Patients with horizontal gaze palsy and progressive scoliosis due to ROBO3 E319K mutation have both uncrossed and crossed central nervous system pathways and perform normally on neuropsychological testing

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 77; no. 9; pp. 1047 - 1053
• Main Authors: Amoiridis, G, Tzagournissakis, M, Christodoulou, P, Karampekios, S, Latsoudis, H, Panou, T, Simos, P, Plaitakis, A
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.09.2006; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: BAEP; Biological and medical sciences; brain stem auditory evoked potential; Cognition; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Progression; Electromyography; EMG; Evoked Potentials, Somatosensory; FDI; first dorsal interosseus; HGPPS; horizontal gaze palsy and progressive scoliosis; Humans; Intelligence tests; Magnetic Resonance Imaging; Male; Medical sciences; Middle Aged; Mitochondrial DNA; Motor ability; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Mutation; Nervous system; Neurologic Examination; Neurology; Neuropsychological Tests; NMR; Nuclear magnetic resonance; Ocular Motility Disorders - complications; Ocular Motility Disorders - genetics; Ocular Motility Disorders - physiopathology; Patients; Perception; Pyramidal Tracts - pathology; Pyramidal Tracts - physiology; Reading; Receptors, Immunologic - genetics; Scoliosis; Scoliosis - complications; Scoliosis - genetics; Scoliosis - physiopathology; SSR; sympathetic skin response; Human; Nervous system diseases; Deformation; Gaze; Scoliosis; Diseases of the osteoarticular system; Central nervous system; Spine disease; Mutation
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp.2006.088435

Background: Horizontal gaze palsy and progressive scoliosis (HGPPS) is caused by mutations of the ROBO3 gene, which encodes a receptor associated with axonal guidance during development. Although there is evidence for uncrossed cuneatal and corticospinal tracts in HGPPS, it is unclear whether other central nervous system pathways are involved. Objective: To study two patients with HGPPS homozygotic for the ROBO3 E319K mutation using a variety of neurophysiological and neuropsychological tests. Methods: A battery of neuropsychological tests was applied to assess various cognitive and perceptual functions. The corticospinal, somatosensory and auditory pathways were evaluated using appropriate neurophysiological tests. To access motor pathways to the neck muscles, electromyographic recordings were obtained from the sternocleidomastoideus and splenius capitis muscle during active head rotation. Results: Both patients performed normally on manual dexterity, complex sensory and visuospatial functions, reading and general intelligence tests. Motor evoked potentials in both patients showed uncrossed corticospinal tracts for the extremities, although in one patient, electromyography indicated pyramidal tract crossing for the neck muscles. Although somatosensory evoked potentials showed uncrossed somatosensory fibres subserving proprioception and light touch, right median nerve somatosensory evoked potential in one patient indicated a partial lemniscal crossing. Sympathetic skin response and blink reflex showed a midline crossing of the spinothalamic and quintothalamic tracts. Brain stem auditory evoked potentials indicated a lack of crossing in the level of the trapezoid body. Conclusions: Our patients with the ROBO3 E319Κ mutation show normal perceptual and cognitive functions and have both crossed and uncrossed motor, sensory and auditory pathways.