Gelişim Geriliği/Entellektüel Yetersizliği Olan Çocuklarda Etiyolojiye Yönelik Genetik Testlerin Planlama ve Değerlendirmesinde Güncel Durum: Tek Merkez Deneyimi

Öz

Giriş ve Amaç: Gelişim geriliği (GG) ve entelektüel yetersizlik (EY) fenotipik ve genetik olarak heterojen bir grup hastalıktır. GG/EY olguların etiyolojisinde altta yatan önemli bir kısmını genetik nedenler oluşturmaktadır. Bu araştırmadaki amacımız, GG/EY tanısı olan olguların genetik tanılama oranlarına ilişkin verilerin araştırılmasıydı. Gereç ve Yöntemler: GG/EY ön tanısıyla Ocak 2020 ile Aralık 2020 tarihleri arasında gelişim testlerine yönlendirilen 0-6 yaş arasında 578 olgunun hastane kayıtları retrospektif incelendi. Bu olgulara yönelik yapılan genetik testlerin sonuçları değerlendirmeye alındı. Bulgular: Yapılan gelişim testi sonucunda GG/EY saptanan olguların oranı %68,3 idi. GG/EY tanısı alan olguların içerisinde genetik polikliniğine başvuruda bulunan olguların oranı ise %7,4 idi. Uygulanan genetik testler sonucunda GG/EY ile ilişkili genetik varyant saptanma oranı %37,9 idi. Sonuç: Nörogelişimsel bozukluklarda genetik değerlendirme ve genetik testlere ulaşıma ilişkin kısıtlılıklar tüm dünyada önemli bir sorun olarak karşımıza çıkmaktadır. Çalışmamızda GG/EY olgularının genetiğe yönlendirme oranı ulaşılabilir birçok ülke verileri ile kıyaslandığında düşük olarak saptanmıştır. Ülkemizde GG/EY tanılı olgular için uygun genetik danışmanlığı sağlamak, prognozu belirleyebilmek ve gelecek nesillere yönelik birincil koruma sağlayabilmek için ülke genelinde uygulanabilecek sağlık politikalarına ihtiyaç duyulmaktadır.

Anahtar Kelimeler

• Gelişme geriliği
• Kromozomal Karyotipleme
• Kromozomal Mikroarray
• MECP2
• Tüm Ekzom Dizileme

Current Situation in Planning and Evaluation of Etiological Genetic Tests in Children with Developmental Delay/Intellectual Disability: Single Center Experience

Öz

Objective: Developmental delay (DD) and intellectual disability (ID) are a phenotypically and genetically heterogeneous group of diseases. Genetic causes constitute an important part of the underlying etiology of DD/ID cases. Our aim in this study was to investigate the data on the genetic diagnosis rates of cases with DD/ID. Materials and Methods: Hospital records of 578 cases aged 0-6 years, who were referred to developmental tests between January 2020 and December 2020 with a preliminary diagnosis of DD/EY, were retrospectively analyzed. The results of genetic tests for these cases were evaluated. Results: The rate of cases with DD/ID as a result of the developmental test was 68.3%. Among the cases diagnosed as DD/ID, the rate of the cases who applied to the genetic polyclinic was 7.4%. As a result of the applied genetic tests, the rate of detection of genetic variants associated with DD/ID was 37.9%. Conclusion: Restrictions on genetic evaluation and access to genetic tests in neurodevelopmental disorders are an important problem all over the world. In our study, the rate of referral to genetics of DD/ID cases was found to be low when compared to the data of many available countries. In our country, health policies that can be implemented throughout the country are needed in order to provide appropriate genetic counseling for cases diagnosed with DD/ID, to determine the prognosis, and to provide primary protection for future generations.

