Prenatal Spectrum of COL2A1-Related Spondyloepiphyseal Dysplasia Congenita: A Review and Two Case Reports.

Abstract

OBJECTIVE: To review the published literature on prenatal findings of COL2A1-related SEDC, summarizing reported imaging and molecular variants, and to describe two additional prenatal cases evaluated at a tertiary referral center. METHOD: A narrative review with a systematic search strategy was conducted to analyze prenatal imaging findings, gestational age at detection, and molecular diagnoses in cases of COL2A1-related SEDC. Clinical and molecular description of two additional fetal cases with postnatal molecular confirmation were also included. RESULTS: Gestational age at initial detection ranged from 11 to 28 weeks. Five reported cases occurred in a familial setting, while two were initially considered sporadic. In several cases, complementary imaging modalities were required to better characterize vertebral and ossification defects. A clear genotype-phenotype correlation could not be reliably established; no specific molecular pattern reliably predicted the severity of prenatal imaging findings or perinatal outcomes. CONCLUSION: Our findings highlight the nonspecific nature of prenatal manifestations in COL2A1-related SEDC, which despite being largely consistent across cases do not allow for a specific diagnosis without molecular confirmation or a known family history. These challenges underscore the need for a comprehensive diagnostic strategy that integrates detailed imaging, molecular genetic testing, and close collaboration within a multidisciplinary team.