OMIM ID:
Fibrosis of Extraocular Muscles, CFEOM2
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
This is a congenital, autosomal recessive, nonprogressive type of CFEOM which has been described in several consanguineous Middle Eastern families. The responsible mutations are in a different gene than the one responsible for autosomal dominant CFEOM1 cases although some of the clinical features are similar. However, in CFEOM2 the eyes are less likely to be infraducted and instead are often fixed in extreme abduction. In addition, the phenotype is more variable with some eyes fixed in the ‘neutral’ position and others having more mobility than usually seen in CFEOM1 but the clinical heterogeneity is less than that seen in CFEOM3. Ptosis is part of both phenotypes. All patients have severe restrictions in ocular motility. It has been suggested that CEFOM2 patients are likely to have involvement of both superior and inferior divisions of the oculomotor nerve whereas only the superior division is abnormal in CFEOM1. Binocular vision is absent and amblyopia is common. The pupils may be small and respond poorly to light. Refractive errors are common.
Based on visual field testing and ERG findings, it has been suggested that subnormal vision in CFEOM2 may be due to undescribed retinal dysfunction.
Systemic Features
Mild facial muscle weakness may be apparent.
Genetics
Inheritance
This is an autosomal recessive disorder caused by homozygous mutations in the PHOX2A gene at 11q13.3-q13.4. Another more common form of CFEOM is the autosomal dominant CFEOM1 type (135700) in which the primary fixed deviation is infraduction. The third type is CFEOM3 (600638, 609384) which is clinically more heterogeneous.
Other nonsyndromal forms of congenital fibrosis of extraocular muscles include: CFEOM3C (609384), CFEOM5 (616219), and CFEOM with synergistic divergence (609612). See also Tukel CFEOM syndrome (609428).
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.