# Prenatal Molecular Diagnosis of COL2A1-Associated Stickler Syndrome: Genotype–Phenotype Correlation in a Resource-Limited Healthcare Setting

## TL;DR

This paper describes a prenatal diagnosis of Stickler syndrome using molecular testing in a resource-limited setting, showing how genetic confirmation helps manage the condition and guide family counseling.

## Contribution

The study demonstrates the clinical value of prenatal molecular diagnosis for Stickler syndrome in a setting with limited access to genetic testing.

## Key findings

- A prenatal case of Stickler syndrome was confirmed via a COL2A1 frameshift variant identified through next-generation sequencing.
- Early genetic confirmation enabled multidisciplinary perinatal management and targeted clinical surveillance.
- The case highlights the importance of integrating molecular diagnostics into routine prenatal care for rare genetic disorders.

## Abstract

Stickler syndrome is a monogenic connective tissue disorder primarily caused by pathogenic variants in collagen-related genes, most commonly COL2A1. Prenatal diagnosis remains challenging, particularly in healthcare systems with limited access to molecular genetic testing. We report a prenatal case of suspected craniofacial anomaly detected on second-trimester ultrasound. Fetal DNA obtained by amniocentesis underwent next-generation sequencing. Parental testing was performed to assess inheritance. It was confirmed that autosomal dominant Stickler syndrome type I (ORPHA:90653) was caused by a heterozygous pathogenic frameshift variant in COL2A1 (c.3137del) that was inherited from the mother and identified in the fetus. Micrognathia was identified during prenatal ultrasound, and postnatal evaluation revealed characteristics that were consistent with Pierre Robin sequence and connective tissue involvement. The molecular discoveries elucidated the observed phenotype and facilitated multidisciplinary perinatal management. This case underscores the indispensable function of molecular diagnostics in the prenatal identification of monogenic disorders, including Stickler syndrome, in cases where conventional karyotyping is inadequate. Targeted clinical surveillance and family counseling are facilitated by early genetic confirmation. The report also emphasizes the necessity of incorporating molecular diagnostics into routine prenatal care for rare genetic diseases and the systemic limitations in access to genomic testing. Although the identified variant has been previously reported, this case highlights the clinical and diagnostic value of prenatal molecular confirmation in a resource-limited healthcare setting.