Figure 1. Clinical spectrum and orbital imaging of the TUBB3 syndromes.

(A–I) Study participant photographs. R262C can cause bilateral ptosis and severe CFEOM3 with the resting position of both eyes infraducted and abducted (A), moderate CFEOM3 that can be unilateral (B), and mild CFEOM3 (not shown). A similar spectrum is seen with D417N; severe CFEOM3 is shown in (E). A302T (C) and R380C (D) cause moderate to severe CFEOM3. Participants in (A–E) have full facial movements. The axonal neuropathy in the participant with D417N (E) results in atrophy of the intrinsic foot muscles and a high arch (F). E410K (G) and R262H (H) result in severe CFEOM3 and facial weakness, and R262H also results in congenital ulnar deviation of the hand with joint contractures of the thumbs and fingers (I). (J–L) MRI of the brainstem at the level of the oculomotor nerve (J) and orbital contents posterior to the globe (K) in a participant with predominantly left-sided CFEOM3 and a D417N substitution. Note unilateral hypoplasia of the left oculomotor nerve (J, arrow) and the atrophy of the levator palpebrae superioris (LPS), superior rectus (SR), and medial rectus (MR) muscles in (K). The inferior rectus (IR), lateral rectus (LR), and superior oblique (SO) muscles appear normal. (L) Control orbital MRI for comparison. (ON) denotes optic nerve.