Fetal hydrops caused by a novel pathogenic MECOM variant.

Area of Science:

• Genetics
• Developmental Biology
• Pathology

Background:

• Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 (RUSAT-2) is a rare genetic disorder.
• RUSAT-2 is typically associated with postnatal symptoms including bone marrow failure and skeletal anomalies.

Observation:

• A female fetus presented with hydrops and intrauterine demise at 20 weeks gestation.
• Post-mortem examination revealed hydrops, pallor, truncus arteriosus, and bilateral radioulnar synostosis.

Findings:

• Whole genome sequencing identified a novel de novo heterozygous pathogenic loss-of-function variant in the MECOM gene.
• This variant was linked to the diagnosis of RUSAT-2, expanding its known clinical spectrum.

Implications:

• This case demonstrates the importance of comprehensive post-mortem examination and broad genetic sequencing for diagnosing rare prenatal conditions.
• The findings suggest RUSAT-2 may present with a significant prenatal phenotype, including fetal hydrops and demise, which was previously unrecognized.