A number sign (#) is used with this entry because of evidence that Duane retraction syndrome-3 with or without deafness (DURS3) is caused by heterozygous mutation in the MAFB gene (608968) on chromosome 20q12.

Duane retraction syndrome (DURS) is the most common congenital disorder of cranial dysinnervation, with a prevalence of 1 in 1,000 individuals. Affected individuals have limited unilateral or bilateral horizontal eye movement, accompanied by globe retraction and palpebral fissure narrowing on attempted adduction (movement of the eye inward, toward the nose). DURS can be classified into 3 types: type 1, the most common, involves limited abduction (movement of the eye outward toward the ear); type 2, the least common, involves limited adduction; and type 3 involves limitation of both abduction and adduction. MRI and postmortem examination of patients with DURS have shown absence or hypoplasia of the abducens nerve, which normally innervates the lateral rectus (LR) extraocular muscle to abduct the eye, as well as aberrant LR muscle innervation by axons of the oculomotor nerve, which normally innervates the medial, inferior, and superior rectus and inferior oblique extraocular muscles (summary by Park et al., 2016).

For a discussion of genetic heterogeneity of Duane retraction syndrome, see DURS1 (126800).

Park et al. (2016) studied a family (family FA) in which autosomal dominant Duane retraction syndrome cosegregated with congenital sensorineural hearing loss as a dominant trait. An affected mother and son had unilateral DURS and deafness, both right-sided; the mother had type 1 DURS, with only limited abduction of the eye, whereas the son had type 3 DURS, with limitation of both abduction and adduction of the eye. A second affected son, who had unilateral right-sided type 1 DURS, did not report deafness, but had not undergone formal hearing testing. He also had an affected daughter, who had bilateral type 3 DURS and deafness. Axial CT images of the daughter's right temporal bone revealed a cystic common-cavity anomaly.

The transmission pattern of Duane retraction syndrome in the family reported by Park et al. (2016) was consistent with autosomal dominant inheritance.

Park et al. (2016) stated that Duane retraction syndrome has a prevalence of 1 in 1,000 individuals.

In a family (FA) segregating autosomal dominant DURS and hearing loss known to be negative for mutation in the HOXA1 gene (142955), Park et al. (2016) analyzed the candidate gene MAFB and identified heterozygosity for a 1-bp deletion (608968.0007) in affected individuals. Screening of MAFB in 400 probands with DURS and in 10 probands with both DURS and hearing loss identified 2 more DURS families with heterozygous 1-bp deletions (608968.0008-608968.0009) and 1 with a heterozygous full gene deletion (608968.0010). None of the affected individuals in the 3 additional mutation-positive families had hearing loss. Functional analysis suggested a threshold model for variable loss of MAFB function: the mutation in family FA showed a dominant-negative effect, resulting in less than 50% protein function and causing both DURS and deafness, consistent with absent abducens nerves and inner-ear defects in Mafb knockout mice, whereas the heterozygous loss-of-function mutations in the other 3 families showed 50% protein function and caused isolated DURS, consistent with DURS pathology and normal inner-ear development in Mafb heterozygous mice.