Cytogenomic assessment of the diagnosis of 93 patients with developmental delay and multiple congenital abnormalities: The Brazilian experience

Abstract

OBJECTIVE:The human genome contains several types of variations, such as copy number variations, that can generate specific clinical abnormalities. Different techniques are used to detect these changes, and obtaining an unequivocal diagnosis is important to understand the physiopathology of the diseases. The objective of this study was to assess the diagnostic capacity of multiplex ligation-dependent probe amplification and array techniques for etiologic diagnosis of syndromic patients.METHODS:We analyzed 93 patients with developmental delay and multiple congenital abnormalities using multiplex ligation-dependent probe amplifications and arrays.RESULTS:Multiplex ligation-dependent probe amplification using different kits revealed several changes in approximately 33.3% of patients. The use of arrays with different platforms showed an approximately 53.75% detection rate for at least one pathogenic change and a 46.25% detection rate for patients with benign changes. A concomitant assessment of the two techniques showed an approximately 97.8% rate of concordance, although the results were not the same in all cases. In contrast with the array results, the MLPA technique detected ∼70.6% of pathogenic changes.CONCLUSION:The obtained results corroborated data reported in the literature, but the overall detection rate was higher than the rates previously reported, due in part to the criteria used to select patients. Although arrays are the most efficient tool for diagnosis, they are not always suitable as a first-line diagnostic approach because of their high cost for large-scale use in developing countries. Thus, clinical and laboratory interactions with skilled technicians are required to target patients for the most effective and beneficial molecular diagnosis.

Phenotype comparison among individuals with developmental delay/intellectual disability with or without genomic imbalances

“…; Zanardo et al . ). However, none of them compared the clinical features among individuals with or without GIs.…”

“…In South America, very few studies performing CMA in individuals with DD/ID exist (Krepischi-Santos et al 2006;Lay-Son et al 2015;Vianna et al 2016;Zanardo et al 2017). However, none of them compared the clinical features among individuals with or without GIs.…”

“…), owing to high costs for large‐scale application (Zanardo et al . ). Therefore, it would be interesting to establish clinical criteria that could indicate the individuals with a higher probability of presenting a GI and a conclusive diagnosis through CMA.…”

“…However, even considering the higher diagnostic yield of CMA, this technique is not widely performed for clinical diagnostic purposes in children with DD/ID in several countries (Lee et al 2018), owing to high costs for large-scale application (Zanardo et al 2017). Therefore, it would be interesting to establish clinical criteria that could indicate the individuals with a higher probability of presenting a GI and a conclusive diagnosis through CMA.…”

Epidemiologia das Síndromes Cromossômicas no Estado do Piauí: Relato dos primeiros 100 exames de cariótipos realizados no Estado

“…Em humanos estas alterações, cujas causas estão associadas a uma variedade de fatores etiológicos, podem ser detectadas em qualquer estágio de desenvolvimento do pré ao pós natal (Francine et al, 2014;Hennekam et al, 2013;Mendes et al, 2018;Verma, 2021) . No Brasil, entre 5 e 7% dos nascidos vivos apresentam alguma AC, enquanto as AC graves são estimadas em 57,2 por 1.000 nascidos vivos (de Souza et al, 2019;Junior et al, 2017;Paz et al, 2010;Reis et al, 2014;Silva et al, 2018;Teixeira et al, 2020;Verma, 2021;Zanardo et al, 2017). Esses dados, entretanto, pode estar subestimado, pois à medida que há uma melhora nos indicadores de saúde da população, as doenças genéticas e as AC tornam-se responsáveis por uma proporção crescente da mortalidade infantil (Melo, et al, n.d.;Pelaio & Kowalski, 2021).…”