Mimicking inherited eye disease

Congenital fibrosis of the extraocular muscles (CFEOM) is a rare, inherited eye disease with several different forms. CFEOM1 results from an inherited dominant mutation in the kinesin family member 21A (KIF21A) gene, whereas CFEOM2 comes about from a recessive mutation on the paired-like homeobox 2a (PHOX2A) gene. One major difference between the two phenotypes is that CFEOM2 involves poorly reactive pupils.

However, in a study of a Jordanian family, researchers from the King Khaled Eye Specialist Hospital, and the King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, identified a clinically recessive form of CFEOM that in fact was associated with dominant mutation in the KIF21A gene.

The family consisted of two parents with six offspring. The parents and four of the children showed no symptoms, whereas the other two siblings showed signs of the disease including exotropia (outward deviation of the eyes), almost complete ophthalmoplegia (paralysis of the muscles controlling eye movement) and sluggish pupils.

Sequencing of the KIF21A gene revealed a mutation in the two affected individuals that was absent from the parents and the other siblings, showing a form of parental germline mosaicism. According to the researchers, this is the first such reported case for CFEOM. This specific KIF21A mutation is unlike all others in that it is associated with sluggish pupils.

The researchers suggest that such cases are probably under-recognized, leading to false diagnoses. Thus, ophthalmologists should keep this condition in mind when counselling families with apparent recessive or de novo mutations.

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