risk factor. […] Individuals affected by the 22q11.2 deletion usually have difficulty with verbal memory and visual-spatial skills, language, and reading comprehension, along with limited social and emotional function. […] 22q11.2 is also the strongest known genetic risk factor for schizophrenia.

• #2 DiGeorge (22q11.2 deletion) syndrome: Clinical features and diagnosis – UpToDate

  https://www.uptodate.com/contents/digeorge-22q11-2-deletion-syndrome-clinical-features-and-diagnosis

  Use of the term 22q11.2 deletion syndrome (22qDS) is preferred for patients with this genetic defect and a DGS phenotype, with the term DiGeorge syndrome (DGS) reserved for patients who have phenotypic features consistent with DGS but do not have a 22q11.2 deletion (they may have a different pathogenic variant associated with the syndrome or no identified genetic defect).

• #2 DiGeorge Syndrome (DGS) – Birth Defect Fact Sheet

  https://birthdefects.org/digeorge-syndrome/

  DiGeorge Syndrome (DGS), also referred to as Velo-Cardio-Facial Syndrome (VCFS), is an immunodeficiency disorder characterized by various congenital abnormalities. […] Ninety percent of individuals with DGS are missing a piece of genetic information on chromosome 22 at the q11 region, referred to as a deletion on chromosome 22. Most of the 22q11 deletions are new occurrences or sporadic. About 6-10% of the deletions are inherited. The gene is autosomal dominant, meaning each child born to a person with the gene has a 50% chance of receiving the gene and manifesting the syndrome. […] The remaining 10% of individuals with DGS do not have a deletion in the chromosome 22q11 region. These cases have been associated with fetal alcohol syndrome, maternal diabetes, prenatal exposure to Accutane, and other chromosome defects.

• #2 22Q11.2 Deletion Syndrome: Common but Underrecognized | Children’s Hospital of Philadelphia

  https://www.chop.edu/news/22q112-deletion-syndrome-common-underrecognized

  A microarray was sent, and a few weeks later revealed a chromosome 22q11.2 deletionthe most common cause of DiGeorge syndrome (DGS), despite his lack of classic triad of DGS: congenital heart disease, hypocalcemia, and immunodeficiency. […] Importantly, the 22q11.2 deletions observed in these patients were identical, providing indisputable evidence for a common etiology across all conditions. […] Today, the term DGS is generally reserved for those rare instances when the etiology is not caused by a 22q11.2 deletion, eg, in association with CHARGE syndrome (due to CHD7 mutations on chromosome 8) and teratogens, such as retinoic acid or diabetic embryopathy. […] 22q11.2DS is quite variable and can present with any combination of congenital anomalies, medical issues, cognitive deficits, behavioral differences, and later onset conditions (see Figure 2)all far extending the original description of DGS. […] Importantly, 22q11.2DS is common. It is the most common cause of syndromic palatal abnormalities and schizophrenia, and the second most common cause of congenital heart disease and developmental delay after Down syndrome.

• #2 DiGeorge Syndrome: a not so rare disease | Clinics

  https://www.elsevier.es/en-revista-clinics-22-articulo-digeorge-syndrome-not-so-rare-S1807593222029477

  The DiGeorge Syndrome was first described in 1968 as a primary immunodeficiency resulting from the abnormal development of the third and fourth pharyngeal pouches during embryonic life. It is characterized by hypocalcemia due to hypoparathyroidism, heart defects, and thymic hypoplasia or aplasia. Its incidence is 1:3000 live births and, despite its high frequency, little is known about its natural history and progression. This is probably due to diagnostic difficulties and the great variety of names used to describe it, such as velocardiofacial, Shprintzen, DiGeorge, and CATCH 22 Syndromes, as well as conotruncal facial anomaly. All represent the same genetic condition, chromosome 22q11.2 deletion, which might have several clinical expressions. […] In spite of the high frequency of DiGeorge Syndrome (DGS), the commonest chromosome deletion syndrome, its diagnosis is often not suspected. Variable clinical phenotypes and different abnormalities may be caused by 22q11.2 deletion: thymus dysfunction, cardiac diseases, immunodeficiency, and other clinical problems.

• #2 Orphanet: 22q11.2 deletion syndrome

  https://www.orpha.net/en/disease/detail/567

  A rare chromosomal anomaly which causes a congenital malformation disorder that is typically characterized by cardiac defects, palatal anomalies, facial dysmorphism, developmental delay and immune deficiency. […] In most cases, the syndrome is due to a 3 million base pair (Mb) deletion on the chromosomal region 22q11.2 that is flanked by low copy number repeats. The deletion is due to a non-allelic meiotic recombination during spermatogenesis or oogenesis. […] In ~15% of cases, the deletion is nested within the 3 Mb DiGeorge critical region and varies in size. Most deletions include the TBX1 gene that has been shown to be implicated in cardiac, parathyroid, thymus and facial structure development. The variable expression of the 22q11.2 phenotype is thought to be due to genetic modifiers on either the other 22q11.2 allele or on other chromosomes.

