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Öz

Autism affects approximately 1/100 people. The main problems in this disease, in which genetic factors play important causative roles appear in areas of social interactions, language acquisition and communication skills. Stereotypical movements and serious limitation in interests are seen in the majority of patients. Intellectual deficiency seen in 75% of the patients requires life-long social and educational support, therefore causes a serious health concern. Data obtained from research studies for delineating autism etiology revealed significant correlations between autism and some cytogenetic aberrations in almost every chromosome. Recent technical advances in molecular genetics facilitated evaluations in a finer level and thus caused the identification of significant associations between autism and genomic copy number variations. In addition to some chromosomal abnormalities revealed via conventional cytogenetic analyses and various copy number variations detected through molecular methods, many genetic syndromes caused by single gene mutations have autism signs. Delineation of etiopathogenesis has major implications in the planning of a treatment strategy and genetic counseling related with disease course and recurrence risk. Cytogenetic and molecular tests for autism diagnosis must be performed according to the results of algorithms formed with genetic details and genetic abnormalities and syndromes related with autism must be ruled out in differential diagnosis. Thus, the prevention of potential complications and the onset of appropriate therapy can be possible. Conclusively, medical management of autistic patients must be handled by a team approach and this team must consist of clinicians appropriate for the patient’s age, psychologist/pedagogue, physiotherapist, speech therapist and a medical geneticist.

Anahtar Kelimeler

• Autistic spectrum disorders; autism; genetics

OTİZM ETYOLOJİSİNDE GENETİK VE GÜNCEL PERSPEKTİF

Öz

Otizm yaklaşık yüz kişiden birini etkilemektedir. Oluşum nedenleri arasında genetik etmenlerin önemli rol oynadığı bu hastalıktaki temel problemler, sosyal ilişkiler, dil gelişimi ve iletişim becerilerinde kendini göstermektedir. Hastaların büyük kısmında tekrarlayıcı hareketler ve ilgi alanlarında ciddi kısıtlılık söz konusudur. Otizmli hastaların %75’inde gözlenen entellektüel yetersizlik, yaşam boyu önemli düzeyde sosyal ve eğitsel desteğe gereksinim yarattığından ciddi bir toplumsal sağlık problemi oluşturmaktadır. Otizm etyolojisinin aydınlatılmasına yönelik çalışmalardan elde edilen verilerde, hemen hemen tüm kromozomlarda gözlenen bazı sitogenetik düzensizlikler ile otizm arasında anlamlı bağlantılar bulunduğu gösterilmiştir. Son yıllarda moleküler genetikte yaşanan teknolojik ilerlemeler daha ince düzeyde değerlendirmeler yapılmasına olanak sağlamış ve bununla birlikte genomdaki çeşitli kopya sayısı değişikliklerinin otizmle önemli ilişkisi bulunduğu belirlenmiştir. Konvansiyonel sitogenetik analizlerle belirlenebilen bazı kromozom anomalileri, moleküler yöntemlerle gözlenebilen çeşitli kopya sayısı değişikliklerinin otizmle ilişkilendirilmesinin yanısıra tek gen mutasyonlarının neden olduğu genetik sendromların çoğunda da otizm belirtileri bulunmaktadır. Etyopatogenezin aydınlatılması uygun tedavinin planlanması, hastalığın seyri ve tekrarlama riskiyle ilişkili genetik danışma verilmesi açısından büyük önem taşımaktadır. Otizm tanısında kullanılacak sitogenetik ve moleküler testler genetik ayrıntılardan oluşturulmuş belli algoritmaların sonucuna göre uygulanmalı, ayırıcı tanıda genetik düzensizlikler ve otizmle ilişkili sendromlar belirlenmelidir. Böylece hem potansiyel komplikasyonların önüne geçmek, hem de uygun tedavinin başlatılması mümkün olabilir. Sonuç olarak, otizm hastalarına tıbbi yaklaşım bir ekip tarafından yapılmalı ve bu ekibin içinde hasta yaş gurubuna uygun klinisyen, psikolog/pedagog, fizyoterapist, konuşma terapistinin yanısıra tıbbi genetik uzmanları bulunmalıdır.

Anahtar Kelimeler

• Otizm spektrum bozuklukları, otizm, genetik

Kaynakça

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