A new syndrome with noncompaction cardiomyopathy, bradycardia, pulmonary stenosis, atrial septal defect and heterotaxy with suggestive linkage to chromosome 6p

Wessels, Marja W.; Graaf, Bianca M. de; Cohen–Overbeek, Titia E.; Spitaels, Silja; Laat, Lotte E. de Groot–de; Cate, Folkert J. ten; Frohn-Mulder, Ingrid; Krijger, Ronald R. de; Bartelings, Margot M.; Essed, Nienke; Wladimiroff, J. W.; Niermeijer, Martinus F.; Heutink, Peter; Oostra, Ben A.; Dooijes, Dennis; Bertoli‐Avella, Aida M.; Willems, Patrick J.

doi:10.1007/s00439-007-0436-x

Cited by 38 publications

(30 citation statements)

References 48 publications

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“…Indeed, rhythm and conduction disturbances have been described in patients with confirmed left isomerism without structural cardiac defects. 24,25 Taken together, the spectrum of CHD in this family is compatible with that seen in left isomerism. Importantly, we could not confirm signs of left isomerism outside the heart (eg, polysplenia) in the investigated family members, although imaging of the abdomen and lungs was not available in all subjects, so we cannot rule out laterality defects in every individual.…”

Section: Discussionsupporting

confidence: 66%

A novel autosomal dominant condition consisting of congenital heart defects and low atrial rhythm maps to chromosome 9q

et al. 2011

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Congenital heart defects (CHDs) occur mostly sporadic, but familial CHD cases have been reported. Mutations in several genes, including NKX2.5, GATA4 and NOTCH1, were identified in families and patients with CHD, but the mechanisms underlying CHD are largely unknown. We performed genome-wide linkage analysis in a large four-generation family with autosomal dominant CHD (including atrial septal defect type I and II, tetralogy of Fallot and persistent left superior vena cava) and low atrial rhythm, a unique phenotype that has not been described before. We obtained phenotypic information including electrocardiography, echocardiography and DNA of 23 family members. Genome-wide linkage analysis on 12 affected, 5 unaffected individuals and 1 obligate carrier demonstrated significant linkage only to chromosome 9q21-33 with a multipoint maximum LOD score of 4.1 at marker D9S1690, between markers D9S167 and D9S1682. This 48-cM critical interval corresponds to 39 Mb and contains 402 genes. Sequence analysis of nine candidate genes in this region (INVS, TMOD1, TGFBR1, KLF4, IPPK, BARX1, PTCH1, MEGF9 and S1PR3) revealed no mutations, nor were genomic imbalances detected using array comparative genomic hybridization. In conclusion, we describe a large family with CHD and low atrial rhythm with a significant LOD score to chromosome 9q. The phenotype is representative of a mild form of left atrial isomerism or a developmental defect of the sinus node and surrounding tissue. Because the mechanisms underlying CHD are largely unknown, this study represents an important step towards the discovery of genes implied in cardiogenesis.

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Section: Discussionsupporting

confidence: 66%

A novel autosomal dominant condition consisting of congenital heart defects and low atrial rhythm maps to chromosome 9q

et al. 2011

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“…47–49 Further, this region (6p24.3-21.2) has been linked to a rare autosomal dominant syndrome that includes heart anomalies (non-compaction of the ventricular myocardium, bradycardia, pulmonary valve stenosis, secundum atrial septal defect, left isomerism, heterotaxy). 50 Thus, in silico data neither negates nor defines the potential contribution of this statistically associated SNP to disease risk.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Studies and Meta-Analyses for Congenital Heart Defects

