SRSF1 haploinsufficiency in 17q22 deletion syndrome explains nuchal pellucida thickening and neurodevelopmental outcomes.

The study examined a cohort of 25 individuals, comprising one fetus presenting with nuchal pellucida thickening and 24 postnatal cases with 17q22 deletions. The primary objective was to identify the genetic etiology of nuchal pellucida thickening and characterize the associated neurodevelopmental phenotype. Whole-exome sequencing confirmed the specific variant arr[GRCh37] 17q22(55,501,204_56,476,808) x 1 as a de novo event in the fetal case, establishing SRSF1 haploinsufficiency as the driver of the condition.

In the 24 postnatal cases, consistent neurological abnormalities were observed across the entire cohort. Secondary outcomes included craniofacial features, neurological abnormalities, visual impairment, and intellectual disability. The findings suggest that SRSF1 haploinsufficiency is the fundamental genetic cause underlying the observed fetal ultrasound abnormalities and the subsequent neurodevelopmental phenotype.

Safety data, including adverse events, serious adverse events, and tolerability, were not reported in this review. The study design did not include a comparator group, and follow-up duration was not reported. These limitations restrict the ability to draw broad causal conclusions or assess long-term outcomes beyond the immediate phenotypic presentation.

This evidence provides an essential reference for prenatal genetic counseling and phenotypic interpretation of 17q22 deletion syndrome. Clinicians should recognize SRSF1 haploinsufficiency as a key factor when evaluating fetal ultrasound findings, while acknowledging the observational nature of the data and the small sample size.