Disease relevance of Duane Retraction Syndrome

• Blepharophimosis and bilateral Duane syndrome associated with a FOXL2 mutation [1].
• Although rare, Duane syndrome may occur in children with large angle esotropia, and its presence may not be revealed until after strabismus surgery [2].

High impact information on Duane Retraction Syndrome

• SALL4 represents the first identified Duane syndrome gene and the second malformation syndrome resulting from mutations in SAL genes and likely plays a critical role in abducens motoneuron development [3].
• Arising from our observation of several malformations in Okihiro syndrome patients which are also described in Townes-Brocks syndrome, we postulated that Okihiro syndrome might result from mutation of another member of the human SALL gene family [4].
• The index patient shows mild features of Okihiro syndrome, but in addition cranial midline defects (pituitary hypoplasia and single central incisor) [5].
• Mutations of human SALL4 have been linked to Okihiro syndrome, which includes preaxial (anterior) limb defects [6].
• Using both genomic and cDNA mouse and human clones encoding a neural-specific bHLH protein, human BHLHB5 was cloned and mapped to a region on chromosome 8q13 that segregates with Duane syndrome [7].

Biological context of Duane Retraction Syndrome

• Furthermore we confirm the overlap of acro-renal-ocular syndrome with Okihiro syndrome at the molecular level and expand the phenotype of SALL4 mutations [8].

Anatomical context of Duane Retraction Syndrome

• Prominent expression in the developing midbrain, branchial arches and the limbs suggests an important function of SALL4 during development of these structures as expected from the observation in Okihiro syndrome patients [9].

Gene context of Duane Retraction Syndrome

• The presence of CPA6 mRNA in the rectus muscle layer of the eye at embryonic day 14.5 is consistent with the observation that the CPA6 gene is disrupted in a patient with Duane syndrome, a congenital eye defect [10].
• 2. There is considerable overlap of clinical features of Okihiro syndrome with other conditions, most notably Holt-Oram syndrome, a condition in part resulting from mutation of the TBX5 locus, as well as acro-renal-ocular syndrome [8].
• This case describes the novel coexistence of sporadic blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and bilateral type I Duane syndrome in a female infant, with a FOXL2 mutation [1].
• Duane syndrome (MIM 126800) is an autosomal dominant disorder characterised by primary strabismus and other ocular anomalies, associated with variable deficiency of binocular sight [11].
• However, 44% had both Duane's syndrome and radial ray anomaly, whereas sensorineural deafness alone occurred in only 17% of patients [12].

References