Ayşegül KAYMAK, Rahmi DUMAN, Mehmet BALCI

Bir halk sağlığı problemi olan şaşılıkların mitokondriyal sitopatilerle birlikteliği

Şaşılık gözlerde kayma olarak bilinen sabit veya aralıklı olarak göz hareketlerinde sapma ve azalmış binoküler görme ile karakterize genellikle ambliyopi ile sonuçlanan heterojen bir grup hastalıktan oluşmaktadır. Şaşılığın değişik sınıflamaları mevcuttur. Manifest şaşılıkları; konkomitant ve inkomitant olarak ikiye ayırabiliriz. Konkomitant şaşılık; çocuklarda sık görülen, kayan gözün her bakış pozisyonunda fikse eden göze eşlik ettiği ve kayma açısının her bakış pozisyonunda aynı olduğu bir şaşılık formudur. İnkomitant şaşılık ise erişkinlerde sık görülen, kayma açısının her bakış pozisyonunda farklı olduğu, bir veya birden fazla göz kasının felcine bağlı olarak ortaya çıkan (paralitik) bir şaşılık formudur. Konkomitant şaşılığın genetiği karmaşık yapısından dolayı tam olarak aydınlatılamamıştır. İnkomitant form toplumda daha az görülmesine rağmen, genetiği konkomitant forma göre daha fazla aydınlatılabilmiştir. Mitokondriyal sitopatiler; anneden aktarılan mitokondriyal DNAnın (MtDNA) silinmesi veya mutasyonu sonucu oluşan ve adenozin trifosfat (ATP) üretiminin bozulmasına yol açan bir grup hastalıktan oluşmaktadır. Mitokondriyal sitopatilerde oluşan mutasyonlar sonucunda öncelikle kasların yoğun olduğu, oksidatif fosforilasyon ihtiyacının fazla olduğu organlar önemli derecede etkilenmektedir. Göz kapaklarından ekstraoküler kaslara, retinaya kadar tüm görme sistemi yüksek oksidatif fosforilasyona ihtiyaç duymaktadır. Bu yüzden göz ilk etkilenen organlardan birisidir. Mitokondriyal sitopatilerde en sık gözlenen bulgular ise şaşılık ve pitozistir. Mitokondriyal DNA mutasyonları ve silinmeleri sonucu oluşan özel şaşılık tipleri ise kronik progressif eksternal oftalmopleji (KPEO) ve Kearns-Sayre Sendromu (KSS)dur. Şaşılıkta genetiğin rolünün aydınlatılması hastalık patogenezinin daha iyi anlaşılmasına ve daha etkin tedavi protokolleri geliştirilmesine basamak olacaktır. Mevcut tedavi yöntemleri ile tedavide yetersiz kaldığımız olguları daha sıkı takip etmemizi ve farklı tedavi yöntemleri geliştirmemizi sağlayacaktır. Bu derlemede; klinikte çok kolay birbirine karışabilecek olan inkomitant şaşılıkların bir bölümünü oluşturan mitokondriyal sitopatilerle birlikte görülen şaşılıkların klinik ve genetik özelliklerini ortaya koymayı amaçladık.

The association of strabismus- a public health problem- with mitochondrial cythopathies

Hospital, Department Of Medical Genetics, AnkaraStrabismus which is known as misalignment of eyes, is characterized with stable or intermittent aberrance of eye movements along with reduced binocular vision and it is composed of a heterogeneous group of diseases which are generally concluded with ambliyopia. There are variable classifications of strabismus. We can separate manifest strabismus into two, as concomitant and incomitant. Concomitant strabismus which is often observed in children is a form of strabismus, in which squinting eye accompanies with fixed eye in every view position and the angle of eye shearing is identical in every view position. Whereas, incomitant strabismus is frequently observed in adults, the angle of eye shearing is different in every view position and it is a paralytic form of strabismus which occurs due to the paralysis of one or more of the eye muscles. The genetics of the concomitant strabismus is not precisely enlightened because of its complicated structure. Although, incomitant form of strabismus is observed in lesser extent in the general population; its genetics are enlightened more compared to the concomitant form of strabismus. Mitochondrial cytopathies are composed of a group of diseases that occur as the result of deletion or mutation of maternally transmitted mitochondrial DNA (MtDNA) and this group of disorders causes the disruption of ATP (adenosine triphosphate) production. In the result of mutations that have occurred in the mitochondrial cytopathies; at the first place are organs which contain high proportion of muscle and have excessive oxidative phosphorylation requirement, are affected significantly. All visual system, from eyelids to extraocular muscles and retina, needs excessive oxidative phosphorylation. For this reason, the eye is one of the organs that is affected primarily. Most frequently observed findings in mitochondrial cytopathies are strabismus and ptosis. Specific strabismus types that are formed in the result of mitochondrial DNA mutations and deletions are Chronic Progressive External Ophthalmoplegia (CPEO) and Kearns-Sayre Syndrome (KSS). The enlightening of the role of genetics on strabismus is going to be a step toward better understanding of disease pathogenesis and for creating more effective treatment protocols. Additionally, this will provide us to develop distinct treatment methods; and to follow-up cases more tightly, which are not treated efficiently with existing treatment methods. In this review, we purposed to compile the clinical and genetic features of strabismus that is observed with mitochondrial cytopathies, which constitute the one part of incomitant strabismuses that can be very easily intermingled with each other.

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