Filiz HAZAN, Semra GÜRSOY, Aycan ÜNALP, Ünsal YILMAZ

Klasik Rett Sendromu Olan Hastaların Klinik Değerlendirmesi ve MECP2 gen Analizi

GİRİŞ ve AMAÇ: Bu retrospektif çalışma, genetik tanı almış klasik Rett Sendromu (RTT) hastalarında, klinik bulguları değerlendirmeyi amaçlamaktadır. YÖNTEM ve GEREÇLER: 2010-2020 yılları arasında, genetik polikliniğinde RTT tanısı almış 16 hasta, sendromun tanı kriterlerine göre değerlendirildi. Pyrosekans, sanger sekans ve multipleks ligasyona bağlı prob amplifikasyonu analiz sonuçları incelendi. BULGULAR: Klasik RTT tanısı için gerekli olan 4 ana kritere ek olarak, hastalarda en sık saptanan bulgular; diurnal bruksizm (16/16; %100), epilepsi (11/16; %68,7) ve mikrosefali (11/16; %68,7) idi. Erken başlangıçlı epilepsi, 6 hastada saptandı (6/11; %54,5). Bu hastaların dördünde, ilaca dirençli epilepsi vardı. Geç başlangıçlı epilepsisi olan 5 hastanın 4’ü antikonvülsan tedaviye iyi yanıt verdi. Skolyoz, nefes alma problemleri, periferik vazomotor bozukluk ve uyku problemleri sırasıyla %37,5; %18,7; %25 ve %12,5 sıklıkta saptandı. 16 hastada, toplam 9 farklı MECP2 gen varyantı tanımlandı. Nonsense varyant, ensık varyant tipiydi (7/16 hasta; %43,7). Çalışmada saptanan varyantlar; p.Arg168Ter (n =5); p.Thr158Met (n = 2); p.Arg255Ter (n = 2); p.Arg106Trp (n = 1); p.Arg270GlufsTer19 (n = 1); p.Lys286ProfsTer2 (n = 1); p.Leu386_Thr400delinsPro (n = 1); Exon 4 del (n = 2) ve Exon 3-4 del (n = 1) idi. TARTIŞMA ve SONUÇ: p.Arg168Ter, patojenik varyantı, Türk klasik RTT hastalarında yaygındır. Diurnal bruksizm, mikrosefali ve epilepsi, bu sendromun sık bulgularındandır. Klasik RTT'li hastaların yarısından fazlasında epilepsi gelişir ve özellikle erken başlangıçlı epilepsi, hastaların önemli bir kısmında ilaca dirençli olma eğilimindedir.

Anahtar Kelimeler:

Rett Sendromu, MECP2 geni, epilepsi, Diurnal bruksizm, mikrosefali, ilaç direnci

Clinical Evaluation of Patients with Classical Rett Syndrome and MECP2 Gene Analysis

INTRODUCTION: This retrospective study aims to evaluate the clinical manifestations in genetically confirmed classical Rett syndrome (RTT) patients. METHODS: Sixteen patients clinically diagnosed with classical RTT between 2010 and 2020 were evaluated according to diagnostic criteria for this syndrome. The results of pyrosequencing, sanger sequencing, and multiplex ligation-dependent probe amplification of MECP2 gene were inspected. RESULTS: Besides the 4 main criteria of RTT which are necessery for the diagnosis of classical RTT, diurnal bruxism (16/16 patients), epilepsy (11/16; 68.7%) and microcephaly (11/16; 68.7%) were the most common features in the patients. Early onset epilepsy was detected in six patients (6/11; 54.5%). Four of them had drug-resistant epilepsy. Four out of 5 patients with late onset epilepsy had a good response to the anticonvulsant treatment. Scoliosis, breathing problems, peripheral vasomotor disturbances and sleep problems were detected in 37.5%, 18.7%, 25% and 12.5% of the patients, respectively. A total of 9 different MECP2 gene variants were identified in the 16 patients. Nonsense variant was the most common variant type (7/16; 43.7%). The detected variants were p.Arg168Ter (n =5); p.T158M (n = 2); p.R255X (n = 2); p.Arg106Trp (n = 1); p.Arg270GlufsTer19 (n = 1); p.Lys286ProfsTer2 (n = 1); p.Leu386_Thr400delinsPro (n = 1); Exon 4 del (n = 2) and Exon 3-4 del (n = 1). DISCUSSION AND CONCLUSION: The p.Arg168Ter variant is common in classical RTT patients in Turkey. diurnal bruxism, microcephaly and epilepsy are common features in this syndrome. Epilepsy develops in more than half of patients with classical RTT and especially early-onset epilepsy tends to be drug resistant in a substantial proportion of the patients.

Keywords:

Rett Syndrome MECP2 gene, epilepsy, diurnal bruxism, diurnal bruxism, microcephaly, drug resistant,

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