Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study.

Abstract

We present clinical data on 558 patients with deletions within the DiGeorge syndrome critical region of chromosome 22qll. Twenty-eight percent of the cases where parents had been tested had inherited deletions, with a marked excess of maternally inherited deletions (maternal 61, paternal 18). Eight percent of the patients had died, over half of these within a month ofbirth and the majority within 6 months. All but one of the deaths were the result of congenital heart disease. Clinically significant immunological problems were very uncommon. Nine percent of patients had cleft palate and 32% had velopharyngeal insufficiency, 60% of patients were hypocalcaemic, 75% of patients had cardiac problems, and 36% of patients who had abdominal ultrasound had a renal abnormality. Sixty-two percent of surviving patients were developmentally normal or had only mild learning problems. The majority of patients were constitutionally small, with 36% of patients below the 3rd centile for either height or weight parameters. (JMed Genet 1997;34:798-804) Data collectionParticipating centres from Europe were sent data questionnaires relating to cases of proven deletions within chromosome band 22ql 1. The probes and microsatellite markers used varied between centres but all mapped within the DGS region.2 Centres were asked to send information on all their cases, whether previously published or not. The data for all UK centres was collected by one person (AR) who also entered information into the database from the returned questionnaires. Data were requested on heart, palate, renal, and thymus abnormalities, parathyroid function, growth, developmental status, behaviour, and psychiatric illness. All available patient information was entered into an anonymous central database. Some questionnaires did not provide information on all sections, for example, the heart section was completed in more questionnaires than the renal section. Hence, the total number of patients for which data were recorded is specified in each section of the results.

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.…”

“…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. 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%.…”

Relationship between reaction time, fine motor control, and visual–spatial perception on vigilance and visual-motor tasks in 22q11.2 Deletion Syndrome

“…The condition is associated with a range of physical health problems, including congenital heart defects (e.g. Ryan et al, 1997), craniofacial dysmorphology (e.g. Shprintzen, Goldberg, Young, & Wolford, 1981) and velopharyngeal insufficiency, particular palatal anomalies (e.g.…”

Tbx1 regulation of myogenic differentiation in the limb and cranial mesoderm

“…Deletion of TBX1 has been linked to the majority of the abnormalities that occur in DiGeorge syndrome (DGS), which encompasses the facial region, derivatives of the branchial arches such as the thymus and parathyroid glands, and vascular/cardiac defects. DiGeorge syndrome affects approximately 1 in 4,000 births and is due to a 22q11.2 deletion, the most frequent chromosomal deletion in humans (Wilson et al, 1993;McDonaldMcGinn et al, 1997;Ryan et al, 1997;Botto et al, 2003). Whereas recent studies have implicated both Tbx1 and the adaptor protein CRK-L in the pathogenesis of this syndrome, point mutations in TBX1 in humans result in similar abnormalities, which is strongly suggestive that haploinsufficiency of TBX1 plays a major role (Yagi et al, 2003;Guris et al, 2006;Paylor et al, 2006).…”