Neurologic features of horizontal gaze palsy and progressive scoliosis with mutations in ROBO3.
OBJECTIVE
To review the neurologic, neuroradiologic, and electrophysiologic features of autosomal recessive horizontal gaze palsy and progressive scoliosis (HGPPS), a syndrome caused by mutation of the ROBO3 gene on chromosome 11 and associated with defective decussation of certain brainstem neuronal systems.


METHODS
The authors examined 11 individuals with HGPPS from five genotyped families with HGPPS. Eight individuals had brain MRI, and six had electrophysiologic studies.


RESULTS
Horizontal gaze palsy was fully penetrant, present at birth, and total or almost total in all affected individuals. Convergence, ocular alignment, congenital nystagmus, and vertical smooth pursuit defects were variable between individuals. All patients developed progressive scoliosis during early childhood. All appropriately studied patients had hypoplasia of the pons and cerebellar peduncles with both anterior and posterior midline clefts of the pons and medulla and electrophysiologic evidence of ipsilateral corticospinal and dorsal column-medial lemniscus tract innervation. Heterozygotes were unaffected.


CONCLUSIONS
The major clinical characteristics of horizontal gaze palsy and progressive scoliosis were congenital horizontal gaze palsy and progressive scoliosis with some variability in both ocular motility and degree of scoliosis. The syndrome also includes a distinctive brainstem malformation and defective crossing of some brainstem neuronal pathways.
Bosley
T M
TM
Neuro-ophthalmology Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. tmbosley@bosleynet.net
Salih
M A M
MA
Jen
J C
JC
Lin
D D M
DD
Oystreck
D
D
Abu-Amero
K K
KK
MacDonald
D B
DB
al Zayed
Z
Z
al Dhalaan
H
H
Kansu
T
T
Stigsby
B
B
Baloh
R W
RW
D000293:Adolescent; D000328:Adult; D001933:Brain Stem / Q000002:abnormalities / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D025063:Chromosome Disorders / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D009421:Nervous System Malformations / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D009434:Neural Pathways / Q000002:abnormalities / Q000503:physiopathology; D015835:Ocular Motility Disorders / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D010375:Pedigree; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000235:genetics*; D012600:Scoliosis / Q000235:genetics / Q000503:physiopathology*; D013577:Syndrome; D000097905:Roundabout Proteins
D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C499630:ROBO3 protein, human; D000097905:Roundabout Proteins