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Clinical delineation of 18q11‐q12 microdeletion: Intellectual disability, speech and behavioral disorders, and conotruncal heart defects

BACKGROUND: Since the establishment of chromosomal microarrays in clinical practice, many new microdeletion/microduplication syndromes have been identified, including 18q11.2 microdeletion. Chromosome 18q deletion syndrome is commonly classified into distal deletion and a much rarer proximal interst...

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Autores principales: Rojnueangnit, Kitiwan, Charalsawadi, Chariyawan, Thammachote, Weerin, Pradabmuksiri, Ariya, Tim‐Aroon, Thipwimol, Novelli, Antonio, Loddo, Sara, Briuglia, Silvana, Concetta, Cutrupi M., Wattanasirichaigoon, Duangrurdee, Jinawath, Natini
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732287/
https://www.ncbi.nlm.nih.gov/pubmed/31390163
http://dx.doi.org/10.1002/mgg3.896
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author Rojnueangnit, Kitiwan
Charalsawadi, Chariyawan
Thammachote, Weerin
Pradabmuksiri, Ariya
Tim‐Aroon, Thipwimol
Novelli, Antonio
Loddo, Sara
Briuglia, Silvana
Concetta, Cutrupi M.
Wattanasirichaigoon, Duangrurdee
Jinawath, Natini
author_facet Rojnueangnit, Kitiwan
Charalsawadi, Chariyawan
Thammachote, Weerin
Pradabmuksiri, Ariya
Tim‐Aroon, Thipwimol
Novelli, Antonio
Loddo, Sara
Briuglia, Silvana
Concetta, Cutrupi M.
Wattanasirichaigoon, Duangrurdee
Jinawath, Natini
author_sort Rojnueangnit, Kitiwan
collection PubMed
description BACKGROUND: Since the establishment of chromosomal microarrays in clinical practice, many new microdeletion/microduplication syndromes have been identified, including 18q11.2 microdeletion. Chromosome 18q deletion syndrome is commonly classified into distal deletion and a much rarer proximal interstitial deletion spanning the 18q11.2‐q21.1 region. METHODS: We report two new patients and review 27 additional cases in DECIPHER/ClinGen databases and four cases from the literature, with more proximal 18q deletions involving 18q11‐q12 (band 1 only; 17.2–43.5 Mb position) deletion. RESULTS: Common presentations of 18q11‐q12 deletions include developmental delay/intellectual disability (DD/ID) (82%); speech delay/autism/attention deficit and hyperactivity/other behavioral problems (30%); conotruncal heart defects (15%); and subtle/non‐specific facial dysmorphism. The deletion in four out of five cases with cardiac defect was distal to GATA6, suggesting an alternative mechanism other than haploinsufficiency of GATA6 as an underlying cause of cardiac malformations. Precocious puberty with advanced skeletal age was first observed in one patient, suggesting a unique and expanded phenotype of proximal 18q deletion. When comparing genotype–phenotype correlations from the present study with previous reports, the critical regions for selected phenotypes of 18q11‐q12 deletion syndrome could be narrowed down as follows: 38.8–43.5 Mb for moderate to severe DD/ID, 19.6–24.4 Mb and 26.9–28.6 Mb for conotruncal heart defect. CONCLUSION: The detailed clinical delineation of the proximal 18q deletions identified in this study should contribute to better understanding of the genotype–phenotype correlations and better long‐term care of patients with this rare syndrome.
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spelling pubmed-67322872019-09-12 Clinical delineation of 18q11‐q12 microdeletion: Intellectual disability, speech and behavioral disorders, and conotruncal heart defects Rojnueangnit, Kitiwan Charalsawadi, Chariyawan Thammachote, Weerin Pradabmuksiri, Ariya Tim‐Aroon, Thipwimol Novelli, Antonio Loddo, Sara Briuglia, Silvana Concetta, Cutrupi M. Wattanasirichaigoon, Duangrurdee Jinawath, Natini Mol Genet Genomic Med Original Articles BACKGROUND: Since the establishment of chromosomal microarrays in clinical practice, many new microdeletion/microduplication syndromes have been identified, including 18q11.2 microdeletion. Chromosome 18q deletion syndrome is commonly classified into distal deletion and a much rarer proximal interstitial deletion spanning the 18q11.2‐q21.1 region. METHODS: We report two new patients and review 27 additional cases in DECIPHER/ClinGen databases and four cases from the literature, with more proximal 18q deletions involving 18q11‐q12 (band 1 only; 17.2–43.5 Mb position) deletion. RESULTS: Common presentations of 18q11‐q12 deletions include developmental delay/intellectual disability (DD/ID) (82%); speech delay/autism/attention deficit and hyperactivity/other behavioral problems (30%); conotruncal heart defects (15%); and subtle/non‐specific facial dysmorphism. The deletion in four out of five cases with cardiac defect was distal to GATA6, suggesting an alternative mechanism other than haploinsufficiency of GATA6 as an underlying cause of cardiac malformations. Precocious puberty with advanced skeletal age was first observed in one patient, suggesting a unique and expanded phenotype of proximal 18q deletion. When comparing genotype–phenotype correlations from the present study with previous reports, the critical regions for selected phenotypes of 18q11‐q12 deletion syndrome could be narrowed down as follows: 38.8–43.5 Mb for moderate to severe DD/ID, 19.6–24.4 Mb and 26.9–28.6 Mb for conotruncal heart defect. CONCLUSION: The detailed clinical delineation of the proximal 18q deletions identified in this study should contribute to better understanding of the genotype–phenotype correlations and better long‐term care of patients with this rare syndrome. John Wiley and Sons Inc. 2019-08-07 /pmc/articles/PMC6732287/ /pubmed/31390163 http://dx.doi.org/10.1002/mgg3.896 Text en © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Rojnueangnit, Kitiwan
Charalsawadi, Chariyawan
Thammachote, Weerin
Pradabmuksiri, Ariya
Tim‐Aroon, Thipwimol
Novelli, Antonio
Loddo, Sara
Briuglia, Silvana
Concetta, Cutrupi M.
Wattanasirichaigoon, Duangrurdee
Jinawath, Natini
Clinical delineation of 18q11‐q12 microdeletion: Intellectual disability, speech and behavioral disorders, and conotruncal heart defects
title Clinical delineation of 18q11‐q12 microdeletion: Intellectual disability, speech and behavioral disorders, and conotruncal heart defects
title_full Clinical delineation of 18q11‐q12 microdeletion: Intellectual disability, speech and behavioral disorders, and conotruncal heart defects
title_fullStr Clinical delineation of 18q11‐q12 microdeletion: Intellectual disability, speech and behavioral disorders, and conotruncal heart defects
title_full_unstemmed Clinical delineation of 18q11‐q12 microdeletion: Intellectual disability, speech and behavioral disorders, and conotruncal heart defects
title_short Clinical delineation of 18q11‐q12 microdeletion: Intellectual disability, speech and behavioral disorders, and conotruncal heart defects
title_sort clinical delineation of 18q11‐q12 microdeletion: intellectual disability, speech and behavioral disorders, and conotruncal heart defects
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732287/
https://www.ncbi.nlm.nih.gov/pubmed/31390163
http://dx.doi.org/10.1002/mgg3.896
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