Objective: Trisomy 21 remains the most common live-born aneuploidy and a major contributor to perinatal morbidity. Although prenatal screening, particularly non-invasive prenatal testing (NIPT), has advanced substantially, clinical management offers no corrective options. Emerging allele-specific genome-editing approaches propose targeted removal or silencing of the extra chromosome 21. This review summarizes current evidence and evaluates the translational relevance of these technologies in perinatal medicine.
Methods: A narrative review was conducted following PRISMA-aligned procedures. A structured search of PubMed, Scopus, and Web of Science (January 2000–July 2025) identified 1,242 records. After duplicate removal, title/abstract screening, and full-text assessment based on predefined inclusion criteria, 54 studies met eligibility requirements. Data were synthesized across four domains: mechanistic strategies, developmental applicability, translational feasibility, and ethical–regulatory considerations.
Results: Allele-specific CRISPR-Cas9 studies demonstrated selective cleavage of the supernumerary chromosome 21 in cellular models, with partial restoration of near-euploid transcriptional patterns. Additional approaches—XIST-mediated silencing and centromere destabilization—provided alternative mechanisms with varying stability and specificity. Evidence remains limited to in vitro systems, with no validated embryo or fetal applications. Key challenges include mosaicism, delivery barriers, individualized SNP targeting, and ethical governance.
Conclusions: Allele-specific chromosome editing represents a promising but still experimental direction for future perinatal therapeutics. Current findings justify continued multidisciplinary investigation while emphasizing cautious interpretation and rigorous ethical oversight prior to any clinical translation.

Abstrak
Tujuan: Trisomi 21 tetap menjadi aneuploidi yang paling sering ditemukan pada kelahiran hidup dan merupakan kontributor utama terhadap morbiditas perinatal. Meskipun skrining prenatal—khususnya non-invasive prenatal testing (NIPT)—telah mengalami kemajuan yang signifikan, penatalaksanaan klinis hingga kini belum menawarkan opsi korektif. Pendekatan pengeditan genom spesifik alel yang mulai berkembang mengusulkan penghilangan atau penghambatan terarah terhadap salinan ekstra kromosom 21. Tinjauan ini merangkum bukti terkini serta mengevaluasi relevansi translasional teknologi tersebut dalam kedokteran perinatal.
Metode: Tinjauan naratif dilakukan dengan mengikuti prosedur yang selaras dengan PRISMA. Pencarian terstruktur terhadap PubMed, Scopus, dan Web of Science (Januari 2000–Juli 2025) mengidentifikasi 1.242 rekaman. Setelah penghapusan duplikasi, penyaringan judul/abstrak, dan penilaian teks lengkap berdasarkan kriteria inklusi yang telah ditentukan, sebanyak 54 studi memenuhi persyaratan kelayakan. Data disintesis ke dalam empat domain: strategi mekanistik, aplikabilitas perkembangan, kelayakan translasional, serta pertimbangan etika dan regulasi.
Hasil: Studi CRISPR-Cas9 spesifik alel menunjukkan pemotongan selektif terhadap kromosom 21 supernumerari pada model seluler, dengan pemulihan parsial pola transkripsi menuju profil ekspresi gen yang menyerupai kondisi euploid. Pendekatan lain—seperti penghambatan berbasis XIST dan destabilisasi sentromer—menyediakan mekanisme alternatif dengan tingkat kestabilan dan spesifisitas yang bervariasi. Bukti saat ini terbatas pada sistem in vitro, tanpa aplikasi yang tervalidasi pada embrio maupun janin. Tantangan utama meliputi mosaikisme, hambatan pengantaran, kebutuhan penargetan SNP individual, serta tata kelola etis.
Kesimpulan: Pengeditan kromosom spesifik alel merupakan arah yang menjanjikan, namun masih bersifat eksperimental bagi terapi perinatal di masa mendatang. Temuan saat ini mendukung keberlanjutan penelitian multidisipliner, sekaligus menekankan perlunya interpretasi yang hati-hati dan pengawasan etika yang ketat sebelum penerapannya dalam praktik klinis.

Kata Kunci: Bedah genom janin; CRISPR-Cas9; Penyuntingan gen perinatal; Terapi kromosom; Trisomi 21

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