Gonadal Mosaicism as a Rare Inheritance Pattern in Recessive Genodermatoses: Report of Two Cases with Pseudoxanthoma Elasticum and Literature Review

TL;DR

This paper reports two cases of pseudoxanthoma elasticum caused by germline mosaicism and reviews literature on this rare inheritance pattern in skin disorders.

Contribution

The study presents two new cases of germline mosaicism in pseudoxanthoma elasticum and reviews existing literature on the topic.

Findings

Two families with pseudoxanthoma elasticum showed paternal germline mosaicism for an ABCC6 deletion.

A literature review identified 16 additional cases of gonadal mosaicism in autosomal recessive genodermatoses.

Segregation analysis data is often missing, suggesting potential underrepresentation of germline mosaicism.

Abstract

Germline mosaicism in autosomal recessive disorders is considered a rare disease mechanism with important consequences for diagnosis and patient counseling. In this report, we present two families with PXE in which paternal germline mosaicism for an ABCC6 whole-gene deletion was observed. The first family further illustrates the clinical challenges in PXE, with a typical PXE retinopathy in an apparently heterozygous carrier parent. A systematic review of the literature on gonadal mosaicism in autosomal recessive genodermatoses revealed 16 additional patients. As in most reported families, segregation analysis data are not mentioned, and this may still be an underrepresentation. Though rare, the possibility of germline mosaicism emphasizes the need for variant verification in parents and sibs of a newly diagnosed proband, as it has significant implications for genetic counseling and management.

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