TBL1XR1 associated intellectual disability, a new missense variant with dysmorphic features plus autism: Expanding the phenotypic spectrum

Missense and frameshift pathogenic variants and microdeletions involving TBL1XR1 gene have been described in patients with intellectual disability, autism, Rett-like features and schizophrenia, some of them with the clinical diagnosis of Pierpont syndrome, a rare pattern of multiple congenital anomalies, but others without dysmorphic findings or with non-specific ones, and also patients with only some of the features associated with Pierpont syndrome. We here present a case with a de novo novel missense variant in TBL1XR1 gene with overlapping features with Pierpont syndrome and autism, a neurobehavioral manifestation not previously reported in Pierpont syndrome. This patient expands the phenotypic spectrum of TBL1XR1 gene pathogenic variants.

Automated summary

Missense and frameshift pathogenic variants, as well as microdeletions involving the TBL1XR1 gene, have been linked to intellectual disability, autism, Rett-like features, and schizophrenia in patients. This case report describes a novel missense variant in the TBL1XR1 gene associated with overlapping features of Pierpont syndrome and autism, expanding the phenotypic spectrum of pathogenic variants in this gene.