Atrioventricular canal defect and genetic syndromes

The unifying role of sonic hedgehog

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish
JournalClinical Genetics
DOIs
Publication statusE-pub ahead of print - May 3 2018

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Signal Transduction
Polydactyly
Inborn Genetic Diseases
Congenital Heart Defects
Cilia
Aneuploidy
Atrioventricular Septal Defect
Phenotype
Mutation
Growth

Cite this

@article{0ca924ea87254417899479413d984fcd,
title = "Atrioventricular canal defect and genetic syndromes: The unifying role of sonic hedgehog",
abstract = "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.",
author = "Digilio, {M C} and F Pugnaloni and {De Luca}, A and G Calcagni and A Baban and Dentici, {M L} and P Versacci and B Dallapiccola and M Tartaglia and B Marino",
note = "{\circledC} 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",
year = "2018",
month = "5",
day = "3",
doi = "10.1111/cge.13375",
language = "English",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "Wiley-Blackwell Publishing Ltd",

}

TY - JOUR

T1 - Atrioventricular canal defect and genetic syndromes

T2 - The unifying role of sonic hedgehog

AU - Digilio, M C

AU - Pugnaloni, F

AU - De Luca, A

AU - Calcagni, G

AU - Baban, A

AU - Dentici, M L

AU - Versacci, P

AU - Dallapiccola, B

AU - Tartaglia, M

AU - Marino, B

N1 - © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2018/5/3

Y1 - 2018/5/3

N2 - 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.

AB - 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.

U2 - 10.1111/cge.13375

DO - 10.1111/cge.13375

M3 - Review article

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

ER -