The Cardiac Phenotype in Patients With a
            <i>CHD7</i>
            Mutation

Corsten‐Janssen, Nicole; Kerstjens-Frederikse, Wilhelmina S.; Sarvaas, Gideon J. du Marchie; Baardman, Maria E.; Bakker, Marian K.; Bergman, Jorieke E. H.; Hove, Hanne; Heimdal, Ketil; Rustad, Cecilie F.; Hennekam, Raoul C. M.; Hofstra, Robert; Hoefsloot, Lies H.; Ravenswaaij-Arts, Conny M. A. van; Kapusta, Livia

doi:10.1161/circgenetics.113.000054

Cited by 65 publications

(71 citation statements)

References 37 publications

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“…Congenital heart defects occur in 74% of patients who have CHARGE syndrome due to a CHD7 mutation, and in 80% of patients with a truncating CHD7 mutation [3]. Our previous study showed that while the types of heart defects found in CHARGE syndrome patients are variable, atrioventricular septal defects and conotruncal defects are overrepresented compared to typically non-syndromic heart defects [3].…”

Section: Introductionmentioning

confidence: 96%

Congenital arch vessel anomalies in CHARGE syndrome: A frequent feature with risk for co-morbidity

Corsten‐Janssen

Ravenswaaij-Arts

Kapusta

2016

IJC Heart & Vasculature

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BackgroundCHARGE syndrome is a complex multiple congenital malformation disorder with variable expression that is caused by mutations in the CHD7 gene. Variable heart defects occur in 74% of patients with a CHD7 mutation, with an overrepresentation of atrioventricular septal defects and conotruncal defects — including arch vessel anomalies.Methods and resultsWe report an index patient with an arch vessel anomaly underlying serious feeding problems that resolved after arch vessel surgery. This led us to examine the incidence of arch vessel anomalies in our previously studied cohort of 299 patients with a CHD7 mutation. Forty-two patients (14%) had an aortic arch anomaly, mostly aberrant subclavian artery or right aortic arch, which usually occurred in combination with other congenital heart defects (81%). The majority of these patients also had feeding problems that may be linked to their arch anomaly, but insufficient information was available to exclude other causes.ConclusionsArch vessel anomalies occur in a significant proportion of patients with a CHD7 mutation, and these anomalies may cause morbidity due to compression of the esophagus or trachea. Since symptoms of vascular compression can mimic those caused by other abnormalities in CHARGE syndrome, it is important to be aware of arch vessel anomalies in this complex patient category. Whether a solitary arch vessel anomaly is an indicator for CHARGE syndrome still needs to be studied, but doctors should look out for other CHARGE syndrome features in patients with arch vessel anomalies.

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Section: Introductionmentioning

confidence: 96%

Congenital arch vessel anomalies in CHARGE syndrome: A frequent feature with risk for co-morbidity

Corsten‐Janssen

Ravenswaaij-Arts

Kapusta

2016

IJC Heart & Vasculature

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“…The severity and spectrum of congenital heart defects had been thought to vary [9]. It is recently reported that conotruncal defects and atrioventricular septal defects are overrepresented in patients with CHD7 mutations compared with patients with nonsyndromic heart defects [10]. Tetralogy of Fallot was relatively frequent among the conotruncal defects, whereas interrupted aortic arch, double outlet right ventricle, and truncus arteriosus were less frequently seen.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Malformations in CHARGE Syndrome with DiGeorge Phenotype: Two Case Reports

