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Smith-Lemli-Opitz Syndrome

New syndrome mimicking SLOS potentially linked to prenatal fentanyl exposure

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A recent study has identified a novel syndrome that shares striking similarities with Smith-Lemli-Opitz syndrome (SLOS), potentially linked to prenatal exposure to fentanyl.

An initial cohort of 6 patients displayed hallmark features reminiscent of SLOS: microcephaly, short stature, and distinctive facial characteristics. Congenital malformations included cleft palate, talipes equinovarus or rocker bottom feet, and genitourinary anomalies such as chordee or hypospadias. Other notable findings were short, broad thumbs, a single palmar crease, and mild 2-3 toe syndactyly. Neuroimaging revealed a hypoplastic corpus callosum in 3 out of 5 patients evaluated.

These findings initially suggested SLOS. However, biochemical studies conducted shortly after birth indicated transient abnormalities in cholesterol metabolism, which resolved over time, differentiating this syndrome from classical SLOS. Extensive genetic testing failed to identify a common genomic cause.

A significant commonality among all cases was prenatal exposure to nonprescription opioids, particularly fentanyl. This observation led researchers to hypothesize that fentanyl exposure might disrupt cholesterol metabolism during fetal development, producing a phenotype that closely mimics SLOS.

The addition of 4 external cases with similar clinical findings strengthens the hypothesis that prenatal fentanyl exposure may contribute to this novel syndrome.

Reference
Erin Wadman E, Fernandes E, Muss C, et al. A novel syndrome associated with prenatal fentanyl exposure. Genetics in Medicine Open. 2023; https://doi.org/10.1016/j.gimo.2023.100834

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