Agopian

Goldmuntz

Hákonarson

et al. 2017

Circ Cardiovasc Genet

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Background Maternal and inherited (i.e., case) genetic factors likely contribute to the etiology of congenital heart defects, but it is unclear whether individual common variants confer a large risk. Methods and Results To evaluate the relationship between individual common maternal/inherited genotypes and risk for heart defects, we conducted genome-wide association studies (GWAS) in five cohorts. Three cohorts were recruited at the Children’s Hospital of Philadelphia: 670 conotruncal heart defect (CTD) case-parent trios; 317 left ventricular obstructive tract defect (LVOTD) case-parent trios; and 406 CTD cases and 2,976 pediatric controls. Two cohorts were recruited through the Pediatric Cardiac Genomics Consortium: 355 CTD trios and 192 LVOTD trios. We also conducted meta-analyses using the GWAS results from the CTD cohorts, the LVOTD cohorts and from the combined CTD and LVOTD cohorts. In the individual GWAS, several genome-wide significant associations (p≤5×10−8) were observed. In our meta-analyses, one genome-wide significant association was detected: the case genotype for rs72820264, an intra-genetic SNP associated with LVOTDs (p=2.1×10−8). Conclusions We identified one novel candidate region associated with LVOTDs and report on several additional regions with suggestive evidence for association with CTD and/or LVOTD. These studies were constrained by the relatively small samples sizes and thus have limited power to detect small to moderate associations. Approaches that minimize the multiple testing burden (e.g. gene- or pathway-based) may, therefore, be required to uncover common variants contributing to the risk of these relatively rare conditions.

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“…Algunos genes se han visto asociados con heterotaxia en humanos, como ZIC3, LEFTYA, NODAL y ACVR2B, entre otros. De igual manera, se han informado mutaciones en CRELD1 y se ha visto una posible asociación con el cromosoma 6p21 36 .…”

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Apendicitis aguda en paciente adulto con rotación intestinal anormal y defecto cardiovascular: presentación de caso y revisión temática

et al. 2018

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Citar como:. Villabona AN, Sorzano LI, Rodríguez HM, Espinosa LA, Villabona SA. Apendicitis aguda en paciente adulto con rotación intestinal anormal y defecto cardiovascular: presentación de caso y revisión temática. Rev Colomb Cir. 2018;33:220. https ResumenLa apendicitis aguda es la enfermedad quirúrgica que se presenta con mayor frecuencia en los servicios de urgencias. Su diagnóstico es predominantemente clínico; alrededor de dos terceras partes de los pacientes con apendicitis presentan un dolor típico localizado en el cuadrante inferior derecho. Sin embargo, hay manifestaciones atípicas, infrecuentes, como el dolor en el cuadrante inferior izquierdo. Se hace pues, importante conocer la existencia de ciertas enfermedades que puedan explicar estos síntomas para así tenerlas en cuenta en el momento de abordar un paciente con dolor abdominal. Estas son la rotación intestinal anormal y, con mayor frecuencia, el situs inversus, que explican el dolor abdominal secundario a la apendicitis en una localización diferente a la clásica para hacer el diagnóstico y dar tratamiento oportuno, con el fin de prevenir complicaciones. Además, los estudios complementarios son importantes en estos pacientes para descartar otras alteraciones o malformaciones, como defectos cardiovasculares, los que se han relacionado con anomalías en la formación y la rotación gastrointestinal en 27 % de los casos, aproximadamente. Se presenta el caso de hombre joven, con un cuadro clínico de dolor abdominal que se inició en el epigastrio y después se localizó en el cuadrante inferior izquierdo, acompañado de signos de irritación peritoneal y alteración de los exámenes paraclínicos. Los estudios de imagen confirmaron la presencia de rotación intestinal anormal y apendicitis aguda izquierda. Durante el seguimiento del paciente, se practicó una ecocardiografía transesofá-gica por dolor torácico, la cual demostró insuficiencia valvular aórtica secundaria a valvulopatía aórtica bivalva. Palabras clave: apendicitis; diagnóstico; apendicectomía; laparotomía; situs inversus; cardiopatías congénitas. AbstractAcute appendicitis is the most frequent surgical pathology at the emergency departments and its diagnosis is predominantly clinical. Around 2/3 of the patients with this pathology present typical pain, located in the right lower quadrant. However, abdominal pain in the left lower quadrant secondary to acute appendicitis is of

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A new syndrome with noncompaction cardiomyopathy, bradycardia, pulmonary stenosis, atrial septal defect and heterotaxy with suggestive linkage to chromosome 6p

Cited by 38 publications

References 48 publications

A novel autosomal dominant condition consisting of congenital heart defects and low atrial rhythm maps to chromosome 9q

A novel autosomal dominant condition consisting of congenital heart defects and low atrial rhythm maps to chromosome 9q

Genome-Wide Association Studies and Meta-Analyses for Congenital Heart Defects

Apendicitis aguda en paciente adulto con rotación intestinal anormal y defecto cardiovascular: presentación de caso y revisión temática

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