Work

De Novo GLI2 Missense Variant in a Child With Isolated Hypopituitarism and Craniofacial Anomalies: Expanding the Phenotypic Spectrum

Year: 2025

Type: article

Abstract: BACKGROUND: Culler-Jones syndrome (CJS) is an autosomal dominant disorder characterized by hypopituitarism, postaxial polydactyly, and craniofacial anomalies, associated with pathogenic GLI2 variants. Genotype-phenotype correlations suggest missense variants may present with isolated pituitary phenotypes. METHODS: We evaluated an 8-year-old boy referred for short stature, failure to thrive, and neurodevelopmental concerns. Clinical assessment, endocrine evaluation, imaging studies, and trio exome sequencing were performed. RESULTS: The patient exhibited growth hormone deficiency, dolichocephaly, midline diastema, lip and tongue ties, hypotonia, and ADHD. No polydactyly was noted. Trio exome sequencing revealed a de novo heterozygous likely pathogenic GLI2 variant (c.1496G>T; p.Arg499Leu) located within the DNA-binding zinc finger domain. CONCLUSION: This case expands the phenotypic spectrum of GLI2-related disorders and reinforces that non-truncating GLI2 variants are often associated with isolated hypopituitarism and subtle craniofacial or neurodevelopmental features. Genomic testing should be considered in similar clinical presentations.

Source: Molecular Genetics & Genomic Medicine

DOI: 10.1002/mgg3.70136

Authors: Himanshu Goel, Katrina Harrison

Institutions: Hunter Genetics, University of Newcastle Australia

Language: English

Topic: Genomics and Rare Diseases

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,900