A Case of Gillespie Syndrome With Atypical Presentation

Abstract

Gillespie syndrome, a genetically inherited condition, is described as a disease that primarily affects the ocular and associated nervous systems. It is characterized by a clinical triad of bilateral aniridia, intellectual disability, and cerebellar ataxia, and is inherited in an autosomal dominant or recessive fashion. The most well-studied mutations related to this syndrome affect the inositol 1,4,5-trisphosphate receptor type 1 gene (ITPR1). Gillespie syndrome is an exceptionally uncommon diagnosis with less than 50 patients ever being diagnosed. We present a case of a patient with bilateral aniridia and ataxia but lacking intellectual disability, and moreover had no known family history of this syndrome. Our case report shows that Gillespie syndrome may not necessarily present with the classic "triad" of symptoms as previously described in the literature.

A bird’s eye view on the use of whole exome sequencing in rare congenital ophthalmic diseases

“…Besides PAX6 , the second most altered gene in our cohort turned out to be ITPR1 , whose either homozygous or heterozygous, dominant-negative, pathogenic variants are associated to the Gillespie syndrome—characterized by a triad of partial aniridia, non-progressive cerebellar ataxia, and intellectual disability [ 42 ]. Gillespie syndrome is an exceptionally uncommon diagnosis with <50 patients ever being diagnosed [ 43 ]. None of our patients (A210, A253, and A258) presented the classical triad of symptoms, with two out of three patients affected by intellectual disability.…”

“…No signs of ataxia were detected. This is not surprising given that papers describing patients with atypical presentations have been only recently published [ 43 ]. Furthermore, two MAB21L1 variants were found in our cohort, the hotspot mutation p.Arg51Leu and the previously published p.Phe52Cys (A180 and A97, respectively) [ 22 ].…”