DiGeorge syndrome
You don't need to be Editor-In-Chief to add or edit content to WikiDoc. You can begin to add to or edit text on this WikiDoc page by clicking on the edit button at the top of this page. Next enter or edit the information that you would like to appear here. Once you are done editing, scroll down and click the Save page button at the bottom of the page.
| DiGeorge syndrome Classification and external resources | |
| ICD-10 | D82.1 |
|---|---|
| ICD-9 | 279.11, 758.32 |
| OMIM | 188400 |
| DiseasesDB | 3631 |
| eMedicine | med/567 ped/589 derm/716 |
| MeSH | D004062 |
|
WikiDoc Resources for DiGeorge syndrome | |
|
Articles | |
|---|---|
|
Most recent articles on DiGeorge syndrome Most cited articles on DiGeorge syndrome | |
|
Media | |
|
Powerpoint slides on DiGeorge syndrome | |
|
Evidence Based Medicine | |
|
Cochrane Collaboration on DiGeorge syndrome | |
|
Clinical Trials | |
|
Ongoing Trials on DiGeorge syndrome at Clinical Trials.gov Trial results on DiGeorge syndrome Clinical Trials on DiGeorge syndrome at Google
| |
|
Guidelines / Policies / Govt | |
|
US National Guidelines Clearinghouse on DiGeorge syndrome NICE Guidance on DiGeorge syndrome
| |
|
Books | |
|
News | |
|
Commentary | |
|
Definitions | |
|
Patient Resources / Community | |
|
Patient resources on DiGeorge syndrome Discussion groups on DiGeorge syndrome Patient Handouts on DiGeorge syndrome Directions to Hospitals Treating DiGeorge syndrome Risk calculators and risk factors for DiGeorge syndrome
| |
|
Healthcare Provider Resources | |
|
Causes & Risk Factors for DiGeorge syndrome | |
|
Continuing Medical Education (CME) | |
|
International | |
|
| |
|
Businness | |
|
Experimental / Informatics | |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-525-6884
Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [2] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
22q11.2 deletion syndrome, Di George Syndrome, Strong Syndrome is a disorder caused by the deletion of a small piece of chromosome 22. The deletion occurs near the middle of the chromosome at a location designated q11.2. It has a birth incidence estimated at 1:4000.[1]
Presentation
The features of this syndrome vary widely, even among members of the same family, and affect many parts of the body. Characteristic signs and symptoms include heart defects that are often present from birth, an opening in the roof of the mouth (a cleft palate or other defect in the palate), autism, other learning disabilities, recurrent infections caused by problems with the immune system, and mild differences in facial features. Affected individuals may also have kidney abnormalities, low levels of calcium in the blood (which can result in seizures), significant feeding difficulties, autoimmune disorders such as rheumatoid arthritis, and an increased risk of developing mental illnesses.[1] Microdeletions in chromosomal region 22q11 are associated with a roughly 30-fold increased risk of schizophrenia, [1] and are frequently detected in schizophrenic patients. Different studies provide different occurrence rates, ranging from 0.5 to 3%, compared with the overall 0.025% risk of the 22q11 deletion syndrome in the general population.[1]
Nomenclature
Because the signs and symptoms of 22q11.2 deletion syndrome are so varied, different groupings of features were once described as separate conditions. These included the velo-cardio-facial syndrome (also called Shprintzen's syndrome), DiGeorge syndrome, hearing loss with craniofacial syndromes and conotruncal anomaly face syndrome, thymic hypoplasia, cleft palate, psychiatric disorders, and hypocalcaemia. The acronym CATCH-22 (C = cardiac defects, A = abnormal facies, T = thymic hypoplasia, C = cleft palate, H = hypocalcemia from parathyroid aplasia, 22 = microdeletions in chromosome 22) is sometimes used, although it is widely rejected because of the negative connotations with catch 22 meaning a 'no-win' situation.
