P217: Solving for PS4

confirmed when biological mother admitted to the exposure or when there was a positive toxicology screen for Fentanyl.We aimed to investigate the spectrum of malformations and abnormalities of growth and development associated with prenatal Fentanyl exposure.Results: This series is comprised of 23 cases, 15 males and 8 females, examined between a few days of life and 38 months.Of those, 2 were exposed to Fentanyl alone, 10 patients had additional exposure to methamphetamine, 2 patients were also exposed to alcohol, and the remainder were exposed to Fentanyl and at least two other substances including methamphetamines, alcohol, cannabis, heroin and/or methadone.Fifteen patients (65%) had significant feeding difficulties that persisted for several months or years, and 9 of them (39%) eventually required G tube placement.Whereas only 1 patient was born with low weight (<2 z-score for his gestational age), 9 cases (39%) developed failure to thrive, with low weight and length at the time of the exam.Similarly, only 2 patients had microcephaly at birth, while 11 (48%) had acquired microcephaly at the time of their last exam.The patients exhibit a distinct pattern of craniofacial features including bitemporal narrowing (6), ptosis (8), short anteverted nose (13), downturned corners of the mouth ( 14) and micro/retrognathia (11).Palate abnormalities were seen in 8 cases, ranging from bifid uvula to cleft palate.We identified club feet in 5 patients, and abnormal palmar creases in 14 patients.Three patients had significant 2-3 toe syndactyly, and 2 males had hypospadias.Global developmental delays were evident in 17 cases (74%), sometimes severe.Brain MRI was obtained in 13 patients and 2 had a thin corpus callosum, the rest did not have any abnormalities noted.Genetic testing was performed in 15 patients and did not identify a primary cause for the phenotype in any.Fourteen had chromosomal microarrays and 7 had gene panels and/or exome sequencing.Two siblings were found to have a likely pathogenic variant in COL3A1, an incidental finding consistent with a diagnosis of vascular Ehlers-Danlos syndrome.Biochemical studies of cholesterol metabolites were performed in 7 patients, and only the 2 that were tested in the first week of life had elevated 7-dehydrocholesterol. Conclusion: Prenatal exposure to Fentanyl may alter fetal growth and morphogenesis and most often affects growth and development in the postnatal period.Our case series supports the delineation of a novel syndrome associated with prenatal Fentanyl exposure.The Fetal Fentanyl Syndrome (FFS) is characterized by a distinctive combination of dysmorphic features, major malformations (cleft palate, club feet, hypospadias), feeding difficulties, growth deficits and developmental delays.Our results also indicate that there might be a Fetal Fentanyl Spectrum of Disorders (FFSD) that goes beyond FFS.Further studies are needed to better understand the variability of the consequences of the exposure to this newly recognized teratogen.