A Novel PACS1 Variant Associated With Schuurs-Hoeijmakers Syndrome Phenotype in an Indigenous Descendant in Brazil: A Case Report

Abstract

Schuurs-Hoeijmakers syndrome, an autosomal dominant disorder associated with mutations in the PACS1 gene, was initially identified in two unrelated children of European descent from a cohort of individuals with intellectual disabilities. This gene alteration significantly reduced cranial cartilaginous structures, inducing craniofacial alterations predominantly in a dominant-negative fashion. In this paper, we report a novel variant of PACS1 associated with Schuurs-Hoeijmakers syndrome: a boy aged two years and nine months of indigenous descent presenting with motor stereotypies, atypical sensory searches, language delay, and low socio-interactional reciprocity. Whole exome sequencing confirmed the presence of a heterozygous missense mutation c.943C>T p. (Arg315Trp) in the PACS1 gene. The phenotypic profile identified was similar to the other cases of Schuurs-Hoeijmakers syndrome described in the literature. This report highlights the importance of considering the possibility of PACS1 gene alterations and a diagnosis of Schuurs-Hoeijmakers syndrome in patients presenting craniofacial alterations associated with autistic features, psychomotor and language development delay.

Keywords: autism spectrum disorder (asd); intellectual disability (id); neurodevelopmental delay; pacs1; schuur-hoeijmakers’ syndrome.