The Impact of Paternal Age on RASopathies: A Clinical Case Series Baba Yaşının RASopatiler Üzerindeki Etkisi: Klinik Bir Olgu Serisi
Genel Tip Dergisi, cilt.36, sa.2026, ss.1-4, 2026 (Scopus, TRDizin)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 36 Sayı: 2026
- Basım Tarihi: 2026
- Doi Numarası: 10.54005/geneltip.1771492
- Dergi Adı: Genel Tip Dergisi
- Derginin Tarandığı İndeksler: Scopus, Directory of Open Access Journals, TR DİZİN (ULAKBİM), Academic Search Ultimate (EBSCO)
- Sayfa Sayıları: ss.1-4
- Anahtar Kelimeler: De Novo variants, genetic counseling, paternal age effect, RASopathies
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Aim: RASopathies are a group of genetic disorders caused by germline variants in genes involved in the RAS/MAPK signaling pathway. These syndromes, including Noonan, Costello, and cardiofaciocutaneous (CFC) syndromes, which are typically inherited in an autosomal dominant manner but often occur sporadically due to de novo variants. This study aims to reassess our single-center case series with a clearer framing of the paternal age effect (PAE), strengthen interpretability, and highlight practical clinical implications. Methods: We retrospectively reviewed 25 clinically and molecularly confirmed RASopathy cases diagnosed at Ümraniye Training and Research Hospital (2018-2022). Six patients with parentally inherited variants were excluded, leaving 19 cases with de novo variants for analysis. For each proband, we documented the causal gene/variant, inheritance, and paternal age at conception. Analyses are descriptive; no control cohort was available. Results: Variants were most frequently identified in SOS1 (36.8%) and PTPN11 (26.3%). All 19 patients harbored de novo variants, and two variants (in RAF1 and NF1) were classified as novel. Paternal ages ranged from 25 to 43 years, with a mean of 34.0 years and a median of 33 years. Nine fathers (47.4%) were aged ≥35 years, consistent with the commonly accepted threshold for advanced paternal age. Conclusions: This series is consistent with a paternal age effect in RAS/MAPK–activating disorders. Given the modest sample and lack of controls, causal inference is limited. We outline practical counseling points and a prospective design to validate PAE magnitude in our setting.