# Clinical and genetic characteristics of Chinese patients with congenital fibrosis of the extraocular muscles

## TL;DR

This study examines the clinical and genetic features of Chinese patients with a rare eye movement disorder called congenital fibrosis of the extraocular muscles.

## Contribution

The study identifies a novel KIF21A gene variant and expands the known genetic spectrum of CFEOM in Chinese patients.

## Key findings

- Most CFEOM1 patients with KIF21A mutations had isolated CFEOM, while TUBB3 mutations in CFEOM3 patients showed varied clinical outcomes.
- A new KIF21A variant (c.3906T > A, p.D1302E) was identified, contributing to the genetic understanding of CFEOM.
- MRI findings showed diverse abnormalities, including muscle attenuation and cranial nerve dysgenesis.

## Abstract

This study aimed to describe the clinical and genetic characteristics of Chinese patients with congenital fibrosis of the extraocular muscles (CFEOM), and to evaluate the phenotype–genotype correlations in these patients.

This was a retrospective study. Patients with CFEOM underwent detailed ophthalmic examinations and magnetic resonance imaging (MRI). Panel-based next-generation sequencing was performed to identify pathogenic variants of disease-causing genes.

Sixty-two patients with CFEOM were recruited into this study. Thirty-nine patients were diagnosed with CFEOM1 and 23 with CFEOM3. Forty-nine of the 62 patients with CFEOM carried either KIF21A (41/49) or TUBB3 variants (8/49). Six known missense variants in the KIF21A and TUBB3 genes, and a novel variant (c.3906T > A, p.D1302E) in the KIF21A gene were detected. Most patients with CFEOM1 carrying the KIF21A mutation displayed isolated CFEOM, whereas patients with CFEOM3 carrying the TUBB3 mutation had a wide range of clinical manifestations, either CFEOM alone or syndromes. Nystagmus was also present in 12 patients with CFEOM. Furthermore, the MRI findings varied, ranging from attenuation of the extraocular muscles to dysgenesis of the cranial nerves and brain structure.

The novel variants identified in this study will further expand the spectrum of pathogenic variants in CFEOM-related genes. However, no phenotype–genotype correlations were established because of the diversity of the clinical characteristics of these patients.

The online version contains supplementary material available at 10.1186/s13023-024-03206-w.