Abstract
Primary cardiomyopathy is one of the most common inherited cardiac diseases and harbors significant phenotypic and genetic heterogeneity. Because of this, genetic testing has become standard in treatment of this disease group. Indeed, in recent years, next-generation DNA sequencing has found broad applications in medicine, both as a routine diagnostic tool for genetic disorders and as a high-throughput discovery tool for identifying novel disease-causing genes. We describe a male infant with primary dilated cardiomyopathy who was diagnosed using intrauterine echocardiography and found to progress to hypertrophic cardiomyopathy after birth. This proband was born to a nonconsanguineous family with a past history of a male fetus that died because of cardiac abnormalities at 30 wk of gestation. Using whole-exome sequencing, a novel homozygous frameshift mutation (c.2018delC; p.Gln675SerfsX30) in ALPK3 was identified and confirmed with Sanger sequencing. Heterozygous family members were normal with echocardiographic examination. To date, only two studies have reported homozygous pathogenic variants of ALPK3, with a total of seven affected individuals with cardiomyopathy from four unrelated consanguineous families. We include a discussion of the patient's phenotypic features and a review of relevant literature findings.
Highlights
We report a null variant in the autosomal recessively inherited cardiomyopathy gene ALPK3, which was identified in a patient who initially presented with dilated cardiomyopathy (DCM) that later progressed to hypertrophic cardiomyopathy (HCM)
When he was 4 mo old, his weight was 5010 g (10th percentile), height was 59 cm (25–50th percentile), and head circumference was 39 cm (10th percentile). His examination revealed dysmorphic face including low-set ears and high arched palate
This study underscores the essential role of genetic testing in congenital cardiomyopathy, which should guide appropriate counseling and screening of other family members
Summary
Ontology terms: hypertrophic cardiomyopathyCardiomyopathy (CMP) is classified into primary and secondary forms based on the involvement of other organ systems (Maron et al 2006). Idiopathic DCM carries a prevalence likely exceeding 1 in 250 (Hershberger et al 2013) and is histologically characterized by cardiomyocyte hypertrophy, loss of myofibrils, and interstitial fibrosis (Cahill et al 2013). Both HCM and DCM are responsible for heart failure, arrhythmias, and sudden cardiac death at any age worldwide (Maron and Maron 2013); and DCM is the most common indication for cardiac transplantation (Stehlik et al 2012). Other inheritance patterns have been reported, including X-linked (Towbin et al 1993), mitochondrial (Zaragoza et al 2011), and autosomal recessive transmission in DCM and X-linked and recessive in HCM (Burke et al 2016)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call