Sources of Phenotypical Variability in Autism Spectrum Disorder and Their Effects on Treatment

Yıl 2026, Cilt: 18 Sayı: 2, 438 - 451

Gökçe Koçak , Dilara Özdemir , Asya Afacan , Buse Akıncı , Yasemin İmrek , Ali Evren Tufan

https://doi.org/10.18863/pgy.1634506

Öz

Autism Spectrum Disorder (ASD) is a clinically and etiologically heterogeneous neurodevelopmental disorder. Approaching ASD as a single categorical diagnosis without addressing heterogeneity may limit intervention efficacy. A narrative, critical review was conducted using the PubMed database for studies between 2020-2025 and using “autism” AND “heterogeneity” (n= 3869) and “ASD” AND “heterogeneity” (n= 2391). A total of 435 references were selected based on titles, 167 based on abstracts, and 89 based on text reviews. Finally, 59 studies were reviewed. The DSM-5 criteria and their evolution, genetics, gender, environmental/epigenetic risk factors, comorbidities, development, syndromic vs. non-syndromic presentations, simplex vs. multiplex families, and autistic regression were the main sources of heterogeneity in the studies. The “deficit” term in the DSM-5 should be operationalized in conjunction with disability levels. ASD should be better characterized in female samples. Studies on genetic, environmental, and epigenetic risk factors should model these interactions. Protective factors should also be evaluated in future studies. Comorbidities may be grouped according to type (psychiatric vs. medical) and degree (symptom vs. syndrome), and temporal changes in symptoms can be modelled. Incident ASD cases should be screened using genetic tests and evaluated for dysmorphology. International databases of simplex/multiplex families and regressive ASD cases may help better characterize samples.

Anahtar Kelimeler

ASD , autism , phenotype , genetics , developmental regression , multiplex

Otı̇zm Spektrum Bozukluğunda Fenotipik Değı̇şkenliğin Kaynakları ve Tedavi Üzerindeki Etkileri

Öz

Otizm Spektrum Bozukluğu (OSB) klinik ve etiyolojik olarak heterojen bir nörogelişimsel bozukluktur. Heterojenliği ele almadan OSB'ye tek bir kategorik tanı olarak yaklaşmak, müdahalelerin etkilerini sınırlayabilir. 2020-2025 yılları arasındaki çalışmalar için PubMed veri tabanı kullanılarak ve “autism” AND “heterogeneity” (n= 3869) ve “autism spectrum disorder” AND “heterogeneity” (n= 2391) kullanılarak anlatısal, eleştirel bir inceleme yapılmıştır. Toplam 435 referans başlıklara göre, 167'si özetlere göre ve 89'u metinler gözden geçirilerek seçilmiştir. Son olarak, 59 çalışma gözden geçirilmiştir. DSM-5 kriterleri ve bunların değişimi, genetik, cinsiyet, çevresel/epigenetik risk faktörleri, komorbiditeler, gelişim, sendromik ve sendromik olmayan sunumlar, simpleks ve multipleks aileler ve otistik regresyon heterojenliğin ana kaynaklarıydı. DSM-5'teki “eksiklik” terimi, engellilik düzeyleri ile birlikte operasyonel hale getirilmelidir. OSB kadın örneklemler arasında daha iyi karakterize edilmelidir. Genetik, çevresel ve epigenetik risk faktörleri üzerine yapılan çalışmalar, bunların etkileşimlerini modellemelidir. Koruyucu faktörler de değerlendirilmelidir. Komorbiditeler türlerine (psikiyatrik ve tıbbi) ve derecelerine (semptom ve sendrom) göre gruplandırılabilir ve semptomlardaki zamansal değişiklikler modellenebilir. OSB vakaları genetik testlerle taranmalı ve dismorfoloji açısından değerlendirilmelidir. Simpleks/ multipleks ailelerin ve gerileyen OSB vakalarının uluslararası veri tabanları, örneklerin daha iyi karakterize edilmesine yardımcı olabilir.

Anahtar Kelimeler

ASD , autism , phenotype , genetics , developmental regression , multiplex

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