Anahtar Kelimeler

• Developmental delay
• Chromosomal Karyotyping
• Chromosomal Microarray
• MECP2
• Whole Exome Sequencing

Kaynakça

1. 1. Tassé, M.J, Luckasson, R, Nygren M, AAIDD proposed recommendations for ICD–11 and the condition previously known as mental retardation, Intellectual and developmental disabilities, 2013, 51(2), 127–31.
2. 2. Mukaddes, N.M, Ercan, E.S, Nörogelişimsel Bozukluklar; İstanbul, Nobel Tıp Kitabevi, 2018
3. 3. Thapar, A, Rutter, M, Neurodevelopmental disorders. Rutter’s child and adolescent psychiatry, 2015,31–40.
4. 4. Ismail, F.Y, Shapiro, B.K, What are neurodevelopmental disorders? Current opinion in neurology, 2019, 32(4), 611–616.
5. 5. Demirci, A, İzmir il merkezinde 3-60 ay arası çocuklarda gelişme geriliği prevalansı, 2015
6. 6. Tunçeli, H.İ, Zemmrat, R, Erken çocukluk döneminde gelişimin değerlendirilmesi ve önemi, Eğitim Kuram ve Uygulama Araştırmaları Dergisi, 2017, 3(3), 1–12.
7. 7. Demirci, A, Kartal, M, Çocukluk dönemine ait önemli bir sorun: Gelişme geriliği ve erken tanının önemi, The Journal of Turkish Family Physician, 2012, 3(4), 1–6.
8. 8. Richards, S, Aziz, N, Bale, S, Bick, D, Das, S, Gastier-Foster, J, Grody, W.W, Hegde, M, Lyon, E, Spector, E, Voelkerding, Rehm, H.L, Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, Genetics in medicine, 2015, 17(5), 405–423.

9. 9. Moeschler, J.B, Shevell, M, Saul, R.A, Chen, E, Freedenberg, D.L, Hamid, R, Jones, M.C, Stoler, J.M, MD; Tarini, B.A, Comprehensive evaluation of the child with intellectual disability or global developmental delays, Pediatrics, 2014, 134(3), e903–18.
10. 10. Muhle RA, Reed HE, Vo LC, Mehta S, McGuire K, Veenstra-VanderWeele J, Pedapati E, Clinical Diagnostic Genetic Testing for Individuals With Developmental Disorders, Journal of the American Academy of Child and Adolescent Psychiatry., 2017, 56(11), 910.
11. 11. Miller, D.T, Adam, M.P, Aradhya, S, Biesecker, L.G, Brothman, A.R, Carter, N.P, et al., Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies, The American Journal of Human Genetics, 2010, 86(5), 749–64.
12. 12. Srivastava, S, Love-Nichols, J.A, Dies, K.A, Ledbetter, D.H, Martin, C.L, Chung, W.K, Firth, Frazier, T, Hansen, R.L, Prock, L, Brunner, H, Hoang, N, Scherer, S.W, Sahin, M, Miller, D.T, NDD Exome Scoping Review Work Group, Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders. Genetics in Medicine, 2019, 21(11), 2413–21.
13. 13. Michelson, D.J, Shevell, M.I, Sherr, E.H, Moeschler, J.B, Gropman, A.L, Ashwal, S, Evidence report: Genetic and metabolic testing on children with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society, Neurology, 2011, 77(17), 1629–35.
14. 14. McGrew, S.G, Peters, B.R, Crittendon, J.A, Veenstra-VanderWeele, J, Diagnostic yield of chromosomal microarray analysis in an autism primary care practice: which guidelines to implement? Journal of autism and developmental disorders, 2012, 42(8), 1582–91.
15. 15. Roesser, J, Diagnostic yield of genetic testing in children diagnosed with autism spectrum disorders at a regional referral center, Clinical pediatrics, 2011, 50(9), 834–43.
16. 16. Savatt, J.M, Myers, S.M, Genetic testing in neurodevelopmental disorders, Frontiers in Pediatrics, 2021, 9, 52.
17. 17. Amiet, C, Couchon, E, Carr, K, Carayol, J, Cohen, D, Are there cultural differences in parental interest in early diagnosis and genetic risk assessment for autism spectrum disorder? Frontiers in pediatrics, 2014, 2, 32.
18. 18. Codina-Solà, M, Pérez-Jurado, L.A, Cuscó, I, Serra-Juhé, C. Provision of genetic services for autism and its impact on Spanish families. Journal of autism and developmental disorders, 2017, 47(10), 2947–56.