Lethal acantholytic epidermolysis bullosa- a report on the prenatal phenotype of two cases and a review of antenatal sonographic signs of congenital denuding skin diseases.

Abstract

Background: The DSP gene encodes the desmosomal protein desmoplakin and is located on chromosome 6. Pathogenic variants in this gene have been linked to different phenotypes that may include the skin, hair, nails, teeth, and the heart. Lethal acantholytic epidermolysis bullosa (LAEB, OMIM # 609638) is a severe and lethal form of epidermolysis bullosa, caused by biallelic pathogenic variants in the DSP gene.

Case presentation: This report describes two fetuses from the same family, both affected by LAEB. The parents were second degree cousins. Both fetuses showed multiple sonographic abnormalities antenatally. The first fetus had a lemon shaped skull, an abnormal profile with frontal bossing, flat nasal bridge, nasal hypoplasia and micrognathia. There was increased pericardial fluid, situs ambiguous (left stomach with dextrocardia) and hypoplastic aortic arch. The kidneys were suspected as dysplastic and indeed there was also oligohydramnios. Echogenic sediment was noted in the fetal stomach. The fetus was small for gestational age (SGA) with an estimated fetal weight (EFW) under the 3rd percentile. The second fetus exhibited a novel sonographic sign - constantly open eyelids. Additional notable sonographic signs were echogenic amniotic fluid, and an abnormal profile comprising of flat nasal bridge, hypoplastic nose and micrognathia. Furthermore, hypospadias was suspected as well as abnormal scrotum. The scan revealed echogenic sediment in stomach and SGA fetus with EFW under 3rd percentile similarly to the previous pregnancy. After delivery severe extensive skin and mucosal erosion and sloughing were evident and the neonate succumbed at day 2 of life. Extensive genetic workup diagnosed LAEB in both children.

Discussion and conclusions: This is the first report to describe the antenatal sonographic phenotype of LAEB. We discuss the diverse phenotypes of DSP gene pathogenic variants and review the specific biochemical and sonographic findings in the context of congenital skin denudation diseases.