Multiple Temporal Bone Anomalies in Isotretinoin Syndrome

Abstract

Vitamin A and its derivatives are known teratogens. To our knowledge, this is the second temporal bone histopathologic report on anomalies related to these substances. A white boy (aged 4 years 5 months at death) was born with a complex central nervous system dysgenesis related to his mother's use of isotretinoin (Accutane) early in pregnancy. Histopathologic examination revealed multiple anomalies in the temporal bones: a narrow external auditory canal, protrusion of bone marrow into the middle ear cavity, anomalies of the ossicles, hypoplasia of the facial nerve, absence of the chorda tympani nerve and the stapedius muscle, anomalies of the membranous labyrinth in the vestibule, a hypoplastic lateral semicircular canal, and a large vestibular aqueduct and endolymphatic sac.

A Scoping Review of Human Teratogens and Their Impact on the Developing Brain: A Contribution From the ConcePTION Project

“…2010; Barbero, Lotersztein et al. 2004; Ishijima and Sando 1999; Kritzinger and Steenkamp 2006; Lott et al. 1985; Rappaport and Knapp 1989; Rizzo et al.…”

Temporal Bone Pathology in Fetuses Exposed to Isotretinoin

“…made the insertion of cochlear implants very problematic, as suggested by Ishijima and Sando [8]. If these fetuses had survived, it is likely that they could have presented with a hearing deficit, which, in the absence of obvious dysmorphism, may not have been attributed to isotretinoin exposure.…”

Molecular Signaling in Retinoic Acid-Induced Inner Ear Teratogenesis

“…The critical period for exposure appears to be two to fi ve weeks postconception in the human, although this may not be clinically exact [32]. The deformities include anotia, aural atresia, microtic, low-placed and dorsally situated pinna, and narrowing of the external auditory canal [28,29]. Patients with microtia and atresia are usually characterized by conductive hearing loss in the affected ear.…”

“…Histological studies of the temporal bone in affected humans are limited, but show similarities to the teratogenetically induced defects in the mouse and rat embryos. Examination of human fetuses born to mothers receiving isotretinoin before and/or during the fi rst weeks of gestation demonstrate a slit-like tympanic cavity, anteriorly shifted or malformed incus, medially displaced or anomalous malleus, and deformities of the stapes [7,29]. A hypoplastic facial nerve and absence of the chorda tympani nerve and stapedius muscle have been reported [29].…”

“…Examination of human fetuses born to mothers receiving isotretinoin before and/or during the fi rst weeks of gestation demonstrate a slit-like tympanic cavity, anteriorly shifted or malformed incus, medially displaced or anomalous malleus, and deformities of the stapes [7,29]. A hypoplastic facial nerve and absence of the chorda tympani nerve and stapedius muscle have been reported [29]. Since the malformed tissues originate from the fi rst and second branchial arches, with the facial nerve also being one of the nerves of those arches, retinoidinduced embryopathies of the middle ear are likely to be due to early effects of retinoic acid on the fi rst and second arches [23].…”