conotruncal anomaly face syndrome

WordNet

1. turn so as to face; turn the face in a certain direction; "Turn and face your partner now"
2. a vertical surface of a building or cliff
3. the general outward appearance of something; "the face of the city is changing"
4. the side upon which the use of a thing depends (usually the most prominent surface of an object); "he dealt the cards face down"
5. the striking or working surface of an implement
6. the front of the human head from the forehead to the chin and ear to ear; "he washed his face"; "I wish I had seen the look on his face when he got the news" (同)human face
7. a part of a person that is used to refer to a person; "he looked out at a roomful of faces"; "when he returned to work he met many new faces"
8. status in the eyes of others; "he lost face"
9. the part of an animal corresponding to the human face
10. be opposite; "the facing page"; "the two sofas face each other"
11. cover the front or surface of; "The building was faced with beautiful stones"
12. line the edge (of a garment) with a different material; "face the lapels of the jacket"
13. turn so as to expose the face; "face a playing card"
14. deviation from the normal or common order or form or rule (同)anomalousness
15. a person who is unusual (同)unusual person
16. (astronomy) position of a planet as defined by its angular distance from its perihelion (as observed from the sun)
17. a protective covering that protects the outside of a building (同)cladding
18. an ornamental coating to a building (同)veneer
19. a lining applied to the edge of a garment for ornamentation or strengthening
20. a pattern of symptoms indicative of some disease
21. a complex of concurrent things; "every word has a syndrome of meanings"
22. having a face or facing especially of a specified kind or number; often used in combination; "a neatly faced terrace"

PrepTutorEJDIC

1. 〈C〉『顔』 / 〈C〉表情,顔つき / 〈C〉(物の)『表面』(surface),(建物の)正面(front),(貨幣・カードなどの)表《+『of』+『名』》 / 〈C〉(…の)外観,様子《+『of』+『名』》 / 〈U〉面目,面子(めんつ) / 〈C〉(多角面体の)面 / 〈C〉(活字・版の)面(印刷する部分);(活字の)書体 / 〈C〉(鉱山の)採掘現場 / …‘に'『面する』,‘の'ほうを向く / (…のほうに)…‘を'向ける《+『名』+『toward』+『名』》 / 〈人が〉〈危険など〉‘に'直面する,立ち向かう,対抗する;〈危険などが〉〈人〉‘に'迫る / 〈事実・現実など〉‘を'直視する,認める / (…で)〈壁など〉‘に'上塗り(上張り)をする《+『名』+『with』+『名』》 / (ある場所・方角に)面する,向く《+『on』(『to』,『toward』)+『名』》
2. 〈U〉〈C〉変則,例外;異常 / 〈C〉変則的な事態,異例な人(物)
3. 〈U〉(壁などの)表面仕上げ,化粧張り / 〈U〉(着年の)へり取り,へり飾り / 《複数形で》(軍服のえりやそで口につけ,兵種・職種を示す)縫い取り,定色
4. (疾患の徴候となる一群の)症徴候,症候群 / (事件・社会的状態などのパターンを示す)徴候形態
5. (…に)面した,直面した《+『with』+『名』》 / 上張りをした,縁飾りをした

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/02/04 22:31:35」(JST)

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22q11.2 deletion syndrome
Brain computer tomography cuts of the patient, demonstrating basal ganglia and periventricular calcification. From a case report by Tonelli et al., 2007
Classification and external resources
Specialty	Medical genetics
ICD-10	D82.1
ICD-9-CM	279.11, 758.32
OMIM	188400
DiseasesDB	3631
eMedicine	med/567 ped/589derm/716
Patient UK	DiGeorge syndrome
MeSH	D004062
GeneReviews	22q11.2 Deletion Syndrome
Orphanet	567

DiGeorge syndrome is also known as 22q11.2 deletion syndrome,DiGeorge anomaly, velocardiofacial syndrome (VCFS), Shprintzen syndrome, conotruncal anomaly face syndrome (CTAF) or Takao syndrome, Sedlackova syndrome, Cayler cardiofacial syndrome, Strong syndrome, congenital thymic aplasia, and thymic hypoplasia. This syndrome is caused by the deletion of a small piece of chromosome 22. As such, it is recommended that the name "22q11.2 deletion syndrome (22q11.2DS)" be used.

