A Severe Form of Familial Desminopathy Due to a Homozygous Nonsense DES Variant in Two Siblings

Abstract

Familial primary desminopathies are usually autosomal dominantly inherited and present at the age of 20 to 40 years with progressive muscle weakness and atrophy, cardiomyopathy, and cardiac arrhythmias. Cardiac features may precede the muscular weakness. Here, we report the rare case of two siblings presenting with a desminopathy at pediatric age, due to homozygous nonsense variations (c.700G > T [p.Glu234Ter]) in DES, representing an autosomal recessive inheritance pattern. The homozygous state of these variants is expected to result in the complete absence of desmin production. Rare autosomal recessive DES variants are associated with an earlier clinical presentation (from childhood to early adulthood) and faster evolution compared with more common autosomal dominant variants. A normal resting electrocardiography (ECG) and cardiac ultrasound can be a pitfall, as seen in our patient who has extensive fibrotic scarring on cardiac magnetic resonance imaging (MRI). We recommend yearly cardiac ultrasound, yearly 24-hour Holter monitoring and 2 yearly cardiac MRI from the age of 10 years in all asymptomatic patients. Heterozygous patients usually have no or only mild complaints but, though not yet reported in autosomal recessive desminopathies, muscular complaints are possible, as seen in the father of our patients. The prognosis for these patients with desminopathy presenting in childhood is unpredictable but anticipated as poor.

Keywords

child - homozygous - recessive - desminopathy - cardiac - MRI

Author Contributions

L.C. conducted the research literature and wrote the draft version of this article. K.V.S. reviewed the genetic elements described in this paper. D.B. is the pediatric neurologist of these patients and reviewed the article. W.D. is the pediatric cardiologist of these patients and reviewed the article. L.C. prepared the final version of this article. All authors have improved and read the final version of this article.

Publication History

Received: 24 March 2022

Accepted: 02 June 2022

Accepted Manuscript online:
08 June 2022

Article published online:
28 August 2022

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