Yasuda

Morihana

Fusazaki

et al. 2016

Case Reports in Pediatrics

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Both CHARGE syndrome and DiGeorge anomaly are frequently accompanied by cardiovascular malformations. Some specific cardiovascular malformations such as interrupted aortic arch type B and truncus arteriosus are frequently associated with 22q11.2 deletion syndrome, while conotruncal defects and atrioventricular septal defects are overrepresented in patients with CHARGE syndrome. CHD7 gene mutation is identified in approximately two-thirds of patients with CHARGE syndrome, and chromosomal microdeletion at 22q11.2 is found in more than 95% of patients with 22q11.2 deletion syndrome. CHARGE syndrome is occasionally accompanied by DiGeorge phenotype. We report two patients with dysmorphic features of both CHARGE syndrome and 22q11.2 deletion syndrome. Although both of the two cases did not have 22q11.2 deletion, they had typical dysmorphic features of 22q11.2 deletion syndrome including cardiovascular malformations such as interrupted aortic arch type B. They also had characteristic features of CHARGE syndrome including ear malformation, genital hypoplasia, limb malformation, and endocrinological disorders. CHD7 gene mutation was confirmed in one of the two cases. When a patient with cardiovascular malformations frequently associated with 22q11.2 deletion syndrome does not have 22q11.2 deletion, we suggest that associated malformations characteristic of CHARGE syndrome should be searched for.

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“…Since CHD7 causes congenital heart defects in most people harboring a pathogenic CHD7 mutation (Corsten-Janssen et al, 2013), several studies have analyzed CHD7 in cohorts of patients with cardiovascular malformations and an overview of these studies is shown in Table 1. Screening of only CHD7 in a cohort of 67 patients with isolated heart defects (Qi et al, 2008) and in a cohort of 46 patients selected for their type of heart defect and one other feature of CHARGE syndrome (Corsten-Janssen et al, 2014) identified no pathogenic mutations.…”

Section: Chd7 Mutations In Cohorts Of Patients With Heart Defectsmentioning

confidence: 99%

“…The combination of AVSD, outflow tract defects and PDA encompasses about 52% of the heart defects in the CHD7 mutation group but these defects represent only 12% in the non-syndromic group. Figure adapted from (Corsten-Janssen et al, 2013). AVSD, atrioventricular septal defects; LVOTO, left ventricular outflow tract obstruction; OFT, outflow tract defects; PDA, patent ductus arteriosus; RVOTO, right ventricular outflow tract obstruction major CHARGE feature.…”

Section: Chd7 Mutations In Cohorts Of Patients With Heart Defectsmentioning

confidence: 99%

“…As shown in Figure 1, an overrepresentation of AVSD, PDA and outflow tract defects was seen in patients with a CHD7 mutation as compared to a group of non-syndromic heart malformations (Corsten-Janssen et al, 2013). Aortic arch anomalies were also frequently present in the cohort, including abnormal branching such as aberrant subclavian artery (Corsten-Janssen, van Ravenswaaij-Arts, & Kapusta, 2016).…”

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confidence: 93%

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Clinical and molecular effects of CHD7 in the heart

Corsten‐Janssen

Scambler

2017

American J of Med Genetics Pt C

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Heart defects caused by loss-of-function mutations in CHD7 are a frequent cause of morbidity and mortality in CHARGE syndrome. Here we review the clinical and molecular aspects of CHD7 that are related to the cardiovascular manifestations of the syndrome. The types of heart defects found in patients with CHD7 mutations are variable, with an overrepresentation of atrioventricular septal defect and outflow tract defect including aortic arch anomalies compared to nonsyndromic heart defects. Chd7 haploinsufficiency in mouse is a good model for studying the heart effects seen in CHARGE syndrome, and mouse models reveal a role for Chd7 in multiple lineages during heart development. Formation of the great vessels requires Chd7 expression in the pharyngeal surface ectoderm, and this expression likely has an non-autonomous effect on neural crest cells. In the cardiogenic mesoderm, Chd7 is required for atrioventricular cushion development and septation of the outflow tract. Emerging knowledge about the function of CHD7 in the heart indicates that it may act in concert with transcription factors such as TBX1 and SMADs to regulate genes such as p53 and the cardiac transcription factor NKX2.5.

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The Cardiac Phenotype in Patients With a CHD7 Mutation

Cited by 65 publications

References 37 publications

Congenital arch vessel anomalies in CHARGE syndrome: A frequent feature with risk for co-morbidity

Congenital arch vessel anomalies in CHARGE syndrome: A frequent feature with risk for co-morbidity

Cardiovascular Malformations in CHARGE Syndrome with DiGeorge Phenotype: Two Case Reports

Clinical and molecular effects of CHD7 in the heart

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