Search

CTNNB1 [OMIM *116806] encodes β‐catenin, an integral part of the cadherin/catenin complex, which functions as effector of Wnt signaling. CTNNB1 is highly expressed in brain as well as in other tissues, including heart. Heterozygous CTNNB1 pathogenic variations are associated with a neurodevelopmental disorder characterized by spastic diplegia and visual defects (NEDSDV) [OMIM #615075], featuring psychomotor delay, intellectual disability, behavioral disturbances, movement disorders, visual defects and subtle facial and somatic features. We report on a new series of 19 NEDSDV patients (mean age 10.3 years), nine of whom bearing novel CTNNB1 variants. Notably, five patients showed congenital heart anomalies including absent pulmonary valve with intact ventricular septum, atrioventricular canal with hypoplastic aortic arch, tetralogy of Fallot, and mitral valve prolapse. We focused on the cardiac phenotype characterizing such cases and reviewed the congenital heart defects in previously reported NEDSDV patients. While congenital heart defects had occasionally been reported so far, the present findings configure a higher rate of cardiac anomalies, suggesting dedicated heart examination to NEDSDV clinical management. [ABSTRACT FROM AUTHOR]

Congenital heart disease (CHD) and hypertrophic cardiomyopathy (HCM) are common features in patients affected by RASopathies. The aim of this study was to assess genotype‐ phenotype correlations, focusing on the cardiac features and outcomes of interventions for cardiac conditions, in a single‐center cohort of 116 patients with molecularly confirmed diagnosis of RASopathy, and compare these findings with previously published data. All enrolled patients underwent a comprehensive echocardiographic examination. Relevant information was also retrospectively collected through the analysis of clinical records. As expected, significant associations were found between PTPN11 mutations and pulmonary stenosis (both valvular and supravalvular) and pulmonary valve dysplasia, and between SOS1 mutations and valvular defects. Similarly, HRAS mutations were significantly associated with HCM. Potential associations between less prevalent mutations and cardiac defects were also observed, including RIT1 mutations and HCM, SOS2 mutations and septal defects, and SHOC2 mutations and septal and valve abnormalities. Patients with PTPN11 mutations were the most likely to require both a primary treatment (transcatheter or surgical) and surgical reintervention. Other cardiac anomalies less reported until recently in this population, such as isolated functional and structural mitral valve diseases, as well as a sigmoid‐shaped interventricular septum in the absence of HCM, were also reported. In conclusion, our study confirms previous data but also provides new insights on cardiac involvement in RASopathies. Further research concerning genotype/phenotype associations in RASopathies could lead to a more rational approach to surgery and the consideration of drug therapy in patients at higher risk due to age, severity, anatomy, and comorbidities. [ABSTRACT FROM AUTHOR]

Smith Magenis syndrome (SMS) is a rare neurobehavioral disorder caused by 17p11.2 microdeletion encompassing Retinoic Acid‐Induced 1 (RAI1) gene (90% of cases) or by RAI1 point mutation (10% of cases). The neuropsychological phenotype of individuals with 17p11.2 deletion and in those with RAI1 variants mostly overlaps. However, cardiac defects have been described only in patients with a deletion so far. Here, we present the first case of a patient affected by SMS caused by RAI1 variant in whom a severe congenital pulmonary valve stenosis was diagnosed at birth, requiring trans catheter dilatation in the first month of life. This case expands the phenotypic spectrum associated with RAI1 variants in SMS, describing a previously unreported association with a congenital heart disease. [ABSTRACT FROM AUTHOR]