Congenital Glaucoma in Patients with Neonatal Diabetes and Congenital Hypothyroidism (NDH) Syndrome

Introduction

Neonatal diabetes and congenital hypothyroidism (NDH) syndrome is a rare condition caused by autosomal recessive mutations in the GLI-similar 3 (GLIS3) gene [1]. The human GLIS3 gene is located on chromosome 9p24.2 and encodes the Krüppel-like zinc finger transcription factor GLIS3 that is expressed during early embryogenesis [2]. It is implicated in the development of many organs, including the pancreas, kidneys, and eyes [2]. NDH syndrome was initially described in 2003, and the underlying GLIS3 mutations were identified in 2006 [3]. Since then, about 20 cases of NDH syndrome have been reported, with considerable phenotypic variability [1]. Although some affected individuals have died in early childhood, there are case reports of patients who survived into adulthood [4].

Apart from neonatal diabetes and congenital hypothyroidism, reported patients suffered from intrauterine growth retardation, developmental delay, hearing disorder, cardiac disorders, anaemia, cholestasis, liver fibrosis, megalocornea or glaucoma [4].

A recent case series involving 12 patients with NDH syndrome reported that intrauterine growth retardation and developmental delay were consistent features across all cases [5]. Nine of these 12 patients were born to parents who were first cousins. Notably, only 4 out of the 12 patients were diagnosed with congenital glaucoma (CG), suggesting variability in ocular manifestations [5].

To date, no specific exon of the GLIS3 gene has been conclusively associated with the development of CG in NDH syndrome, underscoring the need for further investigations [5]. We present the case of two cousins, each born to parents who were first cousins. The parents of one child were siblings of the parents of the other.

Publication History

Received: 25 May 2025

Accepted: 20 August 2025

Article published online:
17 October 2025

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