Work

New Pathogenic Variant in the GLI3 Gene in the First Colombian Patient Associated With Pallister‐Hall Syndrome: A Clinical Report

Year: 2025

Type: article

Abstract: BACKGROUND: Pallister-Hall syndrome (PHS) is an extremely rare genetic disorder. It presents as a polymalformative syndrome affecting craniofacial structures, the central nervous system, limbs, various internal organs, and the endocrine system. It is considered a ciliopathy, as it is associated with loss-of-function variants in the GLI3 gene, a transcription factor essential for primary cilium signaling. The syndrome shows marked clinical heterogeneity depending on the type of genetic variant, which makes diagnosis challenging. It is usually suspected at an early age when a hypothalamic hamartoma is associated with polydactyly. Endocrine manifestations are often linked to the hamartoma, further complicating diagnosis. CASE PRESENTATION: A 23-year-old Colombian patient presented with a history of hypothalamic hamartoma, gelastic seizures, postaxial polydactyly of hands and feet, and craniofacial dysmorphisms. Physical examination revealed dolichocephaly, bilateral epicanthus, broad nasal bridge, short and broad neck, mild cervical kyphosis, mild scoliosis, micrognathia, bilateral ulnar deviation of the fourth and fifth fingers, and overlapping toes on both feet. No genital anomalies were found. Neuropsychological evaluation reported a borderline intellectual quotient of 78. Whole-exome sequencing identified a de novo heterozygous pathogenic variant in GLI3 (c.2151del; p.(Gln71HisfsTer16)), confirmed by Sanger sequencing. CONCLUSIONS: We report the first case described in Colombia of a previously unreported truncating genetic variant. We performed a clinical-molecular correlation in a 23-year-old adult whose diagnosis of PHS was delayed until adulthood, years after the initial identification of a hypothalamic hamartoma, refractory gelastic seizures, polydactyly, and mild cognitive impairment. This case broadens the clinical spectrum regarding the viability of patients with PHS into adulthood, showing that it is not restricted to the severe neonatal or infantile presentations classically described.

Source: Molecular Genetics & Genomic Medicine

DOI: 10.1002/mgg3.70146

Authors: Sebastián Bonilla‐Navarrete, Luis Eduardo Prieto, Laura Valentina Carvajal, Jorge Andrés Olave‐Rodríguez, Lisa Ximena Rodriguez‐Rojas, Jose Antonio Nastasi‐Catanese

Institutions: Fundación Valle del Lili, Icesi University

Language: English

Topic: Genetic and Kidney Cyst 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