Chromosome 22q11 Deletion Syndrome:( Also known as DiGeorge or Velo-Cardio-Facial Syndrome).

The aim of this study was to determine whether deletion 22q11.2 studies should become apart of a standardized diagnostic workup for selected groups of at risk patients. We prospectively investigated four cohorts of unselected patients referred because of 1) congenital heart defect (CHD), 2) palatal anomalies, 3) hypocalcaemia, 4) dysmorphic features suggestive of del 22q11.2. Fluorescence in situ hybridization analysis revealed deletion 22q11.2 in 9.4% (6/64) patients with CHD. From 18 patients referred because of the hypocalcaemia, six (33.3%) had 22q11.2 deletion. In the group of 31 children with dysmorphic traits, the diagnosis was confirmed in two (6.4%) patients. None of the 58 children with palatal anomalies showed evidence of 22q11.2 deletion. Conclusions: Testing for the 22q11.2 microdeletion can be recommended in all patients with conotruncal heart defects and in patients with hypocalcaemia. It should be also considered in patients presenting only with dysmorphic traits suggestive of del 22q11.2, while screening in patients with cleft palate is not warranted.

The aim of this study was to investigate and describe the presenting phenotype of children with the 22q11 deletion syndrome and to describe common clinical features that could serve as guidelines in the clinical diagnostic process preceding genetic testing. A hospital-based study of 100 consecutive children and adolescents with 22q11 deletion was initiated. The patients were divided into two groups according to age at diagnosis: before or after 2 years of age. Clinical features were grouped into a core set of eight features: cardiac defects, non-visible/hypoplastic thymus or infection problems, hypocalcaemia, feeding difficulties, cleft palate/speech-language impairment, developmental delay/learning difficulties, characteristic dysmorphic features and other malformations and deformities. The median age at diagnosis was 6.7 years. Of all patients, 26% were diagnosed in infancy and 92% had a congenital cardiac defect, whereas 54% of those diagnosed later had a cardiac defect. A cleft palate was present in 25 cases and 44 had some other malformation or deformity. All presented with a combination of many of the core features. Of those diagnosed after 2 years of age, the majority presented with speech-language impairment, developmental delay or learning difficulties and recurrent infections. Characteristic mild dysmorphic features were noticed in all children. Conclusion: In spite of variable clinical expression, children with 22q11 deletion share a number of major features and have a characteristic phenotype. A high proportion have no cardiac defect and hence a risk of diagnostic delay. Increased awareness and knowledge among general paediatricians and other specialists who meet these children early in life is needed to reduce the diagnostic delay.

BACKGROUND AND OBJECTIVE: Congenital cardiovascular (c-v) malformations are the leading signs of two syndromes of highly variable phenotypes, the DiGeorge syndrome (DGS) and the velo-cardio-facial syndrome (VCFS), both of which in the majority of cases are caused by microdeletion in the chromosome region 22q11.2. It was the aim of this study to ascertain the frequency of these chromosomal abnormalities in patients with unselected congenital cardiovascular malformation, and to assess the type of c-v malformation for which microdeletion analysis of the mentioned region would be indicated. PATIENTS AND METHODS: The cohort consisted of 90 patients with congenital c-v malformations (35 males, 55 females; mean age 3.6 years (19th week of pregnancy-36 years). Most of them were newborns. The c-v anomalies were: ventricular septal defect (n = 20), pulmonary atresia (10), Fallot's tetralogy (9), truncus arteriosus communis (6), aortic valve stenosis (6), atrioventricular canal (6), type B interrupted aortic arch (5), atrial septal defect (5), tricuspid atresia (4), hypoplastic left heart syndrome (4), persisting ductus arteriosus (3), pulmonary valve stenosis (3), complete (third degree) atrioventricular block (2), Ebstein's anomaly (1), tachycardia (1) and enlarged right atrium (1). Four of 14 fetuses included in this study had complex cardiac anomalies that could not be definitively classified. Cytogenetic karyotype analysis was unremarkable in all cases. Microdeletion detection was done by fluorescence-in-situ-hybridization (FISH). RESULTS: 14 of the 90 cases (about 16%) showed microdeletion in the examined chromosomal region 22q11.2. Among the group with microdeletion were aortic arch interruption (5/5), ventricular septal defect (2/20). Fallot's tetralogy (1/9) and atrial septal defect (1/5). All the deletion carriers had other signs of the DGS/VCFS complex. One parent each in two of the microdeletion patients had the same microdeletions. CONCLUSION: In patients with congenital c-v and associated malformations of dysmorphism microdeletion diagnosis of 22q11.2 by FISH is indicated in addition to conventional cytogenetic testing. The incidence of this microdeletion seems to be especially high among patients with type B interrupted aortic arch.

