22q11.2 deletion syndrome

Abstract

22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, estimated to result mainly from de novo non-homologous meiotic recombination events occurring in approximately 1 in every 1,000 fetuses. The first description in the English language of the constellation of findings now known to be due to this chromosomal difference was made in the 1960s in children with DiGeorge syndrome, who presented with the clinical triad of immunodeficiency, hypoparathyroidism and congenital heart disease. The syndrome is now known to have a heterogeneous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as palatal, gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioural phenotypes and psychiatric illness — all far extending the original description of DiGeorge syndrome. Management requires a multidisciplinary approach involving paediatrics, general medicine, surgery, psychiatry, psychology, interventional therapies (physical, occupational, speech, language and behavioural) and genetic counselling. Although common, lack of recognition of the condition and/or lack of familiarity with genetic testing methods, together with the wide variability of clinical presentation, delays diagnosis. Early diagnosis, preferably prenatally or neonatally, could improve outcomes, thus stressing the importance of universal screening. Equally important, 22q11.2DS has become a model for understanding rare and frequent congenital anomalies, medical conditions, psychiatric and developmental disorders, and may provide a platform to better understand these disorders while affording opportunities for translational strategies across the lifespan for both patients with 22q11.2DS and those with these associated features in the general population.

A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

“…4,5 According to the literature, the 22q11.2 deletion occurs de novo in 90% of cases and therefore is inherited in the remaining 10%. 3,[5][6][7][8] In our prenatal series of 272 fetuses with 22q11.2DS, 27% of the deletions were inherited. 9 Of the inherited deletions, 72 to 77% are of maternal origin.…”

“…Even though the CHD was generally a conotruncal disorder (including tetralogy of Fallot, interrupted aortic arch, etc), the most common CHD in our postnatally diagnosed patients was an isolated septal defect. The literature data on cases of 22q11.2DS (most of which are diagnosed postnatally) suggest that the frequency of a CHD is between 31.1 and 80.0%, 1,3,5,7,8,32,33 with tetralogy of Fallot and a ventricular septal defect being the most frequent. 3,7,8,33,34 Of the 15 patients diagnosed using aCGH, 3 had a CHD (including 2 with a deletion encompassing the TBX1 gene that is strongly suspected to be involved in CHDs 18 ) and the third patient (patient 15) had a distal deletion encompassing CRKL (also suspected to be involved in Postnatal diagnosis of 22q11 deletions C Poirsier et al CHDs 23 ) (Figure 3).…”

“…1,2 The phenotype is highly variableover 180 associated clinical manifestations already described -and ranges from severe, with life-threatening malformations, to nearly asymptomatic cases. The major clinical features include congenital heart defects (CHDs), palate defects (velopharyngeal insufficiency, cleft palate, etc), mild-to-moderate immunodeficiency (because of thymic aplasia or hypoplasia), hypocalcemia caused by hypoparathyroidism, a distinct gestalt, developmental delay (DD), learning 1 Département de Génétique, CHU de Reims, Reims, France; 2 Service de Cytogénétique, Hôpital Poissy/Saint-Germain-en-Laye, Poissy, France; 3 Service de Cytogénétique, CHU de Lyon, Lyon, France; 4 CHU Bordeaux, Génétique Médicale, Bordeaux, France; 5 Laboratoire de Cytogénétique, CHU de Marseille, Marseille, France; 6 CHU Nantes, Service de Génétique Médicale, Inserm UMR957, Faculté de Médecine, Nantes, France; 7 Laboratoire de Cytogénétique Pasteur-Cerba, Saint-Ouen l'Aumône, France; 8 Service de Cytogénétique, CHU de Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; 9 Service de Cytogénétique, CHU de Besançon, Besançon, France; 10 Service de Cytogénétique, Biolille, Lille, France; 11 Service de Cytogénétique, Hôpital Saint Vincent de Paul, Paris, France; 12 Laboratoire de Cytogénétique Postnatal, CHU Clemenceau, Caen, France; 13 Service de Cytogénétique et Biologie de la Reproduction, CHRU de Brest, Brest, France; 14 Service de Cytogénétique, CHU de Robert Debré, Paris, France; 15 Service de Cytogénétique, CHU de Strasbourg, Strasbourg, France; 16 Service de Cytogénétique, CHU de Tours, Tours, France; 17 Service de Cytogénétique, CHU de Nancy, Nancy, France; 18 Laboratoire de Cytogénétique Cylab, La Rochelle, France; 19 Service de Cytogénétique, Hôpital de Saint-Denis, Saint-Denis de la Réunion, France; disabilities, intellectual disability (ID) and behavioral disturbances. [3][4][5] Renal, ocular and skeletal anomalies have also been observed.…”

The 22Q11.2 Deletion Syndrome

“…2 deletion these overlapping features of 22q11. 2 deletion syndrome are seen in; Smith -Lemli-Optiz syndrome when there is polydactyly and cleft palate are present in this group molecular genetics formutation of the DHCR7 gene is available for this diagnosis, other one is Alagille syndrome when there is congenital heart disease and butterfly vertebra is present and also in Goldenhar syndrome when there is vertebral, renal anomalies and congenital heart disease are present [11] .…”

“…Genitourinary anomalies are usually asymptomatic, renal anomalies including large (Figure 13) or small kidney single kidney, renal agenesis, echogenic kidney, multicystic dysplastic kidney, horseshoe kidney duplicated collecting system and vesicoureteral reflux, absent uterus are seen in this children [11,12,13] .…”