Cutaneous squamous cell carcinoma in an autosomal-recessive Adams-Oliver syndrome patient with a novel frameshift pathogenic variant in the EOGT gene

Abstract

Aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD) are the characteristic findings of Adams-Oliver syndrome (AOS). The variable clinical spectrum further includes cardiac, neurologic, renal, and ophthalmological findings. Associated genes in AOS are in the Notch and the CDC42/Rac1 signaling pathways. Both autosomal-dominant and autosomal-recessive inheritances have been reported, the latter with pathogenic variants in DOCK6 or EOGT. The EOGT-associated recessive type of AOS has been postulated to present a more favorable prognosis. We here report a 12-year-old girl from a refugee family of Iraq with consanguineous parents. She was born with a severe phenotype of AOS presenting a large ACC of the scalp with an underlying skull defect, which was often infected and inflamed. Afterward, additional ulceration developed. Furthermore, the girl showed microcephaly, TTLD on both hands and feet, and neurological findings: spastic paresis, epilepsy and suspicion of intellectual deficit. Molecular genetic analysis (next-generation sequencing) revealed a novel frameshift mutation in the EOGT gene in Exon 13 in homozygous constellation: c.1013dupA p.(Asn338Lysfs*24). A biopsy within an ulceration at the scalp ACC showed a cutaneous squamous cell carcinoma (cSCC) with local invasive growth into the dura, the meninges, and the cortex. Treatment including surgical resection and focal irradiation was not curative and the girl deceased 6 months after initial diagnosis. This report on a patient with AOS and an autosomal-recessive EOGT gene variant dying of a local aggressive cSCC at an ACC lesion shows that close monitoring of ACC is essential.

Keywords: Adams-Oliver syndrome; EOGT gene; squamous cell carcinoma.