Background Hypertrophic cardiomyopathy (HCM) is the most common inheritable cardiac disease and is characterised by unexplained ventricular myocardial hypertrophy. HCM is highly heterogeneous and is primarily caused by the mutation of genes encoding sarcomere proteins. As a result of its genetic basis, we investigated the underlying cause of HCM in a Chinese family by whole‐exome sequencing. Methods Whole‐exome sequencing was performed for seven clinically diagnosed HCM family members and the resulting single nucleotide variants associated with cardiac hypertrophy or heart development were analysed by a polymerase chain reaction and Sanger sequencing. Results A non‐frameshift deletion mutation (p.S527del) of Formin Homology 2 Domain Containing 3 (FHOD3) was detected in all of the affected family members and was absent in all unaffected members, with the exception of one young member. Moreover, three single nucleotide variants associated with heart development and morphogenesis were identified in the proband but were absent in the other affected subjects. Conclusions This is the first HCM family case of FHOD3 (p.S527del) variation in Asia. Additionally, RNF207 (p.Q268P), CCM2 (p. E233K) and SGCZ (p.Q134X) may be related to the clinical heterogeneity of the family. The present study could enable the provision of genetic counseling for this family and provide a basis for future genetic and functional studies.

Objectives Isolated prenatal ventricular disproportion with a dominant right ventricle represents a challenge in decision‐making for both physicians and pregnant women. In the current study, we sought to delineate the postnatal outcomes of these cases. Methods This retrospective analysis included consecutive cases of isolated ventricular disproportion identified using complete fetal echocardiography at the Fetal Heart Center of Xinhua Hospital from January 2014 to October 2017. Postnatal cardiac outcome was examined using transthoracic echocardiography within the first 6 months after birth. Results A total of 90 fetuses were included in the final analysis. The median gestational age (GA) at diagnosis was 29 weeks (range 24 to 36). At postnatal examination, cardiac malformations were detected in 39 cases (43.3%), including 25 (27.8%) cases of congenital cardiac septal defects, eight (8.9%) of persistent left superior vena cava, four (4.4%) of left‐sided obstructive diseases, and one (1.1%) case of coronary fistula. Nineteen cases (21.1%) with fetal cardiac malformations had significant lower GA at diagnosis (P = .01) and greater right to left ventricle ratio (1.38 vs 1.30, P = .02). Neonatal surgical intervention was not required in any of the cases. Conclusions Isolated prenatal ventricular disproportion with a dominant right ventricle comprises minor postnatal cardiac malformations and doesn't require neonatal intervention.

Methylmalonic acidaemia (MMA) has been reported to be associated with cardiovascular involvement, especially for the combined type with homocystinuria. We have screened 80 control subjects and 99 MMA patients (23 isolated type and 76 combined type) using electrocardiograph and echocardiography. 32 cases (34%) of ECG changes were found including sinus tachycardia (n = 11), prolonged QTc interval (n = 1), I-degree atrioventricular block (n = 1), left axis deviation (n = 5) and T wave change (n = 14). By echocardiography, 8 cases of congenital heart disease were found in 4 combined MMA patients (5.3%) including ventricular septal defect (n = 2), atrial septal defect (n = 3), patent ductus arteriosus (n = 1) and coronary artery-pulmonary artery fistula (n =2). Pulmonary hypertension (n = 2) and hypertrophic cardiomyopathy (n = 1) in combined subtype were also noted. Moreover, echocardiographic parameters were analyzed by multiple regression to clarify the influence of different subtypes on cardiac function. It was found that the left ventricular mass index (LVMI) was significantly reduced only in combined subtype [R = −3.0, 95%CI (−5.4, −0.5), P = 0.017]. For left ventricle, the mitral E' velocity was significantly reduced [isolated type: R = −1.8, 95%CI (−3.3, −0.4), P = 0.016; combined type: R = −2.5, 95%CI (−3.5, −1.5), P < 0.001], the global longitudinal strain (GLS) was the same [isolated type: R = −1.4, 95%CI (−2.3, −0.4), P = 0.007; Combined type: R = −1.1, 95%CI (−1.8, −0.4), P = 0.001], suggesting weakened left ventricular diastolic and systolic functions in both subtypes. For right ventricle, only in combined subtype, the tricuspid E' velocity was significantly reduced [R = −1.4, 95%CI (−2.6, −0.2), P = 0.021], and the tricuspid annular plane systolic excursion (TAPSE) was the same [R = −1.3, 95%CI (−2.3, −0.3), P=0.013], suggesting impaired right ventricular systolic and diastolic function. In conclusion, isolated and combined types showed different pattern of cardiac dysfunction, specifically the former only affected the left ventricle while the latter affected both ventricles. And it is necessary to perform echocardiographic screening and follow up in both MMA subtypes.