[A novel homozygous variant in THSD1 causes non-immune hydrops fetalis in a premature infant]

Hydrops fetalis is the final stage of several conditions that lead to fluid accumulation in the fetal tissues and body cavities, which can be life-threatening. With the advances and greater access to genome sequencing technologies, the spectrum of monogenic causes of hydrops fetalis has been increasing.

To describe the case of an infant diagnosed with non-immune hydrops fetalis who presents a previously undescribed homozygous pathogenic variant in the THSD1 gene, expanding the genotypic spectrum of this entity.

A 31-week premature newborn with hydrops fetalis diagnosed at 19 weeks of gestation, who presented ascites, pleural effusion, bilateral hydrocele, and edema, without chromosomal abnormalities and negative TORCH study. After an emergency cesarean delivery, signs of hypotonia, bradycardia, and cyanosis were observed, with multiple complications such as chylothorax, intestinal perforation, patent ductus arteriosus, and capillary hemangiomas. On physical examination, there were downward and outward slanted palpebral fissures, a depressed nasal bridge, low-set auricles, a globular abdomen, bilateral hydrocele, and midline hemangiomas at the occipital, cervical, and lumbar levels. Whole-exome sequencing revealed a homozygous truncating variant in the THSD1 gene (c.1009delC:p.Gln337Argfs*73), not previously described in the literature.

Reporting new cases of recently described conditions helps to delimit the phenotype and prognosis of the entity. Although, given the scarcity of reported cases, it is not possible to perform a genotype-phenotype evaluation; these cases indicate that the patient is likely to have a favorable prognosis.