Prenatal exposure to fluconazole: an identifiable dysmorphic phenotype

Fluconazole is a triazole antifungal used to treat mycotic infections. Fluconazole is reported to act as a teratogen when used continuously at a dosage of 400-800 mg daily. Fluconazole embryopathy was previously reported in 4 cases. The common features that were also seen in the current case include multiple synostosis (including craniosynostosis and digital synostosis), congenital heart defects, skeletal anomalies, and recognizable dysmorphic facial features.

We report the case of a 9-month-old male born to a 30-year-old woman following a 37-week pregnancy. The pregnancy was complicated by maternal human immunodeficiency virus (HIV) infection and multiple drug exposures, including fluconazole (400 mg/day) until the fifth month and then from 6 months to term, efavirenz, nevirapine, methadone, dapsone, pentamidine, and trimethoprim-sulfamethoxazole. At birth the infant had seizures related to neonatal abstinence syndrome and was noted to have multiple congenital anomalies. On examination at age 9 months, he had craniosynostosis secondary to coronal and lambdoidal suture closures, shallow orbital region, hypoplastic supraorbital ridges, hypertelorism, and mild ptosis. He had radioulnar synostosis and metacarpophalangeal-proximal interphalangeal symphalangism of D2-D5 bilaterally.

The findings of cranial synostosis, multiple symphalangism, and long-bone abnormalities in our case are typical of other reported cases of fluconazole embryopathy. Our patient showed no evidence of embryopathy due to efavirenz, and he did not have the features of Antley-Bixler or other craniosynostosis syndromes. We review the literature regarding the teratogenic effects of prenatal exposure to fluconazole and provide additional evidence that prenatal fluconazole exposure has a clearly identifiable phenotype.