Cantu syndrome: A longitudinal review of vascular findings in three individuals

Parrott, Ashley; Lombardo, Rachel C.; Brown, Nicole M.; Tretter, Justin T.; Riley, Laura E.; Weaver, K. Nicole

doi:10.1002/ajmg.a.61521

Cited by 9 publications

(10 citation statements)

References 22 publications

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“…We did not find an enrichment of previously described Mendelian thoracic aortic aneurysm and dissection genes 49 (23 genes; 2 overlapping with ascending loci, P = 0.14; 1 overlapping with descending loci, P = 0.32 by one-tailed permutation tests). However, our analysis has independently identified loci containing relevant genes such as FBN1 , well described as the causal gene in Marfan syndrome 50 , and loci near genes such as PI15, known to cause arterial dysfunction in rats 51 , as well as the ABCC9-KCNJ8 locus, linked to Cantú syndrome—a rare recessive cause of aortic aneurysm in humans 52 . Other loci suggest the involvement of novel genes within networks previously implicated in aortic disease; for instance, the protein product of ASB2 is part of the E3 ligase that targets both filamin B (encoded by FLNB, the nearest gene to a lead SNP on chromosome 3) and the known aortic disease protein filamin A ( FLNA ) for degradation 53 .…”

Section: Resultsmentioning

confidence: 99%

Deep learning enables genetic analysis of the human thoracic aorta

et al. 2021

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Enlargement or aneurysm of the aorta predisposes to dissection, an important cause of sudden death. We trained a deep learning model to evaluate the dimensions of the ascending and descending thoracic aorta in 4.6 million cardiac magnetic resonance images from the UK Biobank. We then conducted genome-wide association studies in 39,688 individuals, identifying 82 loci associated with ascending and 47 with descending thoracic aortic diameter, of which 14 loci overlapped. Transcriptome-wide analyses, rare-variant burden tests, and human aortic single nucleus RNA sequencing prioritized genes including SVIL , which was strongly associated with descending aortic diameter. A polygenic score for ascending aortic diameter was associated with thoracic aortic aneurysm in 385,621 UK Biobank participants (HR = 1.43 per s.d.; CI 1.32-1.54; P = 3.3 × 10 −20 ). Our results illustrate the potential for rapidly defining quantitative traits with deep learning, an approach that can be broadly applied to biomedical images.

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Section: Resultsmentioning

confidence: 99%

Deep learning enables genetic analysis of the human thoracic aorta

et al. 2021

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“…It can also be a consequence of arteriovenous shunting, either naturally occurring or iatrogenic, as in AV fistulae introduced for renal dialysis. 43–45 Both peripheral vasodilation and AV shunts are observed in CS, 3 , 4 , 46 and thus we suggest that increased vascular K + channel activity may be an unrecognized basis for HOHF. Heart failure with increased cardiac output appears oxymoronic and what exactly is “failing” in HOHF remains poorly defined.…”

Section: Discussionmentioning

confidence: 73%

The Mechanism of High-Output Cardiac Hypertrophy Arising From Potassium Channel Gain-of-Function in Cantú Syndrome

et al. 2020

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Dramatic cardiomegaly arising from gain-of-function (GoF) mutations in the ATP-sensitive potassium (KATP) channels genes, ABCC9 and KCNJ8, is a characteristic feature of Cantú Syndrome (CS). How potassium channel over-activity results in cardiac hypertrophy, as well as the long-term consequences of CV remodeling in CS, is unknown. Using genome-edited mouse models of CS, we sought to dissect the pathophysiological mechanisms linking KATP channel GoF to cardiac remodeling. We demonstrate that chronic reduction of systemic vascular resistance in CS is accompanied by elevated renin-angiotensin signaling, which drives cardiac enlargement and blood volume expansion. Cardiac enlargement in CS results in elevation of basal cardiac output, which is preserved in aging. However, the cardiac remodeling includes altered gene expression patterns that are associated with pathological hypertrophy and is accompanied by decreased exercise tolerance, suggestive of reduced cardiac reserve. Our results identify a high-output cardiac hypertrophy phenotype in CS which is etiologically and mechanistically distinct from other myocardial hypertrophies, and which exhibits key features of high-output heart failure (HOHF). We propose that CS is a genetically-defined HOHF disorder and that decreased vascular smooth muscle excitability is a novel mechanism for HOHF pathogenesis.

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“…Cardiovascular involvement is frequently reported in individuals with Cantu syndrome and can include cardiomegaly, pulmonary hypertension, pericardial effusion, dilated and tortuous blood vessels and congenital heart defects [ 12 ]. Cardiomegaly in Cantu syndrome is characterized by ventricular enlargement with preserved or increased systolic function (high output state) in which muscle function and histology are typically normal [ 9 , 13 ].…”

Section: Discussionmentioning

confidence: 99%

Multiple vascular anomalies and refractory pericardial effusion in a young patient with Cantu syndrome: a case report and review of the literature

Daas,

Gupta,

Kiblawi

2023

BMC Pediatr

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Background Cantu syndrome is a rare and complex multisystem disorder characterized by hypertrichosis, facial dysmorphism, osteochondroplasia and cardiac abnormalities. With only 150 cases reported worldwide, Cantu syndrome is now gaining wider recognition due to molecular testing and a growing body of literature that further characterizes the syndrome and some of its most important features. Cardiovascular pathology previously described in the literature include cardiomegaly, pericardial effusion, vascular dilation and tortuosity, and other congenital heart defects. However, cardiovascular involvement is highly variable amongst individuals with Cantu syndrome. In some instances, it can be extensive and severe requiring surgical management and long term follow up. Case presentation Herein we report a case of a fourteen-year-old female who presented with worsening pericardial effusion of unknown etiology, and echocardiographic findings of concentric left ventricular hypertrophy, a mildly dilated aortic root and ascending aorta. Her medical history was notable for hemoptysis and an episode of pulmonary hemorrhage secondary to multiple aortopulmonary collaterals that were subsequently embolized in early childhood. She was initially managed with Ibuprofen and Colchicine but continued to worsen, and ultimately required a pericardial window for the management of refractory pericardial effusion. Imaging studies obtained on subsequent visits revealed multiple dilated and tortuous blood vessels in the head, neck, chest, and pelvis. A cardiomyopathy molecular studies panel was sent, and a pathogenic variant was identified in the ABCC9 gene, confirming the molecular diagnosis of autosomal dominant Cantu syndrome. Conclusions Vascular anomalies and significant cardiac involvement are often present in Cantu syndrome, however there are currently no established screening recommendations or surveillance protocols in place. The triad of hypertrichosis, facial dysmorphism, and unexplained cardiovascular involvement in any patient should raise suspicion for Cantu syndrome and warrant further investigation. Initial cardiac evaluation and follow up should be indicated in any patient with a clinical and/or molecular diagnosis of Cantu syndrome. Furthermore, whole body imaging should be utilized to evaluate the extent of vascular involvement and dictate long term monitoring and care.

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Cantu syndrome: A longitudinal review of vascular findings in three individuals

Cited by 9 publications

References 22 publications

Deep learning enables genetic analysis of the human thoracic aorta

Deep learning enables genetic analysis of the human thoracic aorta

The Mechanism of High-Output Cardiac Hypertrophy Arising From Potassium Channel Gain-of-Function in Cantú Syndrome

Multiple vascular anomalies and refractory pericardial effusion in a young patient with Cantu syndrome: a case report and review of the literature

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