Clinical and MRI differences in congenital fibrosis of extraocular muscles patients with KIF21A and TUBB3 variants.

Purpose: To compare the clinical and neuroimaging phenotypes in Chinese patients with congenital fibrosis of extraocular muscles (CFEOM) harboring KIF21A versus TUBB3 variants.

Study Design: Retrospective, observational case series.

Methods: A retrospective review of 37 CFEOM patients harboring mutations of KIF21A (n = 25) and TUBB3 (n = 12) with clinical examinations was performed. MRI was used to evaluate orbital, encephalic, and intracranial nerve integrity. The diameters of oculomotor nerve (CN3) and abducens nerves (CN6), the cross-section area (CSA) of the optic nerve (ON) and the volumes of extraocular muscles (EOMs) were measured in the mutant groups and normal control group (n = 20).

Results: The CFEOM-KIF21A group had a slightly higher percentage of bilateral blepharoptosis (95% vs. 70%) and synergistic convergence (40% vs. 20%) compared with the CFEOM-TUBB3 group. The diameter of CN3 and the CSA of ON were significantly smaller in the mutant groups than the control. The median diameter of CN6 was smaller in the KIF21A group than in the TUBB3 group (P < 0.001). The median volumes of the superior rectus, lateral rectus, and inferior oblique muscle in the KIF21A group were significantly smaller than TUBB3 group. 10% of KIF21A families and 40% of TUBB3 families were accompanied by systemic congenital malformation (P = 0.070).

Conclusion: Most of the CFEOM-KIF21A patients occur as isolated cases, tend to suffer a more severe ocular phenotype and CN6 hypoplasia. CFEOM-TUBB3 patients tend to present with syndromic CFEOM, systemic involvement is mainly associated with brain malformations, and appear to have a clear genotype-phenotype correlation.