ARCN1 Related Syndrome: A Rare Case Report

Background: ARCN1-related syndrome is a rare genetic disorder with a wide phenotypic spectrum. The most commonly reported features include fetal and postnatal growth restriction, micrognathia, microcephaly, rhizomelic limb shortening, and preterm birth. The syndrome is caused by variants in the ARCN1 gene, which encodes the delta subunit of the coatomer protein complex I (COPI), a key component involved in intracellular protein transport between the Golgi apparatus and the endoplasmic reticulum. Case presentation: We report a prenatal case of a fetus presenting with severe fetal growth restriction, short long bones, and microcephaly, which was delivered preterm. Fetal whole-exome sequencing identified a novel de novo heterozygous variant in ARCN1 (c.1313T>C), which has not been previously reported in the literature or population databases. The observed prenatal and early postnatal phenotype was consistent with the spectrum of features described in ARCN1-related syndrome. Conclusion: This report represents the first case described in Greece and the first report of this specific ARCN1 variant. Our findings expand the prenatal phenotypic and molecular spectrum of ARCN1-related syndrome and highlight the importance of early molecular diagnosis for accurate prenatal counseling and pregnancy management.