22q11.2DS is the most common microdeletion syndrome characterized by low copy repeats and the deletion occurs near the middle of the chromosome at a location designated 22q11.2—signifying its location on the long arm of one of the pair of chromosomes 22, on region 1, band 1, sub-band 2. The inheritance pattern is autosomal dominant and it has a prevalence estimated at 1:4000. The syndrome was described in 1968 by the pediatric endocrinologist Angelo DiGeorge. 22q11 deletion is also associated with truncus arteriosus and tetralogy of Fallot.

Signs and symptoms

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 may include birth defects such as congenital heart disease, defects in the palate, most commonly related to neuromuscular problems with closure (velopharyngeal insufficiency), learning disabilities, mild differences in facial features, and recurrent infections. Infections are common in children due to problems with the immune system's T-cell-mediated response that in some patients is due to an absent or hypoplastic thymus. 22q11.2 deletion syndrome may be first spotted when an affected newborn has heart defects or convulsions from hypocalcemia due to malfunctioning parathyroid glands and low levels of parathyroid hormone (parathormone). Affected individuals may also have other kinds of birth defect including kidney abnormalities and significant feeding difficulties as babies. Gastrointestinal issues are also very common in this patient population. Digestive motility issues may result in constipation. Disorders such as hypothyroidism and hypoparathyroidism or thrombocytopenia (low platelet levels), and psychiatric illnesses are common late-occurring features.

Microdeletions in chromosomal region 22q11.2 are associated with a 20 to 30-fold increased risk of schizophrenia. Studies provide various rates of 22q11.2 deletion syndrome in schizophrenia, ranging from 0.5 to 2.0% and averaging about 1.0%, compared with the overall estimated 0.025% risk of the 22q11.2 deletion syndrome in the general population.

Salient features can be summarized using the mnemonic CATCH-22 to describe DiGeorge syndrome, with the 22 to remind one the chromosomal abnormality is found on the 22 chromosome, as below:

Cardiac abnormality (especially tetralogy of Fallot)
Abnormal facies
Thymic aplasia
Cleft palate
Hypocalcemia/Hypoparathyroidism

Individuals with a 22q11.2 deletion can have many possible features, ranging in number of associated features and from the mild to the very serious. Symptoms shown to be common include:

• Congenital heart disease (40% of individuals), particularly conotruncal malformations (tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, and persistent truncus arteriosus)
• Cyanosis (bluish skin due to poor circulation of oxygen-rich blood)
• Palatal abnormalities (50%), particularly velopharyngeal incompetence, submucosal cleft palate, and cleft palate; characteristic facial features (present in the majority of Caucasian individuals) including hypertelorism
• Learning difficulties (90%), including cognitive deficits, attention deficit disorders
• Hypocalcemia (50%)(due to hypoparathyroidism)
• 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
• Immune disorders due to reduced T cell numbers
• Seizures (with or without hypocalcemia)
• Skeletal abnormalities
• Psychiatric disorders

This syndrome is characterized by incomplete penetrance and therefore there is a marked variability in clinical expression between the different patients. This often makes early diagnosis difficult.

Cognitive impairments

Children with 22q11.2 have a specific profile in neuropsychological tests. They usually have a below-borderline normal IQ, with most individuals having higher scores in the verbal than the nonverbal domains. Some are able to attend normal schools, while others are home-schooled or in special classes.The severity of hypocalcemia early in childhood is associated with autism-like behavioral difficulties.

Adults with DiGeorge syndrome have a specifically high-risk group for developing schizophrenia. About 30% have at least one incident of psychosis and about a quarter develop actual schizophrenia.

Individuals with 22q11.2DS also have a higher risk of developing early onset Parkinson's disease (PD). Diagnosis of PD in 22q11.2DS patients can be delayed by up to 10 years due to the use of antipsychotics, which can cause parkinsonian symptoms.

Speech and language

Current research demonstrates a unique profile of speech and language impairments is 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.

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.

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 not verbal 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.

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 oral cavity such as: /p/, /w/, /m/, /n/, and glottal stops. Sound made in the middle of the mouth 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.

Genetics

22q11.2 deletion syndrome is inherited in an autosomal dominant pattern.

