The Phenotypic and Genotypic Spectrum of BRPF1-Related Disorder: 29 New Patients and Literature Review.

Abstract

Intellectual Developmental Disorder with Dysmorphic Facies and Ptosis (IDDDFP) is a rare autosomal dominant syndrome caused by pathogenic variants in the BRPF1 gene, which is critical for chromatin regulation. This study expands the clinical and molecular spectrum of IDDDFP by analysing 29 new patients from 20 families with confirmed BRPF1 variants. Our cohort presented with a wide range of clinical features including developmental delay, intellectual disability (ID) and characteristic dysmorphic facial features such as ptosis, blepharophimosis and a broad nasal bridge. New phenotypic features identified include palpebral oedema, laterally elongated eyebrows, low hanging columella and hypertrichosis. Neuropsychological assessment reveals a predominance of mild to moderate ID, with cognitive profiles showing variability in verbal and visual processing. Structural abnormalities such as agenesis of the corpus callosum and ocular defects were noted, consistent with previous studies but with some differences. Familial analysis revealed variability in clinical expression. Our findings highlight the diverse clinical manifestations of BRPF1-related disorders and suggest that comprehensive ophthalmological evaluation is essential for the management of these patients.