PHF21A Related Disorder: Description of a New Case

( ) gene, located in the short arm of chromosome 11, encodes for BHC80, a component of the Lysine Specific Demethylase 1, Corepressor of REST (LSD1-CoREST) complex. BHC80 is mainly expressed in the human fetal brain and skeletal muscle and acts as a modulator of several neuronal genes during embryogenesis. Data from literature relates variants with Potocki-Shaffer Syndrome (PSS), a contiguous gene deletion disorder caused by the haploinsufficiency of , , and genes. Clinical cardinal features of PSS syndrome are multiple exostoses (due to the involvement), biparietal foramina (due to the involvement), intellectual disability, and craniofacial anomalies (due to the involvement). To date, to the best of our knowledge, a detailed description of -related disorder clinical phenotype is not described in the literature; in fact, only 14 subjects with microdeletion frameshift or nonsense variants concerning only gene have been reported. All reported cases did not present or variants, and their clinical features did not fit with PSS diagnosis. Herein, by using Exome sequencing, and Sanger sequencing of the region of interest, we describe a case of a child with a paternally inherited (mosaicism of 5%) truncating variant of the gene (c.649_650del; p.Gln217ValfsTer6), and discuss the new evidence. In conclusion, these patients showed varied clinical expressions, mainly including the presence of intellectual disability, epilepsy, hypotonia, and dysmorphic features. Our study contributes to describing the genotype-phenotype spectrum of patients with PHF21A-related disorder; however, the limited data in the literature have been unable to provide a precise diagnostic protocol for patients with -related disorder.