PURPOSE: To summarize the clinical, neuroradiologic, and genetic observations in a group of patients with unilateral synergistic divergence (SD). METHODS: Five unrelated patients with unilateral SD underwent ophthalmic and orthoptic examinations; three of them also had magnetic resonance imaging of the brain and orbits. Three patients underwent genetic evaluation of genes known to affect ocular motility: KIF21A, PHOX2A, HOXA1, and ROBO3. RESULTS: The patients did not meet the clinical criteria for CFEOM types 1, 2, or 3. Each patient had severe adduction weakness on the affected side and large-angle exotropia in primary gaze that increased on attempted contralateral gaze because of anomalous abduction. Magnetic resonance imaging revealed a much smaller medial rectus muscle in the involved SD orbit. Oculomotor cranial nerves were present in the one patient imaged appropriately. Genetic sequencing in three patients revealed no mutations in KIF21A, PHOX2A, HOXA1, or ROBO3. CONCLUSIONS: SD should be classified as a distinct congenital ocular motility pattern within congenital cranial dysinnervation disorders. It may be caused by denervation of the medial rectus with dysinnervation of the ipsilateral lateral rectus by the oculomotor nerve precipitated by genetic abnormalities (some currently identified) or by local environmental, teratogenic, or epigenetic disturbances.
PURPOSE: To summarize the clinical, neuroradiologic, and genetic observations in a group of patients with unilateral synergistic divergence (SD). METHODS: Five unrelated patients with unilateral SD underwent ophthalmic and orthoptic examinations; three of them also had magnetic resonance imaging of the brain and orbits. Three patients underwent genetic evaluation of genes known to affect ocular motility: KIF21A, PHOX2A, HOXA1, and ROBO3. RESULTS: The patients did not meet the clinical criteria for CFEOM types 1, 2, or 3. Each patient had severe adduction weakness on the affected side and large-angle exotropia in primary gaze that increased on attempted contralateral gaze because of anomalous abduction. Magnetic resonance imaging revealed a much smaller medial rectus muscle in the involved SD orbit. Oculomotor cranial nerves were present in the one patient imaged appropriately. Genetic sequencing in three patients revealed no mutations in KIF21A, PHOX2A, HOXA1, or ROBO3. CONCLUSIONS: SD should be classified as a distinct congenital ocular motility pattern within congenital cranial dysinnervation disorders. It may be caused by denervation of the medial rectus with dysinnervation of the ipsilateral lateral rectus by the oculomotor nerve precipitated by genetic abnormalities (some currently identified) or by local environmental, teratogenic, or epigenetic disturbances.
Authors: T M Bosley; M A M Salih; J C Jen; D D M Lin; D Oystreck; K K Abu-Amero; D B MacDonald; Z al Zayed; H al Dhalaan; T Kansu; B Stigsby; R W Baloh Journal: Neurology Date: 2005-04-12 Impact factor: 9.910
Authors: Max A Tischfield; Thomas M Bosley; Mustafa A M Salih; Ibrahim A Alorainy; Emin C Sener; Michael J Nester; Darren T Oystreck; Wai-Man Chan; Caroline Andrews; Robert P Erickson; Elizabeth C Engle Journal: Nat Genet Date: 2005-09-11 Impact factor: 38.330
Authors: Thomas M Bosley; Darren T Oystreck; Richard L Robertson; Abdulaziz al Awad; Khaled Abu-Amero; Elizabeth C Engle Journal: Brain Date: 2006-06-30 Impact factor: 13.501
Authors: M Nakano; K Yamada; J Fain; E C Sener; C J Selleck; A H Awad; J Zwaan; P B Mullaney; T M Bosley; E C Engle Journal: Nat Genet Date: 2001-11 Impact factor: 38.330
Authors: Elizabeth C Engle; Nathalie McIntosh; Koki Yamada; Bjorn A Lee; Roger Johnson; Michael O'Keefe; Robert Letson; Arnold London; Evan Ballard; Mark Ruttum; Naomichi Matsumoto; Nakamichi Saito; Mary Louise Z Collins; Lisa Morris; Monte Del Monte; Adriano Magli; Teresa de Berardinis Journal: BMC Genet Date: 2002-03-06 Impact factor: 2.797