Systemic and ocular manifestations of a patient with mosaic ARID1A‐associated Coffin‐Siris syndrome and review of select mosaic conditions with ophthalmic manifestations

Abstract

Mosaic genetic mutations may be somatic, germline, or "gonosomal" and have the potential to cause genetic syndromes, disorders, or malformations. Mutations can occur at any point in embryonic development and the timing determines the extent of distribution of the mutation throughout the body and different tissue types. The eye and visual pathway offer a unique opportunity to study somatic and gonosomal mosaic mutations as the eye consists of tissues derived from all three germ layers allowing disease pathology to be assessed with noninvasive imaging. In this review, we describe systemic and ocular manifestations in a child with mosaic Coffin-Siris syndrome. The patient presented with a significant medical history of accommodative esotropia and hyperopia, macrocephaly, polydactyly, global developmental delay, hypotonia, ureteropelvic junction (UPJ) obstruction, and brain MRI abnormalities. The ophthalmic findings in this patient were nonspecific, however, they are consistent with ocular manifestations reported in other patients with Coffin-Siris syndrome. We also review ophthalmic findings of select mosaic chromosomal and single-gene disorders. Ophthalmic assessment alongside clinical genetic testing may play an important role in diagnosis of genetic syndromes as well as understanding disease pathology, particularly when mosaicism plays a role.

Introduction to the special issue on Ophthalmic Genetics: Vision in 2020

“…Finally, this section concludes with a series of papers highlighting the wide spectrum of disorders arising from the same genetic locus. These include novel clinical and molecular descriptions of adult forms of peroxisomal disorders (Heimler syndrome; Daich Varela et al, 2020), inborn errors of metabolism (Nonsyndromic retinal degeneration; Schiff et al, 2020), and the wide spectrum of ocular phenotypes arising from postzygotic genetic mosaicism (Coffin‐Siris syndrome; Miraldi Utz et al, 2020).…”