Pituitary stalk interruption syndrome due to novel ROBO1 mutation presenting as combined pituitary hormone deficiency and central diabetes insipidus

Raiz Ahmad Misgar; Ankit Chhabra; Ajaz Qadir; Sidharth Arora; Arshad Iqbal Wani; Mir Iftikhar Bashir; Shariq Rashid Masoodi

doi:10.1515/jpem-2023-0541

Article

Pituitary stalk interruption syndrome due to novel ROBO1 mutation presenting as combined pituitary hormone deficiency and central diabetes insipidus

Raiz Ahmad Misgar , Ankit Chhabra , Ajaz Qadir , Sidharth Arora , Arshad Iqbal Wani , Mir Iftikhar Bashir and Shariq Rashid Masoodi

Published/Copyright: March 7, 2024

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 37 Issue 5

Abstract

Objectives

The genetic causes of pituitary stalk interruption syndrome (PSIS) remain elusive in 95 % of cases. The roundabout receptor-1 gene (ROBO1) plays critical roles in axonal guidance and cell migration. Recently, mutations in the ROBO1 gene have been reported patients with PSIS.

Case presentation

We report a 2.9-year-old boy with PSIS who presented with combined pituitary hormone deficiency, central diabetes insipidus, and the classical triad of MRI findings. Through clinical exome sequencing using next-generation sequencing techniques, a previously unidentified novel heterozygous frame shift mutation in the ROBO1 gene was identified. This is the first report of ROBO1 mutation associated with posterior pituitary dysfunction.

Conclusions

We conclude and emphasize that ROBO1 should be investigated in patients with PSIS. Our case is unique in the published literature in that we are first time reporting posterior pituitary dysfunction as manifestation of ROBO1 mutation. The full clinical spectrum of the mutations may not be fully known.

Keywords: combined pituitary hormone deficiency; central diabetes insipidus; pituitary stalk interruption syndrome; roundabout receptor-1 gene

Corresponding author: Dr. Raiz Ahmad Misgar, DM, Additional Professor, Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India, Phone: 91 09419090026, Fax: +91 19 4240 3470, E-mail: drreyaz07@rediffmail.com

Research ethics: The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).
Informed consent: Informed consent was obtained from legal guardians.
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: The authors state no conflict of interest.
Research funding: None declared.
Data availability: Not applicable.

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Received: 2023-12-08

Accepted: 2024-02-18

Published Online: 2024-03-07

Published in Print: 2024-05-27

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Articles in the same Issue

https://doi.org/10.1515/jpem-2023-0541

Keywords for this article

combined pituitary hormone deficiency; central diabetes insipidus; pituitary stalk interruption syndrome; roundabout receptor-1 gene