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Delineamento clínico da microdeleção de 18q11-q12: deficiência intelectual, distúrbios da fala e do comportamento e defeitos cardíacos conotruncais



Desde o estabelecimento de microarranjos cromossômicos na prática clínica, muitas novas síndromes de microdeleção / microduplicação foram identificadas, incluindo a microdeleção de 18q11.2. A síndrome de deleção do cromossomo 18q é comumente classificada em deleção distal e uma deleção intersticial proximal muito mais rara, abrangendo a região de 18q11.2-q21.1.

MÉTODOS:
Relatamos dois novos pacientes e revisamos 27 casos adicionais nas bases de dados DECIPHER / ClinGen e quatro casos da literatura, com deleções mais proximais de 18q envolvendo deleção 18q11-q12 (somente banda 1; posição 17,2-43,5 Mb).

RESULTADOS:
Apresentações comuns de deleções 18q11-q12 incluem atraso no desenvolvimento / deficiência intelectual (DD / ID) (82%); atraso na fala / autismo / déficit de atenção e hiperatividade / outros problemas comportamentais (30%); defeitos cardíacos conotruncais (15%); e dismorfismo facial sutil / inespecífico. A deleção em quatro de cinco casos com defeito cardíaco foi distal ao GATA6, sugerindo um mecanismo alternativo que não a haploinsuficiência do GATA6 como uma causa subjacente de malformações cardíacas. A puberdade precoce com idade esquelética avançada foi observada pela primeira vez em um paciente, sugerindo um fenótipo único e expandido de deleção 18q proximal. Ao comparar as correlações genótipo-fenótipo do presente estudo com relatos prévios, as regiões críticas para fenótipos selecionados da síndrome de deleção 18q11-q12 poderiam ser estreitadasabaixo como segue: 38.8-43.5 Mb para moderado a severo DD / ID, 19.6-24.4 Mb e 26.9-28.6 Mb para defeito de coração conotruncal.

CONCLUSÃO:
O delineamento clínico detalhado das deleções proximais de 18q identificadas neste estudo deve contribuir para uma melhor compreensão das correlações genótipo-fenótipo e melhor cuidado de longo prazo dos pacientes com essa síndrome rara .

Fonte: https://www.ncbi.nlm.nih.gov/pubmed/31390163

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Texto Original



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.
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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