Expanding the Genetic and Clinical Spectrum of GZF1-Related Phenotype: A Specific Ocular and Skeletal Disorder Distinguishable From Larsen Syndrome
Por:
Yokoyama-Rebollar E., Villarroel C.E., Barragán-Arévalo T., Chacón-Camacho O.F., Orozco-Ávila D.C., Leal-Anaya P., Del Castillo-Ruiz V., Zenteno J.C.
Publicada:
1 ene 2026
Ahead of Print:
1 may 2026
Resumen:
© 2026 Wiley Periodicals LLC.GZF1-related phenotype (GZF1RP) has been referred to by different names, including autosomal recessive Larsen syndrome (LRS) and “joint laxity, short stature, and myopia”. Only ten patients from five families have been reported, all of whom carry biallelic variants of GZF1. They share short stature and joint dislocation with LRS; however, they present with severe ocular manifestations, suggesting that GZF1RP may be specific. In this study, we described three new patients with severe ophthalmologic phenotypes, including congenital glaucoma and abnormal iris morphology. We identified the GZF1: c.1440del (p.His481IlefsTer26) variant in homozygosity in two affected sisters and compound heterozygosity in the third patient: the same c.1440del plus c.1451_1452del (p.Cys484fs). In addition to expanding the molecular spectrum, we identified new radiological findings, such as cervical segmentation defects, carpal shortening, and lower lumbar sacralization, as well as some clinical findings uncommon in previous cases, such as umbilical hernia and congenital heart disease. We also searched for LRS case series with pathogenic variants in FLNB to identify differences between the two entities. The comparison allows us to define a recognizable GZF1RP that includes severe ocular defects, short stature, facial dysmorphism, joint hypermobility/dislocations, scoliosis, thoracic deformity, progressive hearing loss, umbilical hernia, and hypodontia.
Filiaciones:
Yokoyama-Rebollar E.:
Human Genetics Department, National Institute of Pediatrics, Mexico City, Mexico
Villarroel C.E.:
Human Genetics Department, National Institute of Pediatrics, Mexico City, Mexico
Barragán-Arévalo T.:
Genetics Department, Hospital Infantil de México “Federico Gómez”, Mexico City, Mexico
Chacón-Camacho O.F.:
Department of Genetics, Institute of Ophthalmology “Conde de Valenciana”, Mexico City, Mexico
Laboratorio 5-Genética, Edificio 4-A, Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, UNAM, Mexico City, Mexico
Orozco-Ávila D.C.:
Human Genetics Department, National Institute of Pediatrics, Mexico City, Mexico
Leal-Anaya P.:
Human Genetics Department, National Institute of Pediatrics, Mexico City, Mexico
Del Castillo-Ruiz V.:
Human Genetics Department, National Institute of Pediatrics, Mexico City, Mexico
Zenteno J.C.:
Department of Genetics, Institute of Ophthalmology “Conde de Valenciana”, Mexico City, Mexico
Rare Diseases Diagnostic Unit and Department of Biochemistry, Faculty of Medicine, UNAM, Mexico City, Mexico
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