NF2-related schwannomatosis: A view from within the inner ear

Abstract

NF2-related schwannomatosis (NF2-SWN, formerly known as neurofibromatosis type 2) is an autosomal dominant disorder associated with the growth of bilateral schwannomas on the cochleo-vestibular nerves and meningiomas. NF2-SWN is caused by pathogenic variations in the NF2, moesin-ezrin-radixin-like (MERLIN) tumour suppressor gene. The mostly benign tumours can cause progressive sensorineural hearing loss, tinnitus and balance dysfunction. Outside the inner ear, tumours grow on other intra-cranial nerves, leading to further neurological issues and shortened life-expectancy. Here we re-evaluate some historic cases from our human temporal bone collection, and we review similar instances from the literature to highlight the structural and functional effects of such tumours on the cochlea and vestibular organs. Tumour growth is associated with the remodelling of sensory and ion-transporting epithelia, the loss of afferent neurons and hair cells, and signs of fluid dysregulation. These cases demonstrate the aggressive nature of this disease and the difficulties of surgically excising the bilateral tumours. They also emphasise the need for novel therapies that can slow or prevent tumour growth to preserve sensory function in people living with NF2-SWN.