Genetic analysis of BRPF1 exon deletion variant causing intellectual developmental disorder with dysmorphic facies and ptosis in a Chinese family

Intellectual developmental disorders with dysmorphic facies and ptosis (IDDDFP) are rare neurological conditions caused by variants in the BRPF1 gene. They primarily manifest as intellectual disabilities (ID) alongside distinctive facial features, particularly ptosis and blepharophimosis. This study aimed to investigate the molecular etiology and phenotype of the inaugural IDDDFP family documented in China. Clinical data were collected and validated through trio-based whole-exome sequencing of DNA from the proband and her parents, complemented by quantitative polymerase chain reaction (qPCR). The proband, a 10-month-old girl, presented with focal seizures and developmental delays. Notably, she exhibited facial features similar to those of her mother and sister, including ptosis and blepharophimosis. Both the proband’s mother and sister also had mild ID. Genetic testing identified BRPF1 deletion variants in all affected individuals, resulting in exon 2–14 heterozygous deletion. The qPCR verification confirmed the wild-type BRPF1 in the proband’s father and eldest sister. A review of 46 documented patients with BRPF1 deficiency revealed that the primary clinical manifestations encompassed varying degrees of ID alongside special facial features, skeletal deformities, and ocular abnormalities. However, epilepsy was found to be rare in this syndrome. The syndrome has variable phenotypic features of neurodevelopmental disorders. Meanwhile, there seems to be a lack of correlation between phenotype and genotype. Our findings broaden the genotypic and phenotypic spectrum of individuals with genetically pathogenic variants of BRPF1. Moreover, they underscore the significance of recognizing ptosis and blepharophimosis associated with ID or seizures as potential signs of BRPF1 variants.