DiGeorge Syndrome is caused by a hemizygous 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 3Mb and 8% have a deletion of 1.5Mb. The number of genes affected by the deletion has been cited as approximately 30 to 50. Very rarely, patients with somewhat similar clinical features may have deletions on the short arm of chromosome 10. The disorder has an autosomal dominant inheritance pattern. A French study of 749 people diagnosed between 1995 and 2013 found that the mutation was inherited in 15% of patients, of which 85.5% was from the mother. Other studies have found inheritance rates of 6-10%. The majority cases are a result of a de novo (new to the family) deletion. This is because the 22q11 reagon has a structure that makes it highly prone to rearrangements during sperm or egg formation.

The exact mechanism that causes all of the associated features of the syndrome is unknown. Of the 30-50 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.

TBX1

Haploinsufficiency of the TBX1 gene (T-box transcription factor TBX1) is thought to be the cause of some of the symptoms observed. Point mutations in this gene have also been observed in individuals with DiGeorge syndrome. TBX1 is part of the T-box family of genes which have an important role in tissue and organ formation during embryonic development and it may have a role in the regulation of differentiation of post migration neural crest cells. The neural crest forms many of the structures affected in DiGeorge Syndrome, including the skull bones, mesenchyme of the face and palate, the outflow tract of the heart, and the thymus and parathyroid stroma. When there is a loss of expression of FGF18 during the development of the pharyngeal arches, neural crest cell death is seen. Although neither FGF18 or TBX1 are expressed in the neural crest cells, TBX1 might have a role in the regulation of FGF18 expression, ensuring that the differentiation of the these cells in the pharyngeal region is correct. Therefore, dysfunction of TBX1 may be responsible for some of the symptoms in DiGeorge Syndrome.

Parkinson's disease genes

22q11.2DS has been associated with a higher risk of early onset Parkinson's disease (PD). The neuropathology seen is similar to LRRK2-associated PD. None of the genes affected in individuals with 22q11.2DS have previously been linked to PD but there are a number that are likely candidates. These include DGCR8 which is important for biogenesis of brain mircoDNA, SRPT5 which encodes a protein that interacts with the PARK2 protein, COMT which is involved in regulating dopamine levels, and microRNA miR-185 which is thought to target known PD loci LRRK2.

Diagnosis

Result of FISH analysis using LSI probe (TUPLE 1) from DiGeorge/velocardiofacial syndrome critical region. TUPLE 1 (HIRA) probe was labeled in Spectrum Orange and Arylsulfatase A (ARSA) in Spectrum Green as control. Absence of the orange signal indicates deletion of the TUPLE 1 locus at 22q11.2.

Diagnosis of 22q11.2 deletion syndrome can be difficult due to the number of potential symptoms and the variation in phenotypes between individuals. It is suspected in patients with one or more signs of the deletion. In these cases a diagnosis of 22q11.2DS is confirmed by observation of a deletion of part of the long arm (q) of chromosome 22, region 1, band 1, sub-band 2. Genetic analysis is normally performed using fluorescence in situ hybridization (FISH), which is able to detect microdeletions that standard keryotyping (e.g. G-banding) miss. Newer methods of analysis include Multiplex ligation-dependent probe amplification assay (MLPA) and quantitative polymerase chain reaction (qPCR), both of which can detect atypical deletions in 22q11.2 that are not detected by FISH. qPCR analysis is also quicker than FISH, which can have a turn around of 3 to 14 days. A 2008 study of a new high-definition MLPA probe developed to detect copy number variation at 37 points on chromosome 22q found it to be as reliable as FISH in detecting normal 22q11.2 deletions. It was also able to detect smaller atypical deletions that are easily missed using FISH. These factors, along with the lower expense and easier testing mean that this MLPA probe could replace FISH in clinical testing.

Genetic testing using BACs-on-Beads has been successful in detecting deletions consistent with 22q11.2DS during prenatal testing. Array-comparative genomic hybridization (array-CGH) uses a large number of probes embossed in a chip to screen the entire genome for deletions or duplications. It can be used in post and pre-natal diagnosis of 22q11.2.

Fewer than 5% of individuals with clinical symptoms of the 22q11.2 deletion syndrome have normal routine cytogenetic studies and negative FISH testing. In these cases atypical deletions are the cause. Some cases of DiGeorge syndrome have defects in other chromosomes, notably a deletion in chromosome region 10p14.

Treatment

No cure is known for 22q11.2 deletion syndrome. Certain individual features are treatable using standard treatments. The key is to identify each of the associated features and manage each using the best available treatments.

