Synergistic divergence: a distinct ocular motility dysinnervation pattern.
OBJECTIVE
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.
Oystreck
Darren T
DT
Pediatric Ophthalmology Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
Khan
Arif O
AO
Vila-Coro
Antonio Aguirre
AA
Oworu
Olugbemisola
O
Al-Tassan
Nada
N
Chan
Wai-Man
WM
Engle
Elizabeth C
EC
Bosley
Thomas M
TM
D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005133:Eye Movements; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D016547:Kinesins / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D009121:Muscle Denervation; D015835:Ocular Motility Disorders / Q000151:congenital* / Q000235:genetics; D009801:Oculomotor Muscles / Q000294:innervation*; D009802:Oculomotor Nerve / Q000002:abnormalities*; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000235:genetics; D014057:Tomography, X-Ray Computed; D014157:Transcription Factors / Q000235:genetics; D000099261:Homeobox A1 Protein; D000097905:Roundabout Proteins
D018398:Homeodomain Proteins; D016547:Kinesins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D014157:Transcription Factors; D000099261:Homeobox A1 Protein; C119023:KIF21A protein, human; C491061:PHOX2A protein, human; C499630:ROBO3 protein, human; D000097905:Roundabout Proteins