CSNK2B Mutation: A Rare Cause of IGHD

Area of Science:

• Genetics
• Endocrinology
• Neurodevelopmental Disorders

Background:

• Poirier-Bienvenu neurodevelopmental syndrome (POBINDS) is a rare genetic disorder linked to CSNK2B variants, typically causing severe epilepsy and developmental delays.
• Some patients present with mild intellectual disability (ID) and short stature, often due to growth hormone deficiency (GHD).

Purpose of the Study:

• To investigate a case of POBINDS presenting primarily as isolated growth hormone deficiency (IGHD).
• To assess the frequency of CSNK2B variants in patients with GHD and ID or epilepsy.

Main Methods:

• Whole genome sequencing (WGS) was performed on a patient with IGHD.
• NGS panel analysis of CSNK2B was conducted on 44 patients with GHD and ID/epilepsy, and a cohort of 68 GHD patients.

Main Results:

• A de novo pathogenic variant in CSNK2B was identified in a patient with IGHD, mild ID, and a history of febrile convulsions, consistent with POBINDS.
• No CSNK2B pathogenic variants were found in the screened patient cohorts.

Conclusions:

• POBINDS should be considered in the differential diagnosis of IGHD, particularly when accompanied by mild ID.
• Pediatricians should be aware of the varied clinical presentations of POBINDS, including IGHD as a primary symptom.