For example, in children, it is important that the immune problems are identified early, as special precautions are required regarding blood transfusion and immunization with live vaccines. Thymus transplantation can be used to address absence of the thymus in the rare, so-called "complete" DiGeorge syndrome. Bacterial infections are treated with antibiotics. Cardiac surgery is often required for congenital heart abnormalities. Hypoparathyroidism causing hypocalcaemia often requires lifelong vitamin D and calcium supplements.

Epidemiology

22q11.2 deletion syndrome was estimated to affect between one in 2000 and one in 4000 live births. This estimate is based on major birth defects and may be an underestimate, because some individuals with the deletion have few symptoms and may not have been formally diagnosed. It is one of the most common causes of mental retardation due to a genetic deletion syndrome.

The prevalence of 22q11.2DS has been expected to rise because of multiple reasons: (1) Thanks to surgical and medical advances, an increasing number of people are surviving heart defects associated with the syndrome. These individuals are in turn having children. The chances of a 22q11.2DS patient having an affected child is 50% for each pregnancy; (2) Parents who have affected children, but who were unaware of their own genetic conditions, are now being diagnosed as genetic testing become available; (3) Molecular genetics techniques such as FISH (fluorescence in situ hybridization) have limitations and have not been able to detect all 22q11.2 deletions. Newer technologies have been able to detect these atypical deletions.

Recently, the syndrome has been estimated to affect up to one in 2000 live births. Testing for 22q11.2DS in over 9500 pregnancies revealed a prevalence rate of 1/992.

Nomenclature

The signs and symptoms of 22q11.2 deletion syndrome are so varied that different groupings of its features were once regarded as separate conditions. These original classifications included velocardiofacial syndrome, Shprintzen syndrome, DiGeorge sequence/syndrome, Sedlackova syndrome, and conotruncal anomaly face syndrome. All are now understood to be presentations of a single syndrome.

ICD-10 2015 version mentions 22q11.2DS using two codes: D82.1 (Di George syndrome) and Q93.81 (Velo-cardio-facial syndrome). The ICD-11 Beta Draft discusses the syndrome under “LD50.P1 CATCH 22 phenotype". However, since this syndrome is caused by the deletion of a small piece of chromosome 22, it is recommended that the name "22q11.2 deletion syndrome (22q11.2DS)" be used.

See also

• 22q11.2 duplication syndrome
• Asymmetric crying facies
• Contiguous gene syndrome
• DGCR2
• List of radiographic findings associated with cutaneous conditions
• Genetic counseling
• Zellweger syndrome
• CHARGE syndrome

References

This article incorporates public domain text from The U.S. National Library of Medicine

External links

Media related to DiGeorge Syndrome at Wikimedia Commons

• DiGeorge syndrome at DMOZ
• Velo-Cardio-Facial Syndrome Information Foundation
• McDonald-McGinn DM, Emanuel BS, Zackai EH (December 16, 2005). "22q11.2 Deletion Syndrome". In Pagon RA, Bird TD, Dolan CR, Stephens K. GeneReviews. PMID 20301696. NBK1523. 
• Firth HV (February 17, 2009). "22q11.2 Duplication". In Pagon RA, Bird TD, Dolan CR, Stephens K. GeneReviews. PMID 20301749. NBK3823. 
• Information on 22q11.2 Deletion syndrome from Seattle Children's Hospital

UpToDate Contents

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• 1. 頭蓋顔面異常を伴う症候群syndromes with craniofacial abnormalities [show details]
  …deletion has also been identified in the majority of patients with DiGeorge sequence and conotruncal anomaly face syndrome, suggesting that these are phenotypic variants of the same disorder . The deletion …
• 2. 先天異常：疫学、種類、パターンbirth defects epidemiology types and patterns [show details]
  … Examples of minor anomalies include ear tags, clinodactyly (incurving of the fifth finger) , and single transverse palmar creases Minor anomalies are common,… holoprosencephaly; Transcription factors – Conotruncal heart defects in DiGeorge syndrome caused by deletions of T-box 1 (TBX1) ,… affected because the embryonic forebrain in turn influences mesoderm developmental processes on the mid-face. Bladder exstrophy and cloacal exstrophy represent another developmental field defect. These conditions…
• 3. 口唇裂や口蓋裂の病因、出生前診断、産科マネージメント、再発etiology prenatal diagnosis obstetrical management and recurrence of cleft lip and or palate [show details]
  … associated with other unrelated structural anomalies (33.5 versus 28.2 percent with no other anomalies).… CL/P cannot be diagnosed reliably until the soft tissues of the fetal face can be clearly visualized sonographically,… associated with a spectrum of findings in addition to CP: conotruncal cardiac defects,…
• 4. 微細欠失症候群（1番～11番染色体）microdeletion syndromes chromosomes 1 to 11 [show details]
  … genitourinary anomalies (undescended testes, hypospadias), and gastrointestinal anomalies (pyloric stenosis, constipation). Limb anomalies include syndactyly of hands and feet,… intellectual disability, microcephaly (50 percent of cases), and mild dysmorphisms including a narrow face, large ears, short philtrum, and a high nasal bridge. Patients with this deletion may have autism … patients with 10p deletions that presented with conotruncal heart defects,…
• 5. エブスタイン奇形の臨床症状と診断clinical manifestations and diagnosis of ebstein anomaly [show details]
  …manifestations and diagnosis of Ebstein anomaly are discussed here. The management and prognosis of Ebstein anomaly are discussed separately. The estimated risk of Ebstein anomaly in the general population is …

