Tubulin Mutations and Ophthalmic Manifestations: A Paediatric Case Series
Vasiliki Panteli, MD, PhD, FEBO; Alki Liasis, BSc, PhD; Richard Bowman, MD, FRCOphth
Clinical and Academic Department of Ophthalmology, Great Ormond Street Hospital for Children
Introduction: Tubulinopathies are a wide and overlapping range of brain malformations caused by six known gene mutations of different tubulin isotypes. Brain abnormalities include a range of lissencephalies and polymicrogyria-like cortical dysplasias with additional structural cerebral anomalies. Ocular findings involve associated cortical visual impairment, Congenital Fibrosis of Extraocular Muscles (CFEOM) and associated ptosis, strabismus, and less commonly optic nerve hypoplasia. We present an observational case series of children diagnosed with a tubulinopathy, with emphasis on ophthalmic manifestations.
Methods: Six children with genetically confirmed variants of TUBA1A, TUBB2B and TUBB3 gene, presenting at Great Ormond Street Hospital for Children, were included. All children underwent full ophthalmic examination including orthoptic assessment, anterior and posterior segment examination, cycloplegic refraction and electrophysiology.
Results: Ocular abnormalities involved CFEOM (3/6 patients), bilateral ptosis (3/6), strabismus (6/6), optic nerve hypoplasia (3/6), nystagmus (2/6), and visual impairment of varying degree (6/6). Eletrophysiology showed normal electroretinogram in five cases and borderline cone dysfunction in one, abnormal pattern Visual Evoked Potential (VEP) in four and abnormal flash VEP in three.
Discussion: One case of TUBB3 mutation with cone dysfunction (association not previously reported) was identified. Strabismus, ocular motility defects and ptosis were common. Optic nerve hypoplasia previously described in one specific variant was more common in this study.
Conclusion: Ocular manifestations in tubulinopathies vary in severity. Management of the neuro-ophthalmological problems can be challenging. Early recognition by the ophthalmologist and association with non-ocular clinical and radiological findings may allow clinicians to identify individuals and guide genetic investigation to establish diagnosis.
References: Bahi-Buisson N, Cavallin M. Tubulinopathies overview.In:Pagon RA, Adam MP,eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017; 2016:1-15.