Phenotypes, pleiotropy, and phylogeny

Opitz, John M.

doi:10.1002/ajmg.c.31574

Cited by 6 publications

(5 citation statements)

References 42 publications

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“…Similarly to conotruncal heart defects in the context of 22q11.2 deletion syndrome and branchial arch anomalies, AVCD can be considered as a phenotypic marker linking all syndromes related to cilia through Shh pathway. Hence, we postulate that AVCD should be considered as part of "developmental field" as introduced by Opitz et al [134,135].…”

Section: Discussionmentioning

confidence: 96%

Genetics of atrioventricular canal defects

et al. 2020

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Atrioventricular canal defect (AVCD) represents a quite common congenital heart defect (CHD) accounting for 7.4% of all cardiac malformations. AVCD is a very heterogeneous malformation that can occur as a phenotypical cardiac aspect in the context of different genetic syndromes but also as an isolated, non-syndromic cardiac defect. AVCD has also been described in several pedigrees suggesting a pattern of familiar recurrence. Targeted Next Generation Sequencing (NGS) techniques are proved to be a powerful tool to establish the molecular heterogeneity of AVCD. Given the complexity of cardiac embryology, it is not surprising that multiple genes deeply implicated in cardiogenesis have been described mutated in patients with AVCD. This review attempts to examine the recent advances in understanding the molecular basis of this complex CHD in the setting of genetic syndromes or in nonsyndromic patients.

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Section: Discussionmentioning

confidence: 96%

Genetics of atrioventricular canal defects

et al. 2020

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“…Similarly to that occurring for conotruncal heart defects in deletion 22q11.2 syndrome and branchial arch anomalies, AVCD should be considered as the cardiac manifestation linking ciliopathy syndromes. AVCD could be part of a “developmental field,” accordingly to the concept that malformations can be due to defects in signal transduction cascades or pathways in developmental field defects . The single morphogenetic unit may be altered by Mendelian mutations, aneuploidies, and environmental causes.…”

Section: Discussionmentioning

confidence: 99%

“…It involves a progenitor and secondary fields, and it is homologous to AVCD in related species who share corresponding structure due to descent with modification from a common ancestor. 115,116 Tissue of extracardiac origin, from the posterior segment of the SHF (the so-called DMP) is recognized as a fundamental component of atrial and atrioventricular septation of the heart. [8][9][10]117 Cells of the DMP growing toward the primary atrial septum fuse with the posteroinferior and anterosuperior atrioventricular cushions to close the primary atrial foramen and to form 2 separate atrioventricular valves.…”

Section: Pathogenetic Mechanism Of Avcd: the Role Of Shhmentioning

confidence: 99%

“…AVCD could be part of a "developmental field," accordingly to the concept that malformations can be due to defects in signal transduction cascades or pathways in developmental field defects. 115,116 The single morphogenetic unit may be altered by Mendelian mutations, aneuploidies, and environmental causes.…”

Section: Pathogenetic Mechanism Of Avcd: the Role Of Shhmentioning

confidence: 99%

“…Non‐syndromic AVCD is a CHD with genetic heterogeneity. It involves a progenitor and secondary fields, and it is homologous to AVCD in related species who share corresponding structure due to descent with modification from a common ancestor . Tissue of extracardiac origin, from the posterior segment of the SHF (the so‐called DMP) is recognized as a fundamental component of atrial and atrioventricular septation of the heart .…”

Section: Atrioventricular Canal Defectmentioning

confidence: 99%

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Atrioventricular canal defect and genetic syndromes: The unifying role of sonic hedgehog

et al. 2018

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The atrioventricular canal defect (AVCD) is a congenital heart defect (CHD) frequently associated with extracardiac anomalies (75%). Previous observations from a personal series of patients with AVCD and "polydactyly syndromes" showed that the distinct morphology and combination of AVCD features in some of these syndromes is reminiscent of the cardiac phenotype found in heterotaxy, a malformation complex previously associated with functional cilia abnormalities and aberrant Hedgehog (Hh) signaling. Hh signaling coordinates multiple aspects of left-right lateralization and cardiovascular growth. Being active at the venous pole the secondary heart field (SHF) is essential for normal development of dorsal mesenchymal protrusion and AVCD formation and septation. Experimental data show that perturbations of different components of the Hh pathway can lead to developmental errors presenting with partially overlapping manifestations and AVCD as a common denominator. We review the potential role of Hh signaling in the pathogenesis of AVCD in different genetic disorders. AVCD can be viewed as part of a "developmental field," according to the concept that malformations can be due to defects in signal transduction cascades or pathways, as morphogenetic units which may be altered by Mendelian mutations, aneuploidies, and environmental causes.

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