Heart defects and other features of the 22q11 distal deletion syndrome

Fagerberg, Christina; Graakjær, Jesper; Heinl, Ulrike D.; Ousager, Lilian Bomme; Dreyer, Inken; Kirchhoff, Maria; Rasmussen, Anders Aamann; Lautrup, Charlotte Kvist; Birkebæk, Niels H; Sørensen, Keld E.

doi:10.1016/j.ejmg.2012.09.009

Cited by 32 publications

(50 citation statements)

References 50 publications

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“…8,9,12,15,17,18 A similar frequency of cardiac defects was noted in our study, with five patients (~42%) presenting with a history of a cardiac defect, including patent ductus arteriosus, atrial and ventricular septal defects, and bicuspid aortic…”

Section: Discussionsupporting

confidence: 85%

“…DD and/or ID have been reported in more than 80% of distal 22q11.2 microdeletion patients described in the literature to date and tend to be relatively mild to moderate in severity. [7][8][9][10][11][12][13][14][15][16][17][18] Taken together, global DD and ID seem to be key components of the distal 22q11.2 microdeletions phenotype irrespective of the size and position of the deletion. Behavioral and neurological problems were also quite common in our patients in all deletion types.…”

Section: Discussionmentioning

confidence: 93%

“…[7][8][9][10][11][12][13][14][15][16][17][18] These deletions are mediated by nonallelic homologous recombination between the five telomeric LCR22s (LCR22-D to -H) in the distal portion of the 22q11.2 region (Figure 2). 10 Distal 22q11.2 microdeletions that span the LCR22-F to -G interval encompassing the tumor suppressor SMARCB1 gene (also called INI1) have been reported to manifest many of the presenting features mentioned above but also have high incidence of malignant rhabdoid tumors in infancy and early childhood, predominantly in the kidneys and central nervous system, which necessitates tumor surveillance in these patients.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9][10][11][12][13][14][15][16][17][18] Moreover, some patients present with cleft lip and/or cleft palate. Although some of our patients manifested some of these features, the majority of them presented with nonspecific, nondiagnostic features that were quite variable, as shown in the Results section.…”

Section: Discussionmentioning

confidence: 99%

“…6 Recently, others and we demonstrated that the five telomeric LCR22s, namely LCR22-D to H, at the distal portion of 22q11.2 are causally implicated in the recurrent distal 22q11.2 microdeletion-associated phenotype(s) (OMIM 611867), and their reciprocal microduplications in the region immediately distal to the DG/VCFs typically deleted region (Figure 2). [7][8][9][10][11][12][13][14][15][16][17][18] The structure of the LCR22-D, -E, and -F has been studied and was shown to contain the BCRL module in each LCR22, suggesting that the distal 22q11.2 microdeletions/microduplications are mediated by nonallelic homologous recombination. 10 To date, the distal 22q11.2 microdeletions have been grouped together as a single clinical entity despite the fact that these deletions are variable in size and position depending on the Purpose: The five segmental duplications (LCR22-D to -H) at the distal region of chromosome 22 band q11.2 in the region immediately distal to the DiGeorge/velocardiofacial syndrome deleted region have been implicated in the recurrent distal 22q11.2 microdeletions.…”

Section: Introductionmentioning

confidence: 99%

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The recurrent distal 22q11.2 microdeletions are often de novo and do not represent a single clinical entity: a proposed categorization system

Mikhail

Burnside²,

Rush³

et al. 2014

Genetics in Medicine

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The recurrent distal 22q11.2 microdeletions are often de novo and do not represent a single clinical entity: a proposed categorization system

Mikhail

Burnside²,

Rush³

et al. 2014

Genetics in Medicine

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Are 22q11.2 distal deletions associated with math difficulties?

Carvalho

Vianna

Oliveira

et al. 2014

American J of Med Genetics Pt A

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Approximately 6% of school-aged children have math difficulties (MD). A neurogenetic etiology has been suggested due to the presence of MD in some genetic syndromes such as 22q11.2DS. However, the contribution of 22q11.2DS to the MD phenotype has not yet been investigated. This is the first population-based study measuring the frequency of 22q11.2DS among school children with MD. Children (1,564) were identified in the schools through a screening test for language and math. Of these children, 152 (82 with MD and 70 controls) were selected for intelligence, general neuropsychological, and math cognitive assessments and for 22q11.2 microdeletion screening using MLPA. One child in the MD group had a 22q11.2 deletion spanning the LCR22-4 to LCR22-5 interval. This child was an 11-year-old girl with subtle anomalies, normal intelligence, MD attributable to number sense deficit, and difficulties in social interactions. Only 19 patients have been reported with this deletion. Upon reviewing these reports, we were able to characterize a new syndrome, 22q11.2 DS (LCR22-4 to LCR22-5), characterized by prematurity; pre- and postnatal growth restriction; apparent hypotelorism, short/upslanting palpebral fissures; hypoplastic nasal alae; pointed chin and nose; posteriorly rotated ears; congenital heart defects; skeletal abnormalities; developmental delay, particularly compromising the speech; learning disability (including MD, in one child); intellectual disability; and behavioral problems. These results suggest that 22q11.2 DS (LCR22-4 to LCR22-5) may be one of the genetic causes of MD.

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Central 22q11.2 deletions

Rump

Leeuw

Essen

et al. 2014

American J of Med Genetics Pt A

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22q11.2 deletion syndrome is one of the most common microdeletion syndromes. Most patients have a deletion resulting from a recombination of low copy repeat blocks LCR22-A and LCR22-D. Loss of the TBX1 gene is considered the most important cause of the phenotype. A limited number of patients with smaller, overlapping deletions distal to the TBX1 locus have been described in the literature. In these patients, the CRKL gene is deleted. Haploinsufficiency of this gene has also been implicated in the pathogenesis of 22q11.2 deletion syndrome. To distinguish these deletions (comprising the LCR22-B to LCR22-D region) from the more distal 22q11.2 deletions (located beyond LCR22-D), we propose the term "central 22q11.2 deletions". In the present study we report on 27 new patients with such a deletion. Together with information on previously published cases, we review the clinical findings of 52 patients. The prevalence of congenital heart anomalies and the frequency of de novo deletions in patients with a central deletion are substantially lower than in patients with a common or distal 22q11.2 deletion. Renal and urinary tract malformations, developmental delays, cognitive impairments and behavioral problems seem to be equally frequent as in patients with a common deletion. None of the patients had a cleft palate. Patients with a deletion that also encompassed the MAPK1 gene, located just distal to LCR22-D, have a different and more severe phenotype, characterized by a higher prevalence of congenital heart anomalies, growth restriction and microcephaly. Our results further elucidate genotype-phenotype correlations in 22q11.2 deletion syndrome spectrum.

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Heart defects and other features of the 22q11 distal deletion syndrome

Cited by 32 publications

References 50 publications

The recurrent distal 22q11.2 microdeletions are often de novo and do not represent a single clinical entity: a proposed categorization system

The recurrent distal 22q11.2 microdeletions are often de novo and do not represent a single clinical entity: a proposed categorization system

Are 22q11.2 distal deletions associated with math difficulties?

Central 22q11.2 deletions

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