The disorder was tested for linkage to two known autosomal dominant CFEOM loci on chromosome 12p11.2-q12 (CFEOM1) and chromosome 16q24 (CFEOM3) using microsatellite markers.
These observations led us to ask whether axon dysinnervation is a primary phenotype, and why the E421K, but not other, TUBB2B substitutions cause CFEOM.
This atypical form of CFEOM maps to the FEOM2 locus on chromosome 11q13 and results from mutations in ARIX (PHOX2A).(6,7) ARIX encodes a homeodomain transcription factor protein previously shown to be required for nIII/nIV development in mouse and zebrafish.
Congenital fibrosis of the extraocular muscles type 2 (CFEOM2) is a distinct non-syndromic form of congenital incomitant strabismus secondary to orbital dysinnervation from recessive mutations in the gene PHOX2A.
Three clinical phenotypes for familial CFEOM (CFEOM1, 2, and 3) have been delineated, for which two genes have been identified to date: KIF21A for CFEOM1 and 3 and PHOX2A/ARIX for CFEOM2.
We now identify additional pedigrees with CFEOM1 to determine if the disorder is genetically heterogeneous and, if so, if any affected members of CFEOM1 pedigrees or sporadic cases of classic CFEOM harbor mutations in ARIX, the CFEOM2 disease gene.
To determine whether congenital fibrosis of the extraocular muscles (CFEOM) with Marcus Gunn jaw-winking phenomenon (MG) can result from mutations in the KIF21A gene encoding a kinesin motor protein.
To demonstrate the clinical characteristics and determine mutations in the KIF21A gene, encoding a kinesin motor protein in patients with congenital fibrosis of the extraocular muscles (CFEOM) type 1.
To describe the phenotypic characteristics and clinical course of a sporadic case of congenital fibrosis of the extraocular muscles (CFEOM) and Möbius syndrome with a de novo mutation in the KIF21A gene encoding a kinesin motor protein.
RYR1-associated myopathies should be included in the differential diagnosis of congenital ophthalmoplegia and facial weakness, even without clinical skeletal myopathy.
A total of 13 patients with genetically confirmed CFEOM (via genetic testing for mutations in KIF21A, PHOX2A, and TUBB3) were retrospectively identified after undergoing strabismus surgery at Boston Children's Hospital and surgical outcomes were compared.
Here, we report three consanguineous families with biallelic homozygous loss-of-function mutations in MYF5 who define a clinical disorder characterized by congenital ophthalmoplegia with scoliosis and vertebral and rib anomalies.
Ophthalmic findings were present in 3 of the 4 siblings with ECEL1-related distal arthrogryposis: bilateral ptosis with bilateral congenital fibrosis of the extraocular muscles, right ptosis with ipsilateral Y exotropia (exotropia increasing in upgaze), and right ptosis with ipsilateral Duane retraction syndrome.
A major mutation of KIF21A associated with congenital fibrosis of the extraocular muscles type 1 (CFEOM1) enhances translocation of Kank1 to the membrane.