Broadening the ocular phenotypic spectrum of ultra-rare BRPF1 variants: report of two cases

ABSTRACT

Introduction

BRPF1 gene on 3p26-p25 encodes a protein involved in epigenetic regulation, through interaction with histone H3 lysine acetyltransferases KAT6A and KAT6B of the MYST family. Heterozygous pathogenic variants in BRPF1 gene are associated with Intellectual Developmental Disorder with Dysmorphic Facies and Ptosis (IDDDFP), characterized by global developmental delay, intellectual disability, language delay, and dysmorphic facial features. The reported ocular involvement includes strabismus, amblyopia, and refraction errors. This report describes a novel ocular finding in patients affected by variants in the BRPF1 gene.

Methods

We performed exome sequencing and deep ocular phenotyping in two unrelated patients (P1, P2) with mild intellectual disability, ptosis, and typical facies.

Results

Interestingly, P1 had a Chiari Malformation type I and a subclinical optic neuropathy, which could not be explained by variations in other genes. Having detected a peculiar ocular phenotype in P1, we suggested optical coherence tomography (OCT) for P2; such an exam also detected bilateral subclinical optic neuropathy in this case.

Discussion

To date, only a few patients with BRPF1 variants have been described, and none were reported to have optic neuropathy. Since subclinical optic nerve alterations can go easily undetected, our experience highlights the importance of a more detailed ophthalmologic evaluation in patients with BRPF1 variant.

KEYWORDS:

• BRPF1
• phenotyping
• optic nerve anomaly

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Consent for publication

Written informed consent was obtained from the parents for the publication of this case report.

Additional information

Funding

This study was supported in part by funds from the “Current Research Annual Funding” of the Italian Ministry of Health.