Spectrum of clinical variability in familial deletion 22q11.2: from full manifestation to extremely mild clinical anomalies

Digilio, M. Cristina; Angioni, Adriano; Santis, M De; Lombardo, Antonietta; Giannotti, Aldo; Dallapiccola, Bruno; Marino, Bruno

doi:10.1034/j.1399-0004.2003.00049.x

Cited by 113 publications

(105 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…48 The most common features include cardiovascular anomalies, palate anomalies, feeding disorders, speech and learning disabilities, renal anomalies, and behavioral disorders. Other abnormalities may include hypocalcemia, immunodeficiency, skeletal abnormalities, and growth hormone deficiency.…”

Section: Loci and Genes Associated With Congenital Heart Defects Idenmentioning

confidence: 99%

Genetic Basis for Congenital Heart Defects: Current Knowledge

Pierpont¹,

Basson²,

Benson³

et al. 2007

Circulation

750

377

View full text Add to dashboard Cite

Abstract-The intent of this review is to provide the clinician with a summary of what is currently known about the contribution of genetics to the origin of congenital heart disease. Techniques are discussed to evaluate children with heart disease for genetic alterations. Many of these techniques are now available on a clinical basis. Information on the genetic and clinical evaluation of children with cardiac disease is presented, and several tables have been constructed to aid the clinician in the assessment of children with different types of heart disease. Genetic algorithms for cardiac defects have been constructed and are available in an appendix. It is anticipated that this summary will update a wide range of medical personnel, including pediatric cardiologists and pediatricians, adult cardiologists, internists, obstetricians, nurses, and thoracic surgeons, about the genetic aspects of congenital heart disease and will encourage an interdisciplinary approach to the child and adult with congenital heart disease. (Circulation. 2007;115:3015-3038.)

show abstract

Section: Loci and Genes Associated With Congenital Heart Defects Idenmentioning

confidence: 99%

Genetic Basis for Congenital Heart Defects: Current Knowledge

Pierpont¹,

Basson²,

Benson³

et al. 2007

Circulation

750

377

View full text Add to dashboard Cite

show abstract

“…These include the hemizygosity of the 45 genes in the 22q11.2 deletion region and interaction of the effects of hemizygosity with genetic variants both in the intact chromosome 22 and elsewhere in the genome. 8,9 In families of probands with 22q11.2 deletions, an elevated prevalence of CHD in relatives without 22q11.2 deletions would support this hypothesis of genetic interaction. Two previous pediatric studies have suggested such an elevated prevalence of CHD.…”

mentioning

confidence: 57%

Complex Congenital Heart Disease in Unaffected Relatives of Adults With 22q11.2 Deletion Syndrome

Swaby

Silversides

Bekeschus

et al. 2011

The American Journal of Cardiology

View full text Add to dashboard Cite

The 22.q11.2 deletion syndrome (22q11DS) is a common genetic condition associated with 22q11.2 microdeletions and classically has included congenital heart disease (CHD) as a part of the variable expression. Some evidence has shown that relatives of those with 22q11DS might be at an increased risk of CHD in the absence of 22q11.2 deletions. We obtained a detailed family history of CHD in the first-to third-degree relatives (n = 2,639) of 104 adult probands with 22q11DS. We compared the prevalence of CHD in the relatives without 22q11.2 deletions to the published general population prevalence. We also investigated the effect of CHD in the probands on prevalence of CHD in the relatives. Of the 104 probands with 22q11DS, 14 (13.5%) had 17 relatives (17 of 2,639, 0.6%) with CHD. Of 66 probands with CHD, 15 (0.9%) of their 1,663 relatives had CHD, a significantly greater prevalence than that for the relatives of probands without CHD (0.2%, 2 of 976, p = 0.041, odds ratio 4.43, 95% confidence interval 1.03 to 40.00). In relatives of probands with CHD, the prevalence of those with severe CHD (0.36%) was significantly elevated compared to population expectations (0.061%, p = 0.007, odds ratio 5.88, 95% confidence interval 2.16 to 12.85). In conclusion, these results support a heritable susceptibility to CHD in families of probands with 22q11DS, in addition to that imparted by microdeletion 22q11.2. The occurrence of CHD in relatives might be related to the expression of CHD in the proband with 22q11DS. These findings have potential implications for the genetic counseling of families of those with 22q11DS and support the notion that interacting genetic variants might contribute to the variable expression of 22q11DS.The 22q11.2 deletion syndrome (22q11DS) is a common, multisystem disorder associated with microdeletion 22q11.2 that occurs at an estimated prevalence of 1/4,000 live births.1 Congenital heart disease (CHD) is a classic feature of 22q11.2DS, found in about 40% of patients.2-5 Conotruncal anomalies such as tetralogy of Fallot (TOF), interrupted aortic arch, and truncus arteriosus have been most strongly associated.6,7 Multiple factors are CIHR Author Manuscript CIHR Author Manuscript CIHR Author Manuscriptthought to affect the expression of CHD in patients with 22q11DS. These include the hemizygosity of the 45 genes in the 22q11.2 deletion region and interaction of the effects of hemizygosity with genetic variants both in the intact chromosome 22 and elsewhere in the genome.8,9 In families of probands with 22q11.2 deletions, an elevated prevalence of CHD in relatives without 22q11.2 deletions would support this hypothesis of genetic interaction. Two previous pediatric studies have suggested such an elevated prevalence of CHD.10,11 However these studies involved in total just 6 first-degree relatives with CHD and did not report on the parental origin of the 22q11.2 deletion. In the present study, a wellcharacterized group of adults with 22q11DS was examined for a family history of CHD in their relatives...

show abstract

“…Shprintzen after 30 years of study of the anomaly wrote that del22 syndrome has a wide spectrum of phenotypes with more than 180 clinical manifestations that involve essentially every organ (3), and also found that different dysmorphic features can be seen in different racial groups and different ages (4) and even in one and the same family (2,4). In this way, the spectrum of associated involvements becomes wider (5). According to Marino et al, cardiovascular malformations are always present in these patients (6).…”

mentioning

confidence: 99%