DiGeorge syndrome with isolated aortic coarctation and isolated ventricular septal defect in three sibs with a 22q11 deletion of maternal origin.

Wilson, D.I.; Cross, I; Goodship, Judith A.; Coulthard, Stanley W.; Carey, Alisoun H.; Scambler, Peter J.; Bain, H H; Hunter, A S; Carter, P E; Burn, John

doi:10.1136/hrt.66.4.308

Cited by 90 publications

(42 citation statements)

References 21 publications

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“…Cardiac involvement ranges from the incidental finding of a right aortic arch to severe low cardiac output from type B interrupted aortic arch. Even within one family, the variability may be as great as between unrelated individuals, as seen in the largest family described here and in smaller families [Wilson et al, 1991;Holder et al, 1993;McLean et al, 1993].…”

Section: Discussionmentioning

confidence: 92%

Evolution of latent hypoparathyroidism in familial 22q11 deletion syndrome

et al. 1997

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Latent hypoparathyroidism (LHP), the inability to increase midmolecular parathyroid hormone levels appropriately during a hypocalcemic challenge, was reported previously in an asymptomatic woman with tetralogy of Fallot. This women's fourth child died with DiGeorge anomaly. Seven years later, we restudied the index patient with LHP and evaluated three generations of her family for parathyroid dysfunction, cardiac abnormalities, and del 22(q11). Deletions were found in six relatives, three with conotruncal cardiac defects and three with a structurally normal heart. We found significant transgenerational noncardiac phenotypic variability, including learning difficulties, dysmorphic facial appearance, and psychiatric illness. A spectrum of parathyroid gland dysfunction associated with the del 22(q11) was seen, ranging from hypocalcemic hypoparathyroidism to normocalcemia with abnormally low basal intact parathyroid hormone (iPTH) levels. In addition, LHP found in the index patient 7 years ago had evolved to frank hypocalcemic hypoparathyroidism. In this family, which is the largest family with 22q11 deletions studied to date, parathyroid gland dysfunction evolved over time. We suggest that the calcium parathyroid hormone axis of unrelated patients with del 22(q11) be followed closely for the development of hypocalcemic hypoparathyroidism.

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Section: Discussionmentioning

confidence: 92%

Evolution of latent hypoparathyroidism in familial 22q11 deletion syndrome

et al. 1997

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“…Although many cases of these syndromes are closely linked to deletions in chromosome 22qI 1 (36)(37)(38), no causative genes are identified. The manifestations of these syndromes are quite similar to the phenotype of Edn -'-homozygotes.…”

Section: Discussionmentioning

confidence: 99%

“…In human diseases, ventricular septal defect and aortic arch anomalies including type B aortic arch interruption are shown to be associated with or a part of congenital syndromes including Pierre-Robin syndrome (35), DiGeorge syndrome (36,37), and velo-cardio-facial syndrome (38), which involves craniofacial tissues and organs. Although many cases of these syndromes are closely linked to deletions in chromosome 22qI 1 (36)(37)(38), no causative genes are identified.…”

Section: Discussionmentioning

confidence: 99%

Aortic arch malformations and ventricular septal defect in mice deficient in endothelin-1.

