2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Novel Variant in <em>DSP</em> Associated with Lethal Acantholytic Epidermolysis Bullosa and Bradyarrhythmia

Pdf Summary

This document discusses a case presentation of a newborn with a rare condition called lethal acantholytic epidermolysis bullosa (LAEB) and third-degree heart block. The prenatal history reveals fetal growth restriction and abnormally small long bones. The neonate is born via cesarean section and exhibits extensive skin peeling and exposed dermis. Dysmorphology exam findings include low set ears, superficial palmar clefts, triangular thumbs, and syndactyly of the toes. Dermatologic findings show epidermal separation, subepidermal separation, and acantholysis with areas of necrosis. Cardiac findings include a patent ductus arteriosus, patent foramen ovale, and right ventricular dilation. On the 17th day of life, the newborn develops bradycardia and hypotension. The cytogenetic and molecular diagnosis reveals a pathogenic variant in the DSP gene, which codes for the protein desmoplakin. This case expands our understanding of the variants in DSP and the associated prenatal and postnatal phenotypes. The baby unfortunately experiences cardiopulmonary failure and dies on the 20th day of life. The case also suggests the presence of a founder variant in a population not previously sequenced, as indicated by the biparental inheritance of the same variant without known consanguinity. Various references are cited to support the discussion, including studies on twins with LAEB caused by DSP mutations, a case of LAEB with arrhythmogenic cardiomyopathy, and research on patients with genetic variation in desmoplakin and arrhythmogenic right ventricular cardiomyopathy.

Asset Subtitle

Presenting Author - Asha N. Talati, MD, MS; Co-Author - Joseph Cornett, MD; Co-Author - Brianna Frame, MD; Co-Author - Emily E. Hardisty, MS, CGC; Co-Author - Sarah White, MD; Co-Author - Neeta L. Vora, MD, FACMG; Co-Author - Elizabeth R. Jalazo, MD;

Meta Tag

Bone/Joint Abnormalities

Cardiovascular System

Congenital Anomaly

Dysmorphology

Fetal Pathology

Genome sequencing

Genotype-Phenotype Correlations

Malformation

Phenotype

Co-Author Joseph Cornett, MD

Co-Author Brianna Frame, MD

Co-Author Emily E. Hardisty, MS, CGC

Co-Author Sarah White, MD

Co-Author Neeta L. Vora, MD, FACMG

Co-Author Elizabeth R. Jalazo, MD

Presenting Author Asha N. Talati, MD, MS

Keywords

lethal acantholytic epidermolysis bullosa

third-degree heart block

fetal growth restriction

small long bones

cesarean section

skin peeling

exposed dermis

low set ears

superficial palmar clefts