• #2 DiGeorge syndrome – WikiLectures

  https://www.wikilectures.eu/w/DiGeorge_syndrome

  The most common cause of this syndrome is a deletion on the long arm of chromosome 22 (section 22q11), which is present in 90% of patients with DiGeorg’s syndrome. […] The syndrome occurs mostly sporadically, but cases of familial occurrence are also described, where the syndrome showed an autosomal dominant type of inheritance. […] In addition to the 22q11 deletion itself, translocations have also been described – e.g. t (2; 22), t (4; 22) or t (20; 22). […] Characteristic symptoms of this syndrome have also been described for deletions on chromosomes other than the 22q11 region – for example, del (10p13), del (18q21.33) or del (4q21.3-q25). […] Due to similar phenotypic manifestations (generally velocardiofacial anomalies) and the same deletion, DiGeorg’s, Shprintzen’s and Taka’s syndrome have recently been classified as CATCH 22 (Cardiac abnormalities /abnormal facies, T cell deficit due to thymic hypoplasia, cleft palate, Hypocalcemia due to hypoparathy resulting from 22q11 deletion).

• #2 DiGeorge (22q11.2 deletion) syndrome: Epidemiology and pathogenesis – UpToDate

  https://www.uptodate.com/contents/digeorge-22q11-2-deletion-syndrome-epidemiology-and-pathogenesis

  DiGeorge syndrome (DGS) is a constellation of signs and symptoms associated with defective development of the pharyngeal pouch system. Most cases are caused by a heterozygous chromosomal deletion at 22q11.2 (22q11.2 deletion syndrome [22qDS]); deletions in this chromosome are seen in other patients with similar syndromes, such as velocardiofacial syndrome (VCFS; also called Shprintzen syndrome). […] A large population-based study in the United States designed to ascertain the prevalence, phenotype, and incidence of cardiac disease revealed that heterozygous chromosome 22q11.2 deletions are relatively common in the general population, making 22qDS the most prevalent microdeletion syndrome. This study found that 1 in 5950 live-births had a deletion in this chromosomal area, and, within this subset of infants, 83 percent had an associated cardiac defect. Another population-based study reported that the incidence of 22qDS was as high as 1 in 4000 live-births. Two multicenter studies aimed at prenatal population-based genetic screening found that the incidence for 22qDS was considerably higher than postnatal population-based studies, with prevalences as high as approximately 1 in 400 to 1000 fetuses in low-risk pregnancies.

• #2 DiGeorge Syndrome: Symptoms, Causes, Diagnosis, and Treatment

  https://www.verywellhealth.com/digeorge-syndrome-overview-4584404

  DiGeorge syndrome, more accurately known as 22q11.2 deletion syndrome, is caused when portions of chromosome 22 (known as genes) are missing. […] Everyone has two copies of chromosome 22, one inherited from each parent. With DiGeorge syndrome, anywhere from 30 to 40 genes will be missing. […] The range and severity of symptoms are largely dependant on the types of genes deleted. […] DiGeorge syndrome is classified as an autosomal dominant disorder, meaning that only one of the two chromosomes need to be affected for symptoms to develop. In around 90% of cases, the deletion will occur spontaneously during the early stages of fetal development. About 10% will be inherited from the genetic material of one parent. […] DiGeorge syndrome is rare, affecting only one of every 4,000 children. The chances of a person with DiGeorge syndrome having an affected child is 50% for each pregnancy.

• #3 22q11.2 Deletion Syndrome: The Most Common Microdeletion Syndrome

  https://www.natera.com/resource-library/panorama/22q11-2-deletion-syndrome-the-most-common-microdeletion-syndrome/

  22q11.2 deletion syndrome is caused by a microdeletion in a specific region of chromosome 22. The size of the deletion varies and can result in up to 40 missing genes. The number and severity of symptoms depends on the location and size of the deletion. In most cases, 22q11.2 deletion syndrome is not inherited, meaning that in most cases neither parent of an affected child has the syndrome. However, people with 22q11.2 deletion syndrome can have children and pass the syndrome on to them. Most cases occur at random, caused by an error during the formation of a sperm or egg cell. […] Since the condition mostly occurs at random, the baseline risk of 22q11.2 deletion occurring in a pregnancy is low. However, if either parent has the syndrome, the risk of passing it on to a child is 50%.

