Clinical delineation of 18q11-q12 microdeletion

Intellectual disability, speech and behavioral disorders, and conotruncal heart defects

Kitiwan Rojnueangnit, Chariyawan Charalsawadi, Weerin Thammachote, Ariya Pradabmuksiri, Thipwimol Tim-Aroon, Antonio Novelli, Sara Loddo, Silvana Briuglia, Cutrupi M Concetta, Duangrurdee Wattanasirichaigoon, Natini Jinawath

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)e896
JournalMolecular genetics & genomic medicine
Volume7
Issue number9
DOIs
Publication statusPublished - Sep 2019

Fingerprint

Speech Disorders
Intellectual Disability
Genetic Association Studies
Language Development Disorders
Phenotype
Precocious Puberty
Haploinsufficiency
Long-Term Care
Autistic Disorder
Databases

Cite this

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.

In: Molecular genetics & genomic medicine, Vol. 7, No. 9, 09.2019, p. e896.

Research output: Contribution to journalArticle

Rojnueangnit, K, Charalsawadi, C, Thammachote, W, Pradabmuksiri, A, Tim-Aroon, T, Novelli, A, Loddo, S, Briuglia, S, Concetta, CM, Wattanasirichaigoon, D & Jinawath, N 2019, 'Clinical delineation of 18q11-q12 microdeletion: Intellectual disability, speech and behavioral disorders, and conotruncal heart defects', Molecular genetics & genomic medicine, vol. 7, no. 9, pp. e896. https://doi.org/10.1002/mgg3.896
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. In: Molecular genetics & genomic medicine. 2019 ; Vol. 7, No. 9. pp. e896.
@article{dbffd1aace61411c9a8d74d2ca704462,
title = "Clinical delineation of 18q11-q12 microdeletion: Intellectual disability, speech and behavioral disorders, and conotruncal heart defects",
abstract = "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.",
author = "Kitiwan Rojnueangnit and Chariyawan Charalsawadi and Weerin Thammachote and Ariya Pradabmuksiri and Thipwimol Tim-Aroon and Antonio Novelli and Sara Loddo and Silvana Briuglia and Concetta, {Cutrupi M} and Duangrurdee Wattanasirichaigoon and Natini Jinawath",
note = "{\circledC} 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.",
year = "2019",
month = "9",
doi = "10.1002/mgg3.896",
language = "English",
volume = "7",
pages = "e896",
journal = "Molecular genetics & genomic medicine",
issn = "2324-9269",
publisher = "John Wiley and Sons Inc.",
number = "9",

}

TY - JOUR

T1 - Clinical delineation of 18q11-q12 microdeletion

T2 - Intellectual disability, speech and behavioral disorders, and conotruncal heart defects

AU - Rojnueangnit, Kitiwan

AU - Charalsawadi, Chariyawan

AU - Thammachote, Weerin

AU - Pradabmuksiri, Ariya

AU - Tim-Aroon, Thipwimol

AU - Novelli, Antonio

AU - Loddo, Sara

AU - Briuglia, Silvana

AU - Concetta, Cutrupi M

AU - Wattanasirichaigoon, Duangrurdee

AU - Jinawath, Natini

N1 - © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

PY - 2019/9

Y1 - 2019/9

N2 - 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.

AB - 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.

U2 - 10.1002/mgg3.896

DO - 10.1002/mgg3.896

M3 - Article

VL - 7

SP - e896

JO - Molecular genetics & genomic medicine

JF - Molecular genetics & genomic medicine

SN - 2324-9269

IS - 9

ER -