A Novel De novo Heterozygous Mutation in the SON Gene Associated with Septo-optic Dysplasia: A New Phenotype

Abstract

Septo-optic dysplasia (SOD) syndrome is a rare congenital disorder characterized by a classic triad of optic nerve/chiasm hypoplasia, agenesis of septum pellucidum and corpus callosum, and hypoplasia of the hypothalamic-pituitary axis.

Herein, we report the clinical case of 2-year-old boy presenting with psychomotor delay, nystagmus, congenital hypothyroidism, and a clinically relevant growth delay. The neuroradiological examination showed partial segmental agenesis of the corpus callosum, agenesis of the septum pellucidum, optic nerve hypoplasia, and a small pituitary gland with a small median pituitary stalk. A whole-exome sequencing analysis detected a novel heterozygous de novo variant c.1069_1070delAG in SON, predicted as likely pathogenic.

To date, SON pathogenic variants have been described as responsible for Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome, a multisystemic neurodevelopmental disorder mainly characterized by intellectual disability, facial dysmorphisms, visual abnormalities, brain malformations, feeding difficulties, and growth delay. The herein described case is the first recognized clinic-radiological occurrence of SOD syndrome with hypothalamic-pituitary dysfunction in a patient carrying a SON gene variant, considered responsible of ZTTK syndrome, suggesting a possible relationship between SOD and SON gene alterations, never described so far, making the search for SON gene mutations advisable in patients with SOD.

Keywords

septo-optic dysplasia - Zhu-Tokita-Takenouchi-Kim syndrome - SON gene

Statement of Ethics

Parents of the subject have given their written informed consent for publication of the case and related images.

Authors' Contribution

R.R., A.C., and L.P. conceptualized and designed the study; L.P., A.C., M.C.V., C.B., M.A., G.K., G.P., G.V., R.N., and R.R. collected data; L.P., A.C., E.P., D.P., M.C.V., C.B., M.A., G.K., G.P., G.V., R.N., and R.R. contributed to analysis and interpretation of results; L.P., A.C., E.P., D.P., M.C.V., C.B., and R.R. drafted manuscript preparation. All authors reviewed the results and approved the final version of the manuscript.

Publikationsverlauf

Eingereicht: 02. Mai 2023

Angenommen: 19. Juni 2023

Accepted Manuscript online:
21. Juni 2023

Artikel online veröffentlicht:
10. August 2023

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