Clinical Variability of Shashi-Pena Syndrome: A Novel ASXL2 Variant Associated with Overgrowth and Minor Neurodevelopmental Features.

Abstract

Introduction: Shashi-Pena syndrome (SHAPNS) is a rare congenital disorder characterized by macrocephaly, delayed psychomotor development with intellectual disability, hypotonia, seizures, episodic hypoglycemia, distinct facial features, and glabellar nevus flammeus, caused by heterozygous variants of the ASXL2 gene.

Case presentation: We report on a 15-year-old patient in care at our hospital since the age of 4 years presenting with minor neurodevelopmental problems, marked postnatal overgrowth without advanced bone age, and dental anomalies.

Conclusion: Patients described in the literature with SHAPNS are reported indicating a broad spectrum of clinical manifestations. The present patient manifests an atypical presentation of SHAPNS due to a novel heterozygous ASXL2 variant. This study supports the inclusion of SHAPNS in overgrowth disorders with macrocephaly, suggesting the analysis of the ASXL2 gene even in suspected subjects with normal bone age and confirms dental anomalies as a clinical feature of this syndrome. SHAPNS could be inferred even in the absence of developmental delay or epilepsy.