English Journal

• Typical and Atypical Associated Findings in a Group of 346 Patients with Mayer-Rokitansky-Kuester-Hauser Syndrome.

• Rall K1, Eisenbeis S2, Henninger V2, Henes M2, Wallwiener D2, Bonin M3, Brucker S2.
• Journal of pediatric and adolescent gynecology.J Pediatr Adolesc Gynecol.2015 Oct;28(5):362-8. doi: 10.1016/j.jpag.2014.07.019. Epub 2014 Nov 11.
• STUDY OBJECTIVE: The Mayer-Rokitansky-Kuester-Hauser (MRKH) syndrome is characterized by vaginal and uterine aplasia in a 46,XX individual. Multiple abnormalities may be associated with MRKH syndrome, and it appears to overlap other syndromes. The aim of this study was to describe the spectrum of as
• PMID 26148785

• Routine Chromosomal Microarray Analysis is Necessary in Korean Patients With Unexplained Developmental Delay/Mental Retardation/Autism Spectrum Disorder.

• Shin S1, Yu N1, Choi JR1, Jeong S2, Lee KA3.
• Annals of laboratory medicine.Ann Lab Med.2015 Sep;35(5):510-8. doi: 10.3343/alm.2015.35.5.510.
• BACKGROUND: All over the world, chromosomal microarray (CMA) is now the first tier diagnostic assay for genetic testing to evaluate developmental delay (DD), mental retardation (MR), and autism spectrum disorder (ASD) with unknown etiology. The average diagnostic yield of the CMA test is known to be
• PMID 26206688

Japanese Journal

• 染色体22q11欠失症：発見と合併心疾患

• 日本小児循環器学会雑誌 33(1), 3-9, 2017
• NAID 130005530257

• 小児科領域における研究と治療の進歩(14)小児循環器疾患の研究と治療の進歩

• 東京女子医科大学雑誌 82(1), 1-6, 2012-02-25
• NAID 110008802807

• 22q11.2欠失症候群における喉頭病変

• 東京女子医科大学雑誌 77(9/10), 521-526, 2007-10
• NAID 110007525316

Related Links

• Conotruncal anomaly-face syndrome - RightDiagnosis.com

Conotruncal anomaly-face syndrome symptoms, causes, diagnosis, and treatment information for Conotruncal anomaly-face syndrome (Conotruncal heart malformations) with alternative diagnoses, full-text book chapters ...

• Conotruncal anomaly-face syndrome | definition of ...

DiGeorge Syndrome Definition DiGeorge syndrome (also called 22q11 deletion syndrome, congenital thymic hypoplasia, or third and fourth pharyngeal pouch syndrome) is a birth defect that is caused by an abnormality in ...

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リンク元	「円錐動脈幹異常顔貌症候群」
関連記事	「anomaly」「face」「syndrome」

「円錐動脈幹異常顔貌症候群」

　　[★]

英

conotruncal anomaly face syndrome

「anomaly」

　　[★]

• n.

• 異常、変則。異形。

関

aberrant、aberrantly、aberration、abnormal、abnormality、abnormally、anomalous、anomalously、defect、deviant、exceeding、exception、exceptional、extraordinarily、extraordinary、unusual、unusually

　 　 　 　

「face」

　　[★]

• n.

• 顔、顔貌

　 　 　 　 　 　 　 　 　 　 　 　 　 　

「syndrome」

　　[★]

• n.

• 症候群