Expanding the Phenotype of 8p23.1 Deletion Syndrome: Eight New Cases Resembling the Clinical Spectrum of 22q11.2 Microdeletion

• Published in: The Journal of pediatrics Vol. 252; pp. 56 - 60.e2
• Main Authors: Montenegro, Marília Moreira, Camilotti, Débora, Quaio, Caio Robledo D’Anglioli Costa, Gasparini, Yanca, Zanardo, Évelin Aline, Rangel-Santos, Andreia, Novo-Filho, Gil Monteiro, Francisco, Gleyson, Liro, Lucas, Nascimento, Amom, Chehimi, Samar Nasser, Soares, Diogo Cordeiro Queiroz, Krepischi, Ana C.V., Grassi, Marcília Sierro, Honjo, Rachel Sayuri, Palmeira, Patricia, Kim, Chong Ae, Carneiro-Sampaio, Magda Maria Sales, Rosenberg, Carla, Kulikowski, Leslie Domenici
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2023
• Subjects: Chromosome Deletion; DiGeorge Syndrome - diagnosis; DNA Copy Number Variations; Heart Defects, Congenital - diagnosis; Heart Defects, Congenital - genetics; Humans; Phenotype; 8p23.1DS; CNV; MLPA; VUS; CDH
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2022.08.051

To report the effectiveness of early molecular diagnosis in the clinical management of rare diseases, presenting 8 patients with 8p23.1DS who have clinical features that overlap the phenotypic spectrum of 22q11.2DS. This report is part of a previous study that aims to provide a precocious molecular diagnosis of the 22q11.2 deletion syndrome in 118 infants with congenital heart disease. To confirm the clinical diagnosis, patients underwent comparative genomic screening by the multiplex ligation-dependent probe amplification (MLPA) assay with the SALSA MLPA probemix kits P064-B2, P036-E1, P070-B2, P356-A1, and P250- B1. Subsequently, the patients performed the genomic microarray using the Infinium CytoSNP-850K BeadChip to confirm the deletion, determine the breakpoints of the deletion, and search for genomic copy number variations. MLPA performed with 3 different kits revealed the 8p23.1 typical deletion involving the PPP1R3B, MSRA, and GATA4 genes in the 5 patients. The array analysis was performed on these 5 patients and 3 other patients (8 patients) who also had clinical suspicion of 22q11 deletion (8 patients) allowed a precise definition of the breakpoints and excluded other genomic abnormalities. Cytogenomic screening was efficient in establishing a differential diagnosis and ruling out the presence of other concomitant syndromes. The clinical picture of the 8p23.1 deletion syndrome is challenging; however, cytogenomic tools can provide an exact diagnosis and help to clarify the genotype-phenotype complexity of these patients. Our reports underline the importance of early diagnosis and clinical follow-up of microdeletion syndromes.