• #3 DiGeorge syndrome (22q11.2 deletion syndrome) – The Oncofertility Consortium

  https://oncofertility.msu.edu/non-malignant-conditions/digeorge-syndrome-22q11-2-deletion-syndrome/

  DiGeorge syndrome is caused by a 1.5-3 Mb hemizygous deletion of chromosome 22q11.2. […] In a majority of cases of DiGeorge Syndrome, the deletion is mediated by homologous recombination between these low copy number repeats. […] Haploinsufficiency of TBX1 is responsible for major phenotypes that are seen in individuals with DiGeorge syndrome. […] However, the variability of phenotypic features with a deletion of TBX1 suggests that altered interaction with downstream genes and environmental effects also affect the disease presentation. […] As in all microdeletion syndromes, inheritance is autosomal dominant, however most cases of DiGeorge syndrome result from a de novo microdeletion.

• #3 DiGeorge syndrome (22q11 deletion)

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

  DiGeorge syndrome is caused by a problem with a person’s genes, called 22q11 deletion. […] DiGeorge syndrome is caused by a problem called 22q11 deletion. This is where a small piece of genetic material is missing from a person’s DNA. […] In about 9 in 10 cases (90%), the bit of DNA was missing from the egg or sperm that led to the pregnancy. […] In around 1 in 10 cases (10%), the 22q11 deletion is passed on to a child by a parent who has DiGeorge syndrome, although they may not realise they have it if it’s mild.

• #3 22q11.2 Deletion Syndrome in Children – Stanford Medicine Children’s Health

  https://www.stanfordchildrens.org/en/topic/default?id=22q112-deletion-syndrome-in-children-90-P01682

  The 22q11.2 deletion syndrome (22q11.2DS) is a genetic disorder. […] Most children with 22q11.2DS are missing 30 to 40 genes. Researchers dont yet know the exact function of many of these genes. But missing the gene TBX1 on chromosome 22 likely causes the syndrome’s most common physical symptoms. These include heart problems and cleft palate. The loss of another gene (called COMT) may also explain the higher risk for behavior problems and mental illness. […] About 9 in 10 cases of 22q11.2DS happen by chance (randomly). They occur when the egg is fertilized. Or they occur early in a babys growth in the mothers uterus. This means that most children with the disorder have no family history of it. […] But a person with the condition can pass it on to his or her children. About 1 in 10 cases are inherited from the mother or the father. When the condition is inherited, other family members could also be affected. A person who has this chromosome deletion has a 1 in 2 chance of passing the problem to a child. […] A child is more at risk for this disorder if he or she has a parent with the condition or is carrying the faulty chromosome. But most cases occur randomly.

• #3

  https://www.singhealth.com.sg/patient-care/conditions-treatments/22q112-deletion-syndrome

  22q11.2 deletion syndrome (22q11.2DS) is a genetic disorder that can affect many parts of the body, including the heart, immune system and development. […] Most individuals with 22q11.2DS are missing a small part of chromosome 22 known as 22q11.2. […] As a result of this deletion at chromosome 22q11.2, an estimated 40 to 60 genes are missing. […] In 90% of cases, neither parent has the chromosome 22q11.2 deletion. […] 22q11.2DS follows a dominant inheritance pattern. This means that having one chromosome 22 with the deletion can cause features of 22q11.2DS. […] A parent with a chromosome 22q11.2 deletion has a 50% chance of passing it down to their offspring.

• #3 DiGeorge or 22q11.2 deletion syndrome | Immune Deficiency Foundation

  https://primaryimmune.org/understanding-primary-immunodeficiency/types-of-pi/digeorge-or-22q112-deletion-syndrome

  DiGeorge syndrome, most frequently caused by a deletion at 22q11.2, is a PI caused by abnormal migration and development of certain cells and tissues during fetal development. […] DGS most commonly occurs in children with 22q11.2 deletion syndrome, CHARGE syndrome, and infants of diabetic mothers. […] The most common cause is due to a genetic defect called 22q11.2 deletion syndrome (22q11.2DS). In children with 22q11.2DS, a piece of chromosome 22 is missing. […] Most cases of 22q11.2 DS occur spontaneously. DGS is caused by a large deletion from chromosome 22. This deletion means that several genes from this region are not present in those with DGS. […] Many of the manifestations of DGS have been linked to deletion of the T-box transcription factor 1 (TBX1) gene on chromosome 22q11, which plays a role in neural crest cell migration, pharyngeal arch (PA) development, and formation of the pharyngeal pouches.