Kurihara

Kurihara²,

Oda³

et al. 1995

J. Clin. Invest.

372

209

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Endothelin-1 (ET-1) is a 21-amino acid peptide with various biological activities including vasoconstriction and cell proliferation. To clarify the physiological and pathophysiological role of ET-1, we disrupted the mouse Edni locus encoding ET-1 by gene targeting and demonstrated that ET-1 is essential to the normal development of pharyngeal archderived tissues and organs. In this study, we focused on the phenotypic manifestations of EdnI -'-homozygous mice in the cardiovascular system. Edn -'-homozygotes display cardiovascular malformations including interrupted aortic arch (23% ), tubular hypoplasia of the aortic arch (4.6% ), aberrant right subclavian artery (12.9%), and ventricular septal defect with abnormalities of the outflow tract (48.4%). The frequency and extent of these abnormalities are increased by treatment with neutralizing monoclonal antibodies or a selective ETA receptor antagonist BQ123. At an earlier embryonic stage, formation of pharyngeal arch arteries and endocardial cushion is disturbed in Ednl-'-homozygotes. In situ hybridization confirmed ET-1 expression in the endothelium of the arch arteries and cardiac outflow tract and the endocardial cushion as well as in the epithelium of the pharyngeal arches. Thus, ET-1 is involved in the normal development of the heart and great vessels, and circulating ET-1 and/or other ET isoforms may cause a functional redundancy, at least partly, through the ETA receptor. (J. Clin. Invest. 1995. 96:293-300.)

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“…18 -21 However, we and others have reported marked phenotypic variability associated with the deletion, and we are in agreement with a recent letter to the editor by Liling et al suggesting that this variability raises the possibility of patients with "subclinical deletions" being more common than has been previously recognized. 10,13,[22][23][24] In fact, here we report the first cohort of unselected patients identified with the 22q11.2 deletion only fol-lowing the diagnosis in a relative. Their findings shed additional light on the variability of the disorder.…”

mentioning

confidence: 99%

Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: Cast a wide FISHing net!

McDonald‐McGinn

Tonnesen

Laufer-Cahana

et al. 2001

Genetics in Medicine

276

229

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Purpose: The chromosome 22q11.2 deletion has been identified in the majority of patients with DiGeorge syndrome, velocardiofacial syndrome, and conotruncal anomaly face syndrome and in some patients with the autosomal dominant Opitz G/BBB syndrome and Cayler cardiofacial syndrome. In addition, 22q11.2 deletion studies are becoming part of a standardized diagnostic workup for some isolated defects such as conotruncal cardiac anomalies and velopharyngeal incompetence. However, there is little information available on the clinical findings of unselected patients. For example, those individuals identified during prenatal diagnosis, as part of a generalized screening protocol, or following the diagnosis in a relative. This information will be invaluable in defining the variability of the disorder and in observing long-term outcome in the absence of targeted remediations. This study allows one to examine the first unselected cohort of patients and serves to highlight the importance of deletion testing in parents of affected probands. Methods: Thirty individuals with a 22q11.2 deletion were identified following the diagnosis in a relative. Nineteen were adults ascertained only following the diagnosis in their child, 10 were children identified following the diagnosis in their sibling, and one was a child diagnosed prenatally following the diagnosis in her parent. Results:Sixty percent of patients had no visceral anomalies. In fact, only 6 of the 19 adults (32%) and 6 of the 11 children (55%) had major findings which would have brought them to medical attention. Deletion sizing demonstrated the same large 3-4MB deletion in most families despite wide inter and intrafamilial variability and there was no difference in clinical findings based on the parent of origin. Thus, no genotype-phenotype correlations could be made. Conclusion: We report the first unselected cohort of patients with the 22q11.2 deletion identified through an affected relative. Analysis of this series of 30 patients, many with very mild manifestations of the deletion, allows one to examine the outcome in individuals who lacked specific remediations for this disorder. It emphasizes the importance of broadening the index of suspicion in order to provide appropriate recurrence risk counseling, cognitive remediation, and medical management.Further, it underscores the lack of familial concordance and the current lack of genotype-phenotype correlations in this disorder, and it raises the possibility that the deletion is more common than previously reported. Genetics in Medicine, 2001:3(1):23-29.

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DiGeorge syndrome with isolated aortic coarctation and isolated ventricular septal defect in three sibs with a 22q11 deletion of maternal origin.

Cited by 90 publications

References 21 publications

Evolution of latent hypoparathyroidism in familial 22q11 deletion syndrome

Evolution of latent hypoparathyroidism in familial 22q11 deletion syndrome

Aortic arch malformations and ventricular septal defect in mice deficient in endothelin-1.

Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: Cast a wide FISHing net!

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