Expanding the Genetic and Clinical Spectrum of GZF1-Related Phenotype: A Specific Ocular and Skeletal Disorder Distinguishable From Larsen Syndrome

Pathogenic GZF1 variants (GDNF zinc finger transcription factor), skeletal and ocular dysmorphogenesis

This study expands the clinical and genetic spectrum of GZF1-related syndrome, a GDNF zinc finger transcription factor involved in GDNF signaling. New cases are described with biallelic pathogenic variants, confirming a characteristic ocular and skeletal phenotype — including severe myopia, ptosis, joint contractures, and vertebral anomalies — distinguishable from Larsen syndrome despite phenotypic overlaps. The study clarifies differential diagnostic criteria and reinforces GZF1 as a rare but clinically recognizable gene.

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GZF1 is a rare gene whose phenotype can be confused with Larsen syndrome (FLNB) due to shared skeletal anomalies. This precise phenotypic clarification is practically useful for directing targeted sequencing and interpreting VUS in the context of skeletal-ocular presentations.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 1/2 · Sample size: 1/1 · Publication status: 1/1 → Total: 7/10