Case Report: Pallister-Hall syndrome associated with a previously unreported de novo GLI3 frameshift variant and diagnostic insights from the Middle East
- 1Faculty of Medicine, Al-Quds University , ,
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.
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BibTeX
@article{khalil2026case,
title = {{Case Report: Pallister-Hall syndrome associated with a previously unreported de novo GLI3 frameshift variant and diagnostic insights from the Middle East}},
author = {Gessila Khalil and Ihab K. Hemieid and Elie G. Malki},
journal = {Frontiers in pediatrics},
year = {2026},
month = oct,
doi = {10.3389/fped.2026.1818628},
url = {https://europepmc.org/article/PMC/PMC13719475},
note = {CC BY},
}
RIS
TY - JOUR
TI - Case Report: Pallister-Hall syndrome associated with a previously unreported de novo GLI3 frameshift variant and diagnostic insights from the Middle East
AU - Gessila Khalil
AU - Ihab K. Hemieid
AU - Elie G. Malki
PY - 2026
DA - 2026/10/16
JO - Frontiers in pediatrics
DO - 10.3389/fped.2026.1818628
UR - https://europepmc.org/article/PMC/PMC13719475
AB - 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.
SN - 2296-2360
ER -