• #3 DiGeorge syndrome

  https://dermnetnz.org/topics/digeorge-syndrome

  DiGeorge syndrome is caused by dysfunctional development of certain cells and tissues in utero. Approximately 90% of the patients with DiGeorge syndrome have a deletion of a segment of 3040 genes on chromosome 22. Generally, this is considered to be the consequence of a random event in either the egg or the sperm, but more rarely it can be passed on from parent to child. […] DiGeorge syndrome is due to chromosomal defects that arise early in gestation.

• #3 Immunodeficiency Search

  https://www.immunodeficiencysearch.com/22q11-2-deletion-syndrome

  The deletion results in impaired embryogenesis of the 3rd and 4th pharyngeal pouches. These structures give rise to thymus (which is essential for T-cell development) and the parathyroid (the absence of which causes hypocalcemia). […] Patients have an increased risk for developing autoimmune conditions. A decrease in the percentage of CD4+CD25+ T-regulatory cells has been observed in patients with DGS compared to normal controls.

• #3 22q11.2 Deletion Syndrome – MN Dept. of Health

  https://www.health.state.mn.us/diseases/cy/22q112.html

  The number and type of associated features will determine the management for each person with 22q11.2 deletion syndrome. […] Developmental delay is often seen in children with 22q11.2 deletion syndrome, including a delay in language. […] As the child grows, skeletal features such as scoliosis (curvature of the spine) and differences in the shape of the cervical spine may become apparent. […] Children with 22q11.2 deletion syndrome will usually have developmental delays that include both motor and speech and language areas.

• #3 DiGeorge Syndrome (DGS) – Birth Defect Fact Sheet

  https://birthdefects.org/digeorge-syndrome/

  DiGeorge Syndrome (DGS), also referred to as Velo-Cardio-Facial Syndrome (VCFS), is an immunodeficiency disorder characterized by various congenital abnormalities. […] Ninety percent of individuals with DGS are missing a piece of genetic information on chromosome 22 at the q11 region, referred to as a deletion on chromosome 22. Most of the 22q11 deletions are new occurrences or sporadic. About 6-10% of the deletions are inherited. The gene is autosomal dominant, meaning each child born to a person with the gene has a 50% chance of receiving the gene and manifesting the syndrome. […] The remaining 10% of individuals with DGS do not have a deletion in the chromosome 22q11 region. These cases have been associated with fetal alcohol syndrome, maternal diabetes, prenatal exposure to Accutane, and other chromosome defects.

• #3 DiGeorge syndrome – WikiLectures

  https://www.wikilectures.eu/w/DiGeorge_syndrome

  The most common cause of this syndrome is a deletion on the long arm of chromosome 22 (section 22q11), which is present in 90% of patients with DiGeorg’s syndrome. […] The syndrome occurs mostly sporadically, but cases of familial occurrence are also described, where the syndrome showed an autosomal dominant type of inheritance. […] In addition to the 22q11 deletion itself, translocations have also been described – e.g. t (2; 22), t (4; 22) or t (20; 22). […] Characteristic symptoms of this syndrome have also been described for deletions on chromosomes other than the 22q11 region – for example, del (10p13), del (18q21.33) or del (4q21.3-q25). […] Due to similar phenotypic manifestations (generally velocardiofacial anomalies) and the same deletion, DiGeorg’s, Shprintzen’s and Taka’s syndrome have recently been classified as CATCH 22 (Cardiac abnormalities /abnormal facies, T cell deficit due to thymic hypoplasia, cleft palate, Hypocalcemia due to hypoparathy resulting from 22q11 deletion).

• #3 DiGeorge Syndrome: Causes, Risk Factors, Screening and Prevalence – London Pregnancy Clinic

  https://www.londonpregnancy.com/digeorge-syndrome-causes-risk-factors-screening-and-prevalence/

  DiGeorge Syndrome, also commonly known as 22q11.2 deletion syndrome (or simply 22q del,) is a complex and multifaceted disorder that many people may not be aware of. […] DiGeorge Syndrome is a chromosomal disorder caused by the deletion of a small piece of chromosome 22, specifically on the q11.2 region. The deletion happens spontaneously during the formation of reproductive cells or in early fetal development. The primary cause of 22q del is unknown, and it typically isnt inherited from the parents. […] Although the exact cause of the chromosomal deletion leading to DiGeorge Syndrome is unknown, its not typically associated with the age of the parent, unlike some other genetic disorders. The occurrence appears to be mostly random, which means that all pregnancies, irrespective of familial history, have a minimal but real risk. […] DiGeorge Syndrome is considered one of the most common genetic syndromes, second only to Downs Syndrome. In the general population, its estimated to affect between 1 in 2,000 to 1 in 4,000 live births. Younger women have the same chance to deliver baby with 22q del as older ones.

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