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The Expanding Phenotype of ZTTK Syndrome Due to the Heterozygous Variant of SON Gene Focusing on Liver Involvement: Patient Report and Literature Review

Zhu–Tokita–Takenouchi–Kim (ZTTK) syndrome, an intellectual disability syndrome first described in 2016, is caused by heterozygous loss-of-function variants in SON. Haploinsufficiency in SON may affect multiple genes, including those involved in the development and metabolism of multiple organs. Cons...

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Autores principales: Pietrobattista, Andrea, Della Volpe, Luca, Francalanci, Paola, Figà Talamanca, Lorenzo, Monti, Lidia, Lepri, Francesca Romana, Basso, Maria Sole, Liccardo, Daniela, Della Corte, Claudia, Mosca, Antonella, Alterio, Tommaso, Veraldi, Silvio, Callea, Francesco, Novelli, Antonio, Maggiore, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048019/
https://www.ncbi.nlm.nih.gov/pubmed/36981010
http://dx.doi.org/10.3390/genes14030739
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author Pietrobattista, Andrea
Della Volpe, Luca
Francalanci, Paola
Figà Talamanca, Lorenzo
Monti, Lidia
Lepri, Francesca Romana
Basso, Maria Sole
Liccardo, Daniela
Della Corte, Claudia
Mosca, Antonella
Alterio, Tommaso
Veraldi, Silvio
Callea, Francesco
Novelli, Antonio
Maggiore, Giuseppe
author_facet Pietrobattista, Andrea
Della Volpe, Luca
Francalanci, Paola
Figà Talamanca, Lorenzo
Monti, Lidia
Lepri, Francesca Romana
Basso, Maria Sole
Liccardo, Daniela
Della Corte, Claudia
Mosca, Antonella
Alterio, Tommaso
Veraldi, Silvio
Callea, Francesco
Novelli, Antonio
Maggiore, Giuseppe
author_sort Pietrobattista, Andrea
collection PubMed
description Zhu–Tokita–Takenouchi–Kim (ZTTK) syndrome, an intellectual disability syndrome first described in 2016, is caused by heterozygous loss-of-function variants in SON. Haploinsufficiency in SON may affect multiple genes, including those involved in the development and metabolism of multiple organs. Considering the broad spectrum of SON functions, it is to be expected that pathogenic variants in this gene can cause a wide spectrum of clinical symptoms. We present an additional ZTTK syndrome case due to a de novo heterozygous variant in the SON gene (c.5751_5754delAGTT). The clinical manifestations of our patient were similar to those present in previously reported cases; however, the diagnosis of ZTTK syndrome was delayed for a long time and was carried out during the diagnostic work-up of significant chronic liver disease (CLD). CLD has not yet been reported in any series; therefore, our report provides new information on this rare condition and suggests the expansion of the ZTTK syndrome phenotype, including possible liver involvement. Correspondingly, we recommend screening patients with SON variants specifically for liver involvement from the first years of life. Once the CLD has been diagnosed, an appropriate follow-up is mandatory, especially considering the role of SON as an emerging player in cancer development. Further studies are needed to investigate the role of SON haploinsufficiency as a downregulator of essential genes, thus potentially impairing the normal development and/or functions of multiple organs.
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spelling pubmed-100480192023-03-29 The Expanding Phenotype of ZTTK Syndrome Due to the Heterozygous Variant of SON Gene Focusing on Liver Involvement: Patient Report and Literature Review Pietrobattista, Andrea Della Volpe, Luca Francalanci, Paola Figà Talamanca, Lorenzo Monti, Lidia Lepri, Francesca Romana Basso, Maria Sole Liccardo, Daniela Della Corte, Claudia Mosca, Antonella Alterio, Tommaso Veraldi, Silvio Callea, Francesco Novelli, Antonio Maggiore, Giuseppe Genes (Basel) Case Report Zhu–Tokita–Takenouchi–Kim (ZTTK) syndrome, an intellectual disability syndrome first described in 2016, is caused by heterozygous loss-of-function variants in SON. Haploinsufficiency in SON may affect multiple genes, including those involved in the development and metabolism of multiple organs. Considering the broad spectrum of SON functions, it is to be expected that pathogenic variants in this gene can cause a wide spectrum of clinical symptoms. We present an additional ZTTK syndrome case due to a de novo heterozygous variant in the SON gene (c.5751_5754delAGTT). The clinical manifestations of our patient were similar to those present in previously reported cases; however, the diagnosis of ZTTK syndrome was delayed for a long time and was carried out during the diagnostic work-up of significant chronic liver disease (CLD). CLD has not yet been reported in any series; therefore, our report provides new information on this rare condition and suggests the expansion of the ZTTK syndrome phenotype, including possible liver involvement. Correspondingly, we recommend screening patients with SON variants specifically for liver involvement from the first years of life. Once the CLD has been diagnosed, an appropriate follow-up is mandatory, especially considering the role of SON as an emerging player in cancer development. Further studies are needed to investigate the role of SON haploinsufficiency as a downregulator of essential genes, thus potentially impairing the normal development and/or functions of multiple organs. MDPI 2023-03-17 /pmc/articles/PMC10048019/ /pubmed/36981010 http://dx.doi.org/10.3390/genes14030739 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Pietrobattista, Andrea
Della Volpe, Luca
Francalanci, Paola
Figà Talamanca, Lorenzo
Monti, Lidia
Lepri, Francesca Romana
Basso, Maria Sole
Liccardo, Daniela
Della Corte, Claudia
Mosca, Antonella
Alterio, Tommaso
Veraldi, Silvio
Callea, Francesco
Novelli, Antonio
Maggiore, Giuseppe
The Expanding Phenotype of ZTTK Syndrome Due to the Heterozygous Variant of SON Gene Focusing on Liver Involvement: Patient Report and Literature Review
title The Expanding Phenotype of ZTTK Syndrome Due to the Heterozygous Variant of SON Gene Focusing on Liver Involvement: Patient Report and Literature Review
title_full The Expanding Phenotype of ZTTK Syndrome Due to the Heterozygous Variant of SON Gene Focusing on Liver Involvement: Patient Report and Literature Review
title_fullStr The Expanding Phenotype of ZTTK Syndrome Due to the Heterozygous Variant of SON Gene Focusing on Liver Involvement: Patient Report and Literature Review
title_full_unstemmed The Expanding Phenotype of ZTTK Syndrome Due to the Heterozygous Variant of SON Gene Focusing on Liver Involvement: Patient Report and Literature Review
title_short The Expanding Phenotype of ZTTK Syndrome Due to the Heterozygous Variant of SON Gene Focusing on Liver Involvement: Patient Report and Literature Review
title_sort expanding phenotype of zttk syndrome due to the heterozygous variant of son gene focusing on liver involvement: patient report and literature review
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048019/
https://www.ncbi.nlm.nih.gov/pubmed/36981010
http://dx.doi.org/10.3390/genes14030739
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