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Neuromuscular and Neuroendocrinological Features Associated With ZC4H2-Related Arthrogryposis Multiplex Congenita in a Sicilian Family: A Case Report

Wieacker-Wolff syndrome (WWS) is an X-linked Arthrogryposis Multiplex Congenita (AMC) disorder associated with broad neurodevelopmental impairment. The genetic basis of WWS lies in hemizygous pathogenic variants in ZC4H2, encoding a C4H2 type zinc-finger nuclear factor abundantly expressed in the de...

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Autores principales: Piccolo, Gianluca, d'Annunzio, Giuseppe, Amadori, Elisabetta, Riva, Antonella, Borgia, Paola, Tortora, Domenico, Maghnie, Mohamad, Minetti, Carlo, Gitto, Eloisa, Iacomino, Michele, Baldassari, Simona, Fiorillo, Chiara, Zara, Federico, Striano, Pasquale, Salpietro, Vincenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313121/
https://www.ncbi.nlm.nih.gov/pubmed/34322088
http://dx.doi.org/10.3389/fneur.2021.704747
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author Piccolo, Gianluca
d'Annunzio, Giuseppe
Amadori, Elisabetta
Riva, Antonella
Borgia, Paola
Tortora, Domenico
Maghnie, Mohamad
Minetti, Carlo
Gitto, Eloisa
Iacomino, Michele
Baldassari, Simona
Fiorillo, Chiara
Zara, Federico
Striano, Pasquale
Salpietro, Vincenzo
author_facet Piccolo, Gianluca
d'Annunzio, Giuseppe
Amadori, Elisabetta
Riva, Antonella
Borgia, Paola
Tortora, Domenico
Maghnie, Mohamad
Minetti, Carlo
Gitto, Eloisa
Iacomino, Michele
Baldassari, Simona
Fiorillo, Chiara
Zara, Federico
Striano, Pasquale
Salpietro, Vincenzo
author_sort Piccolo, Gianluca
collection PubMed
description Wieacker-Wolff syndrome (WWS) is an X-linked Arthrogryposis Multiplex Congenita (AMC) disorder associated with broad neurodevelopmental impairment. The genetic basis of WWS lies in hemizygous pathogenic variants in ZC4H2, encoding a C4H2 type zinc-finger nuclear factor abundantly expressed in the developing human brain. The main clinical features described in WWS families carrying ZC4H2 pathogenic variants encompass having a short stature, microcephaly, birth respiratory distress, arthrogryposis, hypotonia, distal muscle weakness, and broad neurodevelopmental delay. We hereby report a Sicilian family with a boy clinically diagnosed with WWS and genetically investigated with exome sequencing (ES), leading to the identification of a c.593G>A (p. R198Q) hemizygous pathogenic variant in the ZC4H2 gene. During the first year of life, the onset of central hypoadrenalism led to recurrent hypoglycemic events, which likely contributed to seizure susceptibility. Also, muscle biopsy studies confirmed a pathology of the muscle tissue and revealed peculiar abnormalities of the neuromuscular junction. In conclusion, we expand the phenotypic spectrum of the WWS-related neurodevelopmental disorders and discuss the role of ZC4H2 in the context of the potential neuroendocrinological and neuromuscular features associated with this condition.
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spelling pubmed-83131212021-07-27 Neuromuscular and Neuroendocrinological Features Associated With ZC4H2-Related Arthrogryposis Multiplex Congenita in a Sicilian Family: A Case Report Piccolo, Gianluca d'Annunzio, Giuseppe Amadori, Elisabetta Riva, Antonella Borgia, Paola Tortora, Domenico Maghnie, Mohamad Minetti, Carlo Gitto, Eloisa Iacomino, Michele Baldassari, Simona Fiorillo, Chiara Zara, Federico Striano, Pasquale Salpietro, Vincenzo Front Neurol Neurology Wieacker-Wolff syndrome (WWS) is an X-linked Arthrogryposis Multiplex Congenita (AMC) disorder associated with broad neurodevelopmental impairment. The genetic basis of WWS lies in hemizygous pathogenic variants in ZC4H2, encoding a C4H2 type zinc-finger nuclear factor abundantly expressed in the developing human brain. The main clinical features described in WWS families carrying ZC4H2 pathogenic variants encompass having a short stature, microcephaly, birth respiratory distress, arthrogryposis, hypotonia, distal muscle weakness, and broad neurodevelopmental delay. We hereby report a Sicilian family with a boy clinically diagnosed with WWS and genetically investigated with exome sequencing (ES), leading to the identification of a c.593G>A (p. R198Q) hemizygous pathogenic variant in the ZC4H2 gene. During the first year of life, the onset of central hypoadrenalism led to recurrent hypoglycemic events, which likely contributed to seizure susceptibility. Also, muscle biopsy studies confirmed a pathology of the muscle tissue and revealed peculiar abnormalities of the neuromuscular junction. In conclusion, we expand the phenotypic spectrum of the WWS-related neurodevelopmental disorders and discuss the role of ZC4H2 in the context of the potential neuroendocrinological and neuromuscular features associated with this condition. Frontiers Media S.A. 2021-07-12 /pmc/articles/PMC8313121/ /pubmed/34322088 http://dx.doi.org/10.3389/fneur.2021.704747 Text en Copyright © 2021 Piccolo, d'Annunzio, Amadori, Riva, Borgia, Tortora, Maghnie, Minetti, Gitto, Iacomino, Baldassari, Fiorillo, Zara, Striano and Salpietro. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Piccolo, Gianluca
d'Annunzio, Giuseppe
Amadori, Elisabetta
Riva, Antonella
Borgia, Paola
Tortora, Domenico
Maghnie, Mohamad
Minetti, Carlo
Gitto, Eloisa
Iacomino, Michele
Baldassari, Simona
Fiorillo, Chiara
Zara, Federico
Striano, Pasquale
Salpietro, Vincenzo
Neuromuscular and Neuroendocrinological Features Associated With ZC4H2-Related Arthrogryposis Multiplex Congenita in a Sicilian Family: A Case Report
title Neuromuscular and Neuroendocrinological Features Associated With ZC4H2-Related Arthrogryposis Multiplex Congenita in a Sicilian Family: A Case Report
title_full Neuromuscular and Neuroendocrinological Features Associated With ZC4H2-Related Arthrogryposis Multiplex Congenita in a Sicilian Family: A Case Report
title_fullStr Neuromuscular and Neuroendocrinological Features Associated With ZC4H2-Related Arthrogryposis Multiplex Congenita in a Sicilian Family: A Case Report
title_full_unstemmed Neuromuscular and Neuroendocrinological Features Associated With ZC4H2-Related Arthrogryposis Multiplex Congenita in a Sicilian Family: A Case Report
title_short Neuromuscular and Neuroendocrinological Features Associated With ZC4H2-Related Arthrogryposis Multiplex Congenita in a Sicilian Family: A Case Report
title_sort neuromuscular and neuroendocrinological features associated with zc4h2-related arthrogryposis multiplex congenita in a sicilian family: a case report
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313121/
https://www.ncbi.nlm.nih.gov/pubmed/34322088
http://dx.doi.org/10.3389/fneur.2021.704747
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