A novel syndrome was suspected in individuals sharing short stature, microcephaly, distinctive facial features, and congenital anomalies. We enrolled 6 patients in an institutional review board approved study and evaluated medical history, findings, facial photographs, and test results across this original cohort. Four additional cases with similar findings were contributed by clinicians from outside institutions, bringing the number of reported cases to 10 and supporting the existence of this novel syndrome.

The 6 individuals enrolled into the institutional review board approved study shared microcephaly, short stature, and distinctive facial features. Congenital malformations included cleft palate, talipes equinovarus or rocker bottom feet, and chordee or hypospadias. Short, broad thumbs, single palmar crease, and mild 2,3 toe syndactyly were present. A hypoplastic corpus callosum was noted in 3 of 5 with appropriate evaluation. Their growth and physical findings were suggestive of Smith-Lemli-Opitz syndrome. Biochemical studies shortly after delivery indicated abnormalities in the cholesterol metabolism pathway that subsequently resolved. No shared genomic or genetic cause was identified. All individuals were born after a pregnancy complicated by prenatal exposure to nonprescription opioids, particularly fentanyl, suggesting fentanyl as a teratogen...