Aortic root dilatation and dilated cardiomyopathy in an adult with Tatton-Brown-Rahman syndrome

Abstract

Tatton-Brown-Rahman syndrome is an autosomal dominant overgrowth syndrome caused by pathogenic DNMT3A variants in the germline. Clinical findings of tall stature due to postnatal overgrowth, intellectual disability, and characteristic facial features, are the most consistent findings observed in patients with Tatton-Brown-Rahman syndrome (TBRS). Since the syndrome was first described in 2014, an expanding spectrum of neuropsychiatric, musculoskeletal, neurological, and cardiovascular manifestations have been reported. However, most TBRS cases described in the literature are children with de novo DNMT3A variants, signaling a need to better characterize the phenotypes in adults. In this report, we describe a 34 year old referred to genetics for possible Marfan syndrome with aortic root dilatation, mitral valve prolapse, and dilated cardiomyopathy, who was diagnosed with TBRS due to a heterozygous de novo DNMT3A variant. This represents the third reported TBRS case with aortic root dilation and the second with cardiomyopathy. Collectively, these data provide evidence for an association with aortic disease and cardiomyopathy, highlight the clinical overlap with Marfan syndrome, and suggest that cardiovascular surveillance into adulthood is indicated.

Keywords: DNMT3A; Tatton-Brown-Rahman syndrome; aortic aneurysm; cardiomyopathy; overgrowth syndrome.

Figure 1

Transthoracic echocardiogram and cardiac MRI. (a) Dilated aortic root and left ventricle via parasternal long axis view. (b) Cardiac MRI demonstrating a dilated aortic root and left ventricle with normal ascending aortic dimensions distally.

Figure 2

Phenotypic features. (a) Long slender fingers; more impressive on the left. (b) Long toes with mild flexion contractures; more prominent on the left.