Molecular genetics of pulmonary hypertension in children

Taha, Fatima; Southgate, Laura

doi:10.1016/j.gde.2022.101936

Cited by 5 publications

(3 citation statements)

References 67 publications

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“… 13 She is negative for other genetic mutations indicated as possible causes of PAH, including BMP9, SOX17, and TBX4 . 14 , 15 In addition to questions regarding screening of family members for BMPR2 mutation, the patient requests input into how the mutation itself could potentially inform individualized treatment?…”

Section: The Ph Patient Enginementioning

confidence: 99%

A perfectly imperfect engine: Utilizing the digital twin paradigm in pulmonary hypertension

Walker,

Moore,

Ataya

et al. 2024

Pulm. circ.

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Pulmonary hypertension (PH) is a severe medical condition with a number of treatment options, the majority of which are introduced without consideration of the underlying mechanisms driving it within an individual and thus a lack of tailored approach to treatment. The one exception is a patient presenting with apparent pulmonary arterial hypertension and shown to have vaso‐responsive disease, whose clinical course and prognosis is significantly improved by high dose calcium channel blockers. PH is however characterized by a relative abundance of available data from patient cohorts, ranging from molecular data characterizing gene and protein expression in different tissues to physiological data at the organ level and clinical information. Integrating available data with mechanistic information at the different scales into computational models suggests an approach to a more personalized treatment of the disease using model‐based optimization of interventions for individual patients. That is, constructing digital twins of the disease, customized to a patient, promises to be a key technology for personalized medicine, with the aim of optimizing use of existing treatments and developing novel interventions, such as new drugs. This article presents a perspective on this approach in the context of a review of existing computational models for different aspects of the disease, and it lays out a roadmap for a path to realizing it.

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Section: The Ph Patient Enginementioning

confidence: 99%

A perfectly imperfect engine: Utilizing the digital twin paradigm in pulmonary hypertension

Walker,

Moore,

Ataya

et al. 2024

Pulm. circ.

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“…However, mutations in genes responsible for familial forms of PAH like bone morphogenetic protein receptor 2 ( BMPR2 ), activin-like receptor kinase-1 ( ALK-1 ), endoglin ( ENG ), mothers against decapentaplegic 9 ( SMAD9 ) have been detected only in a minority of patients in PAH-CHD ( 17 ). Other mutations, including those identified more recently in other subsets of PH, like T-box transcription factor 4 ( TBX4 ) and SRY-box transcription factor 17 ( SOX17 ), may play a role in the pathophysiology of PAH-CHD and help explain individual susceptibility ( 18 - 20 ).…”

Section: Pah-chdmentioning

confidence: 99%

Pulmonary vascular disease as a complication of pediatric congenital heart diseases

Wacker¹,

Joye²,

Genecand³

et al. 2023

Transl Pediatr

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Congenital and acquired heart diseases can cause pulmonary hypertension (PH) in children, either by increasing pulmonary blood flow (PBF), left atrial pressure (LAp), and/or pulmonary vascular resistance (PVR). Pathophysiological process of pulmonary vascular disease (PVD) in different types of congenital heart diseases (CHDs) are reviewed hereafter. As with other types of PH, a rigorous diagnostic evaluation is mandatory to characterize the etiology of the PH, rule out other or additional causes of PH, and establish a risk profile. Cardiac catheterization remains the gold standard exam for PH diagnosis. Treatment of pulmonary arterial hypertension (PAH) associated with CHD (PAH-CHD) can then be started according to the recent guidelines recommendations, although most of the evidence is extrapolated from studies on other causes of PAH. PH in pediatric heart disease is often multifactorial, and sometimes unclassifiable, making the management of these patients complicated. The operability of patients with a prevalent left-to-right shunt and increase of PVR, the management of children with PH associated with left-sided heart disease, the challenges of pulmonary vascular disorders in children with univentricular heart physiology and the role of vasodilator therapy in failing Fontan patients are some of the hot topics discussed in this review.

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“…Patients with persistent pulmonary hypertension of the newborn (Group 1.6 [ 4 ]) often present with complex comorbidities or disorders and may harbour genetic variants in developmental genes [ 55 ]. The exact influence of the genes on the phenotype of the patients, apart from the acknowledged PAH genes such as TBX4 and BMPR2 , remains to be established [ 93 , 94 ].…”

Section: Areas Of Uncertaintymentioning

confidence: 99%

Genetic counselling and testing in pulmonary arterial hypertension: a consensus statement on behalf of the International Consortium for Genetic Studies in PAH

Eichstaedt

Belge²,

Chung³

et al. 2022

Eur Respir J

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Pulmonary arterial hypertension (PAH) is a rare disease, which can be caused by (likely) pathogenic germline genomic variants. In addition to the most prevalent disease gene, termedbone morphogenetic protein receptor 2(BMPR2), several genes, some belonging to distinct functional classes, are also now known to predispose to the development of PAH. As a consequence, specialist and non-specialist clinicians and health care professionals, are increasingly faced with a range of questions regarding the need for, approaches to and the benefits and risks, of genetic testing for PAH patients and/or related family members. We provide a consensus-based approach to recommendations for genetic counselling and assessment of current best practice for disease gene testing. We provide a framework and the type of information to be provided to patients and relatives, through the process of genetic counselling, and describe the presently known disease causal genes, to be analysed. Benefits of including molecular genetic testing within the management protocol of patients with PAH, include identification of individuals misclassified by other diagnostic approaches, the optimisation of phenotypic characterisation for aggregation of outcome data, including in clinical trials and importantly through cascade screening, the detection of healthy causal variant carriers, to whom regular assessment should be offered.

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Molecular genetics of pulmonary hypertension in children

Cited by 5 publications

References 67 publications

A perfectly imperfect engine: Utilizing the digital twin paradigm in pulmonary hypertension

A perfectly imperfect engine: Utilizing the digital twin paradigm in pulmonary hypertension

Pulmonary vascular disease as a complication of pediatric congenital heart diseases

Genetic counselling and testing in pulmonary arterial hypertension: a consensus statement on behalf of the International Consortium for Genetic Studies in PAH

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