CONGENITAL FIBROSIS OF THE EXTRAOCULAR MUSCLES (CFEOM)

KIF21A, TUBB3 AND PHOX2A GENE ANALYSIS 

Congenital fibrosis of the extraocular muscles (CFEOM) describes a group of rare congenital non-progressive eye movement disorders characterized by congenital non-progressive ophthalmoplegia (inability to move the eyes) typically with ptosis (droopy eyelids) affecting part or all of the oculomotor nucleus and nerve (cranial nerve III) and its innervated muscles (superior, medial, and inferior recti, inferior oblique, and levator palpabrae superioris) and/or the trochlear nucleus and nerve (cranial nerve IV) and its innervated muscle (the superior oblique).

Autosomal dominant variants in the KIF21A and TUBB3 genes cause CFEOM type 1 (Yamada et al. 2003 Nat Genet 35,4:318, Tischfield et al. 2010 Cell 140,1:74-87). CFEOM type 2 is an autosomal recessive disorder and is due to disease-causing variants in the PHOX2A gene (also known as ARIX) (Nakano et al. 2001 Nat Genet 29:315-320). CFEOM type 3 is inherited in an autosomal dominant manner with incomplete penetrance and variable expressivity, and is caused by disease-causing variants in the TUBB3 gene (CFEOM type 3A) (Tischfield et al. 2010 Cell 140:74-87). Disease-causing variants in the KIF21A gene have also been identified in 20% of individuals with CFEOM type 3 (Yamada et al. 2004 Invest Opthal & Vis Sci 45:2218-2223, Lu et al. 2008 Arch Opthalmol 126,3:388-394).

The laboratory participates in the European Molecular Genetics Quality Network (EMQN) sequencing scheme.