Pediatrik Nörolojide Klinik Fenotipler ve Kromozomal Mikrodelesyon/Duplikasyonlar Arasındaki İlişki

Year 2021, Volume: 23 Issue: 1, 97 - 109, 30.04.2021

Sevim Türay , Recep Eröz , Esra Habiloğlu Nadide Melike Sav

https://doi.org/10.18678/dtfd.881659

Cited By: 1

Abstract

Amaç: Bu çalışmanın amacı, günlük pediatrik nöroloji pratiğinde kromozomal mikrodizi analizinin (chromosomal microarray analysis, CMA) tanısal kullanışlılığını saptamak ve bu testi gerektiren hastalar için kılavuz olan klinik parametreler belirlemektir.
Gereç ve Yöntemler: Pediatrik nöroloji kliniğimize 2018 ve 2020 yılları arasında çeşitli nedenlerle başvuran global gelişme geriliği/zihinsel yetersizlik (global developmental delay/intellectual disability, GDD/ID) olan 91 hastanın CMA sonuçları incelendi. CMA’da del/dup tespit edilen 34 (%37,4) hastanın ve normal CMA’ya sahip olan 57 (%62,6) hastanın demografik ve klinik verileri karşılaştırıldı.
Bulgular: İki grup arasında yaş, cinsiyet, doğum şekli, doğum zamanı gibi demografik özellikler bakımından istatistiksel olarak anlamlı bir farklılık yoktu. Dismorfizm, hipotoni ve miyelinizasyon anormallikleri CMA’da del/dup olan hastalarda normal CMA’lı hastalara göre önemli ölçüde daha sıktı. Normal CMA grubunda makrosefali ve obezite sıklığı daha yüksekti ve bu grupta epileptik hastalardaki generalize konvulsiyon sıklığı daha yüksekti. Analizde del/dup saptanan 34 vakadan 19'u (%55,9) patojenik, 15'i (%44,1) klinik önemi bilinmeyen (muhtemelen patojenik, muhtemelen iyi huylu ve sınıflandırılamayan) olarak kabul edildi.
Sonuç: CMA pahalı, zahmetli ve zaman alan bir test olduğundan, CMA talep edilirken klinik parametrelerin dikkate alınması yüksek tanısal verimlilik sağlayacaktır. Dismorfizm, hipotoni ve miyelinizasyon gecikmesi olan GDD/ID hastalarında kopya sayısı değişiklikleri yüksek olasılıkla saptanabilir. Bu hastalarda farklı bir etyoloji düşündüren herhangi bir bulgunun olmadığı durumlarda, CMA pediatrik nöroloji pratiğinde tercih edilebilir bir genetik analizdir.

Keywords

Kromozomal mikrodizi analizi;, pediatrik nöroloji;, miyelinizasyon geriliği;, hipotoni;, global gelişme geriliği;, zihinsel yetersizlik

The Relationship Between Clinical Phenotypes and Chromosomal Microdeletions/Duplications in Pediatric Neurology

Abstract

Aim: The aim of this study was to determine the diagnostic utility of chromosomal microarray analysis (CMA) in daily pediatric neurology practice and to identify the guiding clinical parameters for patients requiring this test.
Material and Methods: The CMA results for 91 patients with global developmental delay/intellectual disability (GDD/ID) admitted to our pediatric neurology clinic for various reasons between 2018 and 2020 were examined. Demographical and clinical data for 34 patients (37.4%) in whom del/dup was determined at CMA and 57 patients (62.6%) with normal CMA were compared.
Results: There was no statistically significant difference between two groups in terms of demographic characteristics such as age, gender, type of delivery, gestational age, etc. Dysmorphisms, hypotonia, myelination abnormalities were significantly more frequent in patients with del/dup than in patients with normal result. The frequency of macrocephaly and obesity was higher in the normal group, and that of generalized seizures was higher among epileptic patients in this group. Nineteen (55.9%) of the 34 cases who have del/dup detected at analysis were regarded as pathogenic, 15 (44.1%) as uncertain clinical significance (likely pathogenic, likely benign and no subclassification).
Conclusion: Since CMA is an expensive, laborious, and time-consuming test, considering clinical parameters when requesting CMA will yield high diagnostic efficiency. A high possibility of copy number variants may be predicted in GDD/ID patients with dysmorphisms, hypotonia, and myelination delay. CMA should represent the genetic analysis of choice in pediatric neurology practice in case of no finding suggesting a different etiology in these patients.

Keywords

Chromosomal microarray analysis;, pediatric neurology;, myelination delay;, hypotonia;, global developmental delay;, intellectual disability

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