Abstract
Myogenic transcription factors with a basic helix-loop helix (bHLH) such as MYOD, myogenin, MRF4 and MYF5 contribute to muscle differentiation and regulation. The MYF5 gene located on chromosome 12 encodes for myogenic factor 5 (MYF5) which has a role in skeletal and extra-ocular muscle development and rib formation. Variants in MYF5 were found to cause external ophthalmoplegia with rib and vertebral anomalies (EORVA), a rare recessive condition. This entity can be easily mistaken with congenital fibrosis of extra-ocular muscles (CFEOM) which has a different pathogenesis and systemic features. To date, three homozygous variants in MYF5 have been reported to cause EORVA in six members of four unrelated families.
Here, we present a novel homozygous MYF5 frameshift variant, c.596dup, p.(Asn199Lysfs*49), causing premature protein termination and presenting with external ophthalmoplegia, ptosis and scoliosis in three siblings from a consanguineous family of Pakistani origin. With four MYF5 variants now discovered, we highlight the importance of undertaking genetic testing in all children with external ophthalmoplegia for correct diagnosis and management of systemic complications.
