Duane retraction syndrome (DURS) is a congenital disorder characterized by restricted horizontal eye movement with globe retraction and palpebral fissure narrowing on attempted adduction. DURS is observed in approximately 0.1% of the general population, accounts for 1 to ... Duane retraction syndrome (DURS) is a congenital disorder characterized by restricted horizontal eye movement with globe retraction and palpebral fissure narrowing on attempted adduction. DURS is observed in approximately 0.1% of the general population, accounts for 1 to 5% of all strabismus, and if untreated in childhood can result in loss of binocular vision and amblyopia. Postmortem examinations of individuals with sporadic DURS have shown absence of the abducens motor neurons and abducens cranial nerve on the affected side(s), and aberrant innervation of the lateral rectus by axons of the oculomotor nerve that normally innervate the medial rectus muscle. Most patients are affected unilaterally and have no family history of the disorder (summary by Miyake et al., 2010). For a discussion of genetic heterogeneity of Duane retraction syndrome, see DURS1 (126800).
Appukuttan et al. (1999) reported a large 4-generation Mexican family in which 25 living members were affected with Duane anomaly transmitted in an autosomal dominant pattern. Chung et al. (2000) studied 110 of the family members and examined ... Appukuttan et al. (1999) reported a large 4-generation Mexican family in which 25 living members were affected with Duane anomaly transmitted in an autosomal dominant pattern. Chung et al. (2000) studied 110 of the family members and examined the 25 patients in detail. None of the unaffected family members had evidence of neurologic abnormalities. All but 1 of the 25 patients had bilateral Duane anomaly of type 1 or type 3, and there was a high prevalence of manifest strabismus (76%) and amblyopia (48%). In 1 family subgroup, 3 patients had a unilateral fourth cranial nerve palsy. Other ophthalmic and neurologic abnormalities included unilateral congenital ptosis, upper eyelid retraction with downgaze, unilateral congenital deafness, nystagmus, and seizures, each observed in 1 patient. None of the patients had visible external ear or facial anomalies. Evans et al. (2000) described a 4-generation family in the United Kingdom with autosomal dominant transmission of isolated bilateral Duane syndrome. Of 9 affected family members, 5 cases were type 1 bilaterally, 2 cases were type 3 bilaterally, and 2 cases were type 1 in the right eye and type 3 in the left eye. Eight cases had a primary position esotropia, and there was a vertical eye movement abnormality in 8 cases, 5 with a 'V' configuration and 3 with an 'A' configuration. Demer et al. (2007) used high-resolution, multipositional MRI in a study of 5 male and 3 female affected members of 2 families with autosomal dominant Duane retraction syndrome mapping to chromosome 2. All patients had unilateral or bilateral limitation of abduction, or of both abduction and adduction, with palpebral fissure narrowing and globe retraction in adduction. Orbital motor nerves were typically small, with the abducens nerve (cranial nerve 6; CN6) often nondetectable. Lateral rectus muscles were structurally abnormal in 7 patients, with structural and motility evidence of oculomotor nerve (CN3) innervation from vertical rectus extraocular muscles (EOM) leading to A or V patterns of strabismus in 3 cases. Four cases had superior oblique, 2 cases superior rectus, and 2 cases levator EOM hypoplasia. Only the medial and inferior rectus and inferior oblique EOMs were spared. Two cases had small CN3s. Demer et al. (2007) concluded that DURS2 is a diffuse congenital cranial dysinnervation disorder involving but not limited to CN6. Miyake et al. (2011) reported 5 family members with distinctive ocular dysmotility patterns that cosegregated with a novel hyperactivating CHN1 mutation. All 5 clinically affected family members exhibited monocular or binocular supraduction deficits, 3 in the absence of DURS2. MRI in 4 affected individuals demonstrated small or absent abducens nerves in all 4, small oculomotor nerve in 1, and small optic nerves in 3. Superior oblique muscle volume was also decreased in 3 of the individuals, supporting trochlear nerve hypoplasia. Miyake et al. (2011) concluded that their analysis of this pedigree expanded the phenotypic spectrum of hyperactivating CHN1 mutations to include vertical strabismus and supraduction deficits in the absence of Duane retraction syndrome.
Miyake et al. (2008) identified 7 heterozygous missense changes in the CHN1 gene (118423), which encodes 2 Rac-specific guanosine triphosphatase (GTPase)-activating alpha-chimerin isoforms. All 7 nucleotide substitutions cosegregated with the affected haplotypes. None were present in online SNP ... Miyake et al. (2008) identified 7 heterozygous missense changes in the CHN1 gene (118423), which encodes 2 Rac-specific guanosine triphosphatase (GTPase)-activating alpha-chimerin isoforms. All 7 nucleotide substitutions cosegregated with the affected haplotypes. None were present in online SNP databases or on 788 control chromosomes. Five of the 7 resulted in nonconservative amino acid substitutions. All were predicted to alter amino acids that are conserved in 8 different species. Miyake et al. (2010) screened the CHN1 gene in 140 sporadic patients with Duane retraction syndrome but did not detect any mutations, in contrast to the 35% detection rate of CHN1 mutation in familial DURS (7 of 20 pedigrees; Miyake et al., 2008). Miyake et al. (2010) concluded that CHN1 mutations are not a major cause of DURS among patients with sporadic disease. In 2 families segregating Duane retraction syndrome-2, Chan et al. (2011) identified heterozygous gain-of-function mutations in the CHN1 gene (118423.0008-118423.0009).