Familial Ebstein's anomaly, left ventricular noncompaction, and ventricular septal defect associated with an MYH7 mutation

Abstract

Aspergillus is a rare cause of endocarditis. [1][2][3] The prognosis for AE is poor, with only a third of reported patients surviving the acute episode, in part because of immunocompromise, delay in diagnosis, systemic dissemination, and multiple embolic episodes. 1 Only 5 cases of infective endocarditis caused by the species A terreus have been reported. 1 To the best of our knowledge, this is the first reported case of prosthetic valve endocarditis caused by A terreus.Early and accurate diagnosis is the most critical step in the treatment of AE and requires a high index of suspicion. The occurrence of peripheral emboli is the most common presenting feature and in a culture-negative infective endocarditis setting should raise the suspicion of AE. 1,3,4 Echocardiography reveals large vegetations on the valve(s), but blood cultures are almost always negative. [1][2][3] Ultimately, the diagnosis of Aspergillus requires histology and tissue culture confirmation from vegetations or emboli. Determining species is critical, because A terreus species is almost always resistant to amphotericin B, and voriconazole is the antifungal drug of choice, often in combination with an echinocandin. 1 Mortality is extremely high among those who receive antifungal therapy alone. [1][2][3] Successful treatment of AE requires combination of appropriate antifungal therapy and radical surgical debridement. Despite adequate combined antifungal and radical surgical treatment, recurrence after AE as high as 40% has been reported, adding to the dismal prognosis. [1][2][3] As a consequence, we now recommend antifungal suppression for life.

A Dutch MYH7 founder mutation, p.(Asn1918Lys), is associated with early onset cardiomyopathy and congenital heart defects

“…From a developmental point of view, the currently reported CHD (Ebstein’s anomaly, VSD, coarctation of the aorta and BAV) are all related to epicardial deficiencies [ 24 ] and, especially coarctation of the aorta, but also VSD and Ebstein’s anomaly, are known to be associated with BAV [ 25 ]. Although previous reports have described these CHDs in patients with specific MYH7 mutations [ 4 , 6 – 8 , 26 , 27 ] residing in the head and rod domain of the gene, p. (Asn1918Lys) is the only CHD-associated mutation that affects the tail region of the gene. Moreover, all previously described patients with an MYH7 mutation and a CHD also had cardiomyopathy.…”

A Wide and Specific Spectrum of Genetic Variants and Genotype–Phenotype Correlations Revealed by Next‐Generation Sequencing in Patients with Left Ventricular Noncompaction

“…This genetic spectrum is quite different from previous studies in patients with hypertrophic cardiomyopathy or dilated cardiomyopathy (Table ). In patients with hypertrophic cardiomyopathy, mutations in MYBPC3 and MYH7 are most commonly detected . In contrast, in patients with dilated cardiomyopathy, variants in titin are most commonly detected, whereas variants in MYH7 and MYBPC3 account for <1% .…”

Left ventricular noncompaction − Risk stratification and genetic consideration −

“…Most cases of Ebstein anomaly are sporadic and familial cases are rare, but various associated cardiovascular abnormalities have been reported, including LVNC or hyper trabeculation of the left ventricle and ventricular septal defect (VSD) [44,46]. Genetic screening revealed high incidence of MYH7 mutations in Ebstein anomaly, predominantly found in Ebstein anomaly associated with LVNC [47,48] (Fig. 6).…”