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Case Report: Pallister-Hall syndrome associated with a previously unreported de novo GLI3 frameshift variant and diagnostic insights from the Middle East

Year: 2026

Type: article

Abstract: Pallister–Hall syndrome (PHS) is a rare GLI3 -related disorder characterized by hypothalamic hamartoma and mesoaxial polydactyly. We report an infant from the West Bank, Palestine, with these cardinal findings, imperforate anus, rhizomelic limb shortening, right renal agenesis, choanal atresia, and an ostium secundum atrial septal defect. Whole-exome sequencing identified a previously unreported heterozygous GLI3 frameshift variant, NM_000168.6:c.2410del (p.Val804SerfsTer5), absent in both parents and therefore presumed de novo . The variant lies in the middle-third PHS-associated region and was provisionally classified as likely pathogenic. At the last documented assessment on day 89 of life, no seizures or biochemical evidence of pituitary dysfunction had been identified. Comparison with regional and molecularly relevant reports showed that neurological and endocrine severity varied among patients with truncating variants in this region. This case documents a previously unreported likely pathogenic GLI3 variant in an established PHS phenotype and supports age-appropriate neurological and endocrine surveillance.

Source: Frontiers in Pediatrics

DOI: 10.3389/fped.2026.1818628

Authors: Gessila Khalil, Ihab K. Hemieid, Elie G. Malki

Institution: Al-Quds University

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: $3,801