In addition, some children with the 22q11.2 deletion were diagnosed with Opitz G/BBB syndrome and Cayler cardiofacial syndrome. Once the genetic basis for these disorders was identified, doctors determined that they were all part of a single syndrome with many possible signs and symptoms. To avoid confusion, this condition is usually called 22q11.2 deletion syndrome, a description based on its underlying genetic cause.
Symptoms
Individuals with a 22q11 deletion can suffer from a range of over 200 possible symptoms, ranging from the mild to the very serious. Possible symptoms are:
- Congenital heart disease (74% of individuals), particularly conotruncal malformations (tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, and persistent truncus arteriosus)
- palatal abnormalities (69%), particularly velopharyngeal incompetence (VPI), submucosal cleft palate, and cleft palate; characteristic facial features (present in the majority of Caucasian individuals) including hypertelorism.
- learning difficulties (70-90%)
- an immune deficiency regardless of their clinical presentation (77%)
- hypocalcemia (50%)
- significant feeding problems (30%)
- renal anomalies (37%)
- hearing loss (both conductive and sensorineural) (Hearing loss with craniofacial syndromes)
- laryngotracheoesophageal anomalies
- growth hormone deficiency
- autoimmune disorders
- seizures (without hypocalcemia)
- skeletal abnormalities
- Autism and Autism spectrum disorders
Thymus, parathyroid glands and heart derive from the same primitive embryonic structure and that is why these three organs are dysfunctioned together in this disease. Affected patients (usually children) are prone to yeast infections.
Cause
The syndrome is caused by genetic deletions (loss of a small part of the genetic material) found on the long arm of the 22nd chromosome. Some patients with similar clinical features may have deletions on the short arm of chromosome 10.
DiGeorge syndrome causes migration defects of neural crest-derived tissues, particularly affecting development of the third and fourth Branchial pouches (pharyngeal pouches). Also affected is the thymus gland; a mediastinal organ largely responsible for differentiation and induction of tolerance in T-cells. Impaired immune function results principally from this aetiology.
Treatment
Although genetic transplantation methods are currently being developed by researchers, there is yet no genetic treatment of this disease.
Treatment is largely symptomatic, that is calcium is administered, infections are treated with antibiotics, and these patients may undergo cardiac surgery for their heart abnormalities.
Thymus transplantation is used to address absence of the thymus in complete DiGeorge syndrome.[1]
Diagnosis/testing
The 22q11.2 deletion syndrome is diagnosed in individuals with a submicroscopic deletion of chromosome 22 detected by fluorescence in situ hybridization (FISH) using DNA probes from the DiGeorge chromosomal region (DGCR). Such genetic testing is widely available for the clinical and prenatal testing of the 22q11.2 deletion syndrome. Fewer than 5% of individuals with clinical symptoms of the 22q11.2 deletion syndrome have normal routine cytogenetic studies and negative FISH testing. They may have variant deletions of DiGeorge syndrome that may be detectable on a research basis only.
Genetics
Most people with 22q11.2 deletion syndrome are missing about 3 million base pairs (the building blocks of DNA) on one copy of chromosome 22 in each cell. This region contains about 30 genes, but many of these genes have not been well characterized. A small percentage of affected individuals have shorter deletions in the same region. This condition is often described as a contiguous gene deletion syndrome because a deletion in chromosome 22 leads to the loss of many genes.
Researchers have not yet identified all of the genes that contribute to the features of 22q11.2 deletion syndrome. They have determined that the loss of one 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, and low calcium levels). A loss of this gene does not appear to cause learning disabilities, however. Additional genes in the deleted region are likely to contribute to the signs and symptoms of 22q11.2 deletion syndrome.
