Intellectual developmental disorder with dysmorphic facies and ptosis caused by copy number variation including the BRPF1 gene in Peruvian patient

Abstract

Background Intellectual developmental disorder with dysmorphic facies and ptosis (MIM #617333) is a very rare condition, characterized by more than 80% by language delay, intellectual disability, gross motor development delay, broad nasal bridge, hypertelorism, and hypotonia. This condition exhibits as autosomal dominant inheritance and is caused by a heterozygous variant in the BRPF1 gene. Additionally, the copy number variation in the terminal region of chromosome 3p (MIM #613792) has been shown to manifest in most patients as intellectual disability, motor delay, and hypotonia. Case presentation We present an 18-year-old male patient with facial dysmorphism, intellectual disability, ptosis, and congenital heart disease. Using chromosomal microarray analysis, a previously unreported 90 kb deletion involving seven genes was found. Conclusion When comparing our findings with 39 previous reports, we found that the common clinical features of this syndrome, such as gross motor delay, hypotonia, and congenital spinal cord abnormalities, were not observed in this patient. From the seven genes implicated in the deletion, only BRPF1 could be strongly correlated with the phenotype, according to its function and haploinsufficiency coefficients.

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

“…Additionally, some patients exhibit skeletal deformities (72%, 31/43), including hand (brachydactyly and brachymetacarpia) and foot (clubfoot or syndactyly) differences. However, a minority of patients with IDDDFP experience seizures (21%, 9/43) and structural brain abnormalities (50%, 10/20), often characterized by abnormal white matter signals under MRI and corpus callosum thinning [3,[5][6][7][8][9][10][11][12][13]. The affected family members in our report exhibited typical facial dysmorphisms of IDDDFP.…”

“…Fewer than 50 cases of IDDDFP have been reported, highlighting the scarcity of essential research data regarding the correlation between disease phenotypes and genotypes [3,[5][6][7][8][9][10][11][12][13]. In this study, we present a case involving a Chinese family exhibiting typical IDDDFP features, with the proband also presenting with infantile epilepsy and developmental delay.…”

Mosaicism in BRPF1-Related Neurodevelopmental Disorder: Report of Two Sisters and Literature Review

“…Common clinical features of IDDDFP include intellectual disability (ID), global developmental delay, hypotonia, facial dysmorphisms, ptosis, and/or blepharophimosis. Less frequently reported clinical features include hand and foot anomalies, brain anomalies, microcephaly, behavioral anomalies, growth retardation, and seizures [1][2][3][4][5][6][7][8][9]. Maternal mosaicism has been previously reported in Yan et al [2].…”

“…Those without reported phenotypic information were not included in our analysis [ 24 – 26 ]. Three patients from Mattioli et al [ 1 ] and one patient from Abarca-Barriga et al [ 5 ] were also excluded as they have larger multigene deletions.…”

Anemia and thrombocytopenia due to a novel BRPF1 variant in a family from Çanakkale with intellectual disability and dysmorphic facies: Case report and review of the literature

“…So far, the cardiac anomaly has not been widely reported (6/31). Small patent ductus arteriosus, atrial septal defect (Abarca‐Barriga et al, 2022; Yan et al, 2017), and sinus AV nodal pauses and blocks (Yan et al, 2020) were reported up to this point. Additionally, our patients demonstrated patent ductus arteriosus and large ventricular septal defect.…”