The 22q11 Deletion Syndrome (22q11DS, also known as DiGeorge or Velo-Cardio-Facial Syndrome) has a variable constellation of phenotypes including life-threatening cardiac malformations, craniofacial, limb, and digit anomalies, a high incidence of learning, language, and behavioral disorders, and increased vulnerability for psychiatric diseases, including schizophrenia. There is still little clear understanding of how heterozygous microdeletion of approximately 30-50 genes on chromosome 22 leads to this diverse spectrum of phenotypes, especially in the brain. Three possibilities exist: 1) 22q11DS may reflect haploinsufficiency, homozygous loss of function, or heterozygous gain of function of a single gene within the deleted region; 2) 22q11DS may result from haploinsufficiency, homozygous loss of function, or heterozygous gain of function of a few genes in the deleted region acting at distinct phenotypically compromised sites; 3) 22q11DS may reflect combinatorial effects of reduced dosage of multiple genes acting in concert at all phenotypically compromised sites. Here, we consider evidence for each of these possibilities. Our review of the literature, as well as interpretation of work from our laboratory, favors the third possibility: 22q11DS reflects diminished expression of multiple 22q11 genes acting on common cellular processes during brain as well as heart, face, and limb development, and subsequently in the adolescent and adult brain.

Primary amenorrhea and absent uterus in the 22q11.2 deletion syndrome.Am J Med Genet A. 2007 Sep 1;143A(17):2016-8.

The classic clinical features in the 22q11.2 deletion syndrome are congenital heart defects, hypocalcemia, immunodeficiency, learning, speech, and behavioral difficulties. The phenotype is highly variable and continues to expand. We present two cases of absent uterus and unilateral renal agenesis in females with the 22q11.2 deletion. Clinicians caring for these adolescents should be aware of the possibility of renal anomalies and Mullerian agenesis. The diagnosis of 22q11.2 deletion may be considered in a female with Mullerian agenesis, particularly, in association with a history of learning difficulties and speech delay.

A case of necrotizing enterocolitis associated with adenovirus infection in a term infant with 22q11 deletion syndrome.J Pediatr Surg. 2008 Apr;43(4):e5-8.

Infections with adenoviruses are a common problem in the pediatric population. Normally asymptomatic to mild, those infections tend to take a more severe course in immunocompromised patients. 22q11 deletion syndrome (22q11DS) represents a common genetic disorder causing immunodeficiency from thymic hypoplasia or aplasia, heart defects, a characteristic facial appearance, and velopharyngeal dysfunction. Necrotizing enterocolitis (NEC) is a frequent gastrointestinal emergency observed in neonatal intensive care units. The occurrence of NEC is more prevalent in preterm infants. However, there are cases in term infants, but usually, they are associated with predisposing disorders. In this case report, a child is presented with 22q11DS that postnatally developed NEC associated with an adenoviral infection. Although other viruses such as toroviruses or cytomegaloviruses have been implicated in the pathogenesis of NEC in preterm infants, we could not find any report in the recent medical literature describing an association between adenoviral infections, NEC, and 22q11DS in a term infant.