The 22q11.2 deletion syndrome can be inherited in an autosomal dominant manner. Almost all (about 93%) of cases have a de novo (new to the family) deletion of 22q11.2 but about 7% inherit the 22q11.2 deletion from a parent. Children of an individual with deletion 22q11.2 have a 50% chance of inheriting the 22q11.2 deletion. Prenatal testing, such as amniocentesis, is available for pregnancies determined to be at risk. Also pregnancies who have findings of congenital heart disease and/or cleft palate detected by ultrasound examination may be offered prenatal testing. Genetic counseling may be helpful for families who may have DiGeorge syndrome. Because most of the signs of this cluster of defects can also be inherited as autosomal recessive or x-linked traits, only genetic testing of both parents can determine with any certainty the likelihood these anomalies occurring in any subsequent children.
Epidemiology
22q11.2 deletion syndrome affects an estimated 1 in 4000 live births. The condition may be more common, however, because some people with the deletion have few signs and symptoms and may not have been diagnosed.
Speech and Language
Current research demonstrates there is a unique profile of speech and language impairments associated with 22q11.2 deletion syndrome. Children often perform lower on speech and language evaluations in comparison to their nonverbal IQ scores. Common problems include hypernasality, language delays, and speech sound errors.[1][1][1]
Hypernasality occurs when air escapes through the nose during the production of oral speech sounds resulting in reduced intelligibility. This is a common characteristic in the speech and language profile because 69% of children have palatal abnormalities. If the structure of the soft palate velum is such that it does not stop the flow of air from going up to the nasal cavity, it will cause hypernasal speech. This phenomenon is referred as velopharyngeal inadequacy VPI. Hearing loss can also contribute to increased hypernasality because children with hearing impairments can have difficulty self monitoring their oral speech output. The treatment options available for VPI include prosthesis and surgery. [1] [1][1][1][1]
Difficulties acquiring vocabulary and formulating spoken language (expressive language deficits) at the onset of language development are also part of the speech and language profile associated with the 22q11.2 deletion. Vocabulary acquisition is often severely delayed for preschool age children. In some recent studies, children had a severely limited vocabulary or were still nonverbal at 2-3 years of age. School age children do make progress with expressive language as they mature, but many continue to have delays and demonstrate difficulty when presented with language tasks such as verbally recalling narratives and producing longer and more complex sentences. Receptive language, which is the ability to comprehend, retain, or process spoken language, can also be impaired although not usually with the same severity as expressive language impairments. [1][1][1][1]
Articulation errors are commonly present in children with 22q11.2 deletion syndrome. These errors include a limited phonemic (speech sound) inventory and the use of compensatory articulation strategies resulting in reduced intelligibility. The phonemic inventory typically produced consists of sounds made in the front or back of the vocal tract such as: /p/, /w/, /j/, /m/, /n/, and glottal stops. Mid vocal tract sounds are completely absent. Compensatory articulation errors made by this population of children include: glottal stops, nasal substitutions, pharyngeal fricatives, linguapalatal sibilants, reduced pressure on consonant sounds, or a combination of these symptoms. Of these errors, glottal stops have the highest frequency of occurrence. It is reasoned that a limited phonemic inventory and the use of compensatory articulation strategies is present due to the structural abnormalities of the palate. The speech impairments exhibited by this population are more severe during the younger ages and show a trend of gradual improvement as the child matures. [1][1]
See also
References
This article incorporates public domain text from The U.S. National Library of Medicine
External links
- GeneReviews: 22q11.2 deletion syndrome
- India Knight's blog about children with special needs. Her daughter suffers from 22q11.2 Deletion Syndrome
- VCFS Educational Foundation, Inc.
- Children's Hospital of Philadelphia
- NIH
- MaxAppeal
- International 22q11.2 Deletion Syndrome Foundation
- Asoc. Familias 22q11 DS/VCFS
Acknowledgements
The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.
fr:Microdélétion 22q11
id:Sindrom delesi 22q11
it:Sindrome da delezione 22q11
nl:Syndroom van DiGeorge
sv:22q11-deletionsyndromet
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
