Nörogelişimsel Geriliği Olan ve Mikrodizin Analizinda Patojenik Kopya Sayısı Değişikliği Saptanan Çocukların Klinik Özellikleri

Year 2022, Volume: 22 Issue: 3, 151 - 158, 29.12.2022

Hülya Maraş Genç , Yasemin Kendir Demirkol , Hande Beklen Büşra Kutlubay , Ozlem Akgun-dogan , Gülhan Sözen

https://doi.org/10.26650/jchild.2022.1112958

Abstract

Amaç: Bu çalışmada, nörogelişimsel geriliği olan ve kromozomal mikrodizin analizinde patojenik kopya sayısı değişikliği saptanan çocukların klinik özelliklerini tanımlamayı amaçladık. Gereç ve Yöntem: Üçüncü basamak bir hastanenin pediatrik genetik ve pediatrik nöroloji polikliniğinde Ağustos 2017-Mart 2021 tarihleri arasında nörogelişimsel gecikme açısından değerlendirilen ve patojenik kopya sayısı değişikliği saptanan 0-18 yaş arası çocuklar retrospektif olarak analiz edildi. Bulgular: Çalışmaya 24 hasta dahil edildi, 15’i (%62,5) kızdı. Ortalama tanı yaşı 47.0±42.0 ay (yaş aralığı: 4-133 ay). Çocukların çoğunda (n=17, %70,8) iyi tanımlanmış OMIM mikrodelesyon/mikroduplikasyon sendromları saptandı. Yirmi dört hastada saptanan 28 kopya sayısı değişikliklerinin 21’i (%75) delesyon, 7’si (%25) duplikasyondu. On beş hastada (%62,5) global gelişme geriliği, 7 hastada (%29.2) zihinsel yetersizlik ve 3 hastada (%12.5) otizm spektrum bozukluğu vardı. Sırasıyla 4 ve 5 çocukta erken doğum öyküsü ve gestasyonel yaşa göre düşük doğum ağırlığı mevcuttu. Nörogörüntüleme 2 çocukta hipoksik-iskemik hasar ve 1 çocukta hipoglisemik sekel ile uyumluydu. Fasiyal dismorfizm 19 (%79.2), hipotoni 14 (%58.3), epilepsi 8 (%33,3), mikrosefali 7 (%29.2), makrosefali 2 (%8.3), görme bozukluğu 3 (%12,5) ve işitme kaybı 2 (%8,3) hastada saptandı. Sonuç: Kromozomal mikrodizin analizi, açıklanamayan nörogelişimsel gecikmesi olan hastalarda değerli bir tanısal araçtır. Perinatal asfiksi ve neonatal hipoglisemiye sekonder beyin hasarı olan çocuklarda bile, eşlik eden dismorfizm ve/veya multisistem tutulumu olan olgularda mikroarray analizi yapılmalıdır.

Keywords

Nörogelişimsel gerilik, zihinsel yetersizlik, global gelişme geriliği, otizm spektrum bozukuğu, kromozomal mikroarray, kopya sayısı değişikliği

Supporting Institution

yok

Clinical Characteristics of Children with Neurodevelopmental Delay and Pathogenic Copy Number Variations in Chromosomal Microarray Analysis

Abstract

Objective: In this study, we report the clinical characteristics of a small cohort of children with neurodevelopmental delay and pathogenic copy number variations (CNV) in chromosomal microarray. Materials and Methods: We retrospectively analyzed children aged 0-18 years with neurodevelopmental delay and a pathogenic CNV in the chromosomal microarray analysis, who had been evaluated in the pediatric genetics and pediatric neurology outpatient clinics of a tertiary hospital between August 2017 and March 2021. Results: Twenty-four patients were included, 15 (62.5%) of them were girls. The mean age at diagnosis was 47.0±42.0 months (age range: 4-133 months). Most of the children (n=17, 70.8%) were diagnosed with welldefined microdeletion/microduplication syndromes. Of 28 CNVs in 24 patients; 21 (75%) were deletions, 7 (25%) were duplications. Fifteen (62.5%) of them had GDD, seven (29.2%) had ID, and three (12.5%) had ASD. A history of preterm birth and small birth weight for gestational age were present in four and five children, respectively. Neuroimaging was compatible with hypoxic-ischemic injury in two children and hypoglycemic sequel in one child. Facial dysmorphism was present in 19 (79.2%), hypotonicity in 14 (58.3%), epilepsy in eight (33.3%), microcephaly in seven (29.2%), macrocephaly in two (8.3%), hearing impairment in two (8.3%), and visual impairment in three (12.5%) children. Conclusion: Chromosomal microarray analysis is a valuable tool in patients with unexplained neurodevelopmental delay. Even in children with brain injury secondary to perinatal asphyxia and neonatal hypoglycemia, microarray analysis should be performed in cases with concomitant dysmorphism and/or multisystem involvement.

Keywords

Nerodevelopmental delay, cognitive impairment, global developmental delay, autism spectrum disorder, chromosomal microarray, copy number variations

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