RAS/mitogen activated protein kinase (MAPK) pathway dysregulation, triggered by germline mutations in the involved genes, leads to a congenital syndrome termed “RASopathy.” Each form of RASopathy expresses a unique clinical phenotype; however, they share a series of functional and morphological organ abnormalities, including cardiac malformations, specific facial features, skeletal abnormalities, and intellectual disabilities. Secondary hypertrophic cardiomyopathy is the characteristic cardiac phenotype of RASopathy; its presence is strongly associated with heart failure-related mortality and sudden death. Therefore, RASopathy-associated hypertrophic cardiomyopathy (RAS-CMP) is a disease of priority in pediatric cardiology. However, the complete picture of its pathogenesis remains to be elucidated. Along with the development of novel molecular therapeutics, improving the quality of RASopathy care through collaborations between basic research and clinical practice is significantly needed. This review aimed to introduce the current evidence surrounding RAS-CMP and outline the knowledge gaps that should be addressed. Moreover, from the viewpoint of biological analogies between RAS/MAPK-related cancers and RASopathies, we deepen our discussion of recently emerging clues for exploring novel therapeutic approaches to RASopathy care.

Background: The purpose of this study was to look at the current state of the adult patients with tetralogy of Fallot, the most common cyanotic congenital heart disease, to encourage social independence and healthy lifestyles.

Methods: On 186 patients, a questionnaire survey (understanding and anxiety about their heart diseases, treatments, social independence, and lifestyles) was administered. These data were also compared between patients with and without physical disability certification (a certified group and a noncertified group). Clinical data were extracted from the medical records.

Results: After excluding the cases without meeting the inclusion criteria, 112 patients (41 males, mean age 28 years) were studied. Eighty-three percent of 93 patients after excluding 19 students, were employed (66％ full-time employee) , half of them lived with their parents, and 71％ were concerned about their heart diseases. In terms of lifestyle, 28％ were dissatisfied with the quality of their sleep. The noncertified group (n=59) was assigned more professional tasks, whereas the certified group (n=53) was assigned more office duties. The certified group had more regular outpatient clinic visits and dental consultations, but also had a greater experience to drink alcohol and take a sleeping pill.

Conclusion: The study patients had a relatively good job rate and a high level of social independence, despite having a variety of anxiety disorders. It was suggested that some supports for anxiety and sleep disorder issues be implemented especially in the certified group.

A male neonate with transposition of the great arteries, ventricular septal defect, coarctation of the aorta, and a moderately hypoplastic right ventricle was transferred to our hospital. Following initial bilateral pulmonary artery banding, the arterial switch operation with ventricular septal defect closure and coarctation repair was performed, while atrial septal defect was left open. Two years after the operation, the diameter of the tricuspid valve annulus was found to be 10.8 mm (Z-score: −2.73), and bidirectional flow through atrial septal defect was observed on echocardiography. The patient underwent one and a half ventricular repair at 3 years of age. Thirteen years after the third operation, the patient is in a good general condition with normal sinus rhythm. At the latest investigation on echocardiography, no sign of right heart failure is observed; no dilatation of the inferior vena cava, no reversal flow in the inferior vena cava, and no right ventricular systolic dysfunction. The tricuspid valve diameter is 25.3 mm with balanced left and right ventricular cavities.

Moderate or severe tricuspid regurgitation is a poor prognostic factor for hypoplastic left heart syndrome (HLHS) and may require tricuspid valve repair at the time of the Norwood procedure. If complicated with tricuspid valve stenosis, a technique that does not worsen the stenosis must be selected. We present such a case; a male infant prenatally diagnosed with HLHS and underwent surgical repair of the valve on the 20th day of life. We performed a bridging technique across the tricuspid valve for repair of tricuspid regurgitation and stenosis associated with HLHS at the time of the Norwood procedure and successfully controlled regurgitation without worsening stenosis. This technique does not restrict the tricuspid valve inflow and is suitable for cases of combined tricuspid regurgitation and stenosis.

A 25-year-old woman with congenital aortic stenosis and severe intellectual disability associated with ring chromosome 18 syndrome was referred for surgical evaluation. She had previously undergone aortic valvuloplasty twice. Her aortic stenosis and regurgitation were severe, therefore another surgical intervention was planned. Preoperative contrast-enhanced computed tomography showed a narrow aortic annulus (19.0 mm diameter). Because anticoagulation after surgery was not considered feasible, bioprosthetic aortic valve replacement was performed in conjunction with the Konno procedure to enlarge the annulus. Her postoperative course was uneventful. Contrast-enhanced computed tomography after surgery showed the sinus of Valsalva properly enlarged, and distances between the coronary ostia and the leaflets of the bioprosthetic valve were sufficiently large, which may lower the risk of coronary flow obstruction when the aortic valve would be replaced further in a transcatheter valve-in-valve way. Bioprosthetic aortic valve replacement in anticipation of future use of such a transcatheter technique is a surgical option that should be considered for young adult patients with severe AS and difficulty in anticoagulation.