Hypomyelinating leukoencephalopathy with paroxysmal tonic upgaze and absence of psychomotor development

Abstract

Hypomyelinating leukoencephalopathies are characterized by a substantial and permanent deficit in myelin deposition in the brain. Although our knowledge and understanding of the etiology of white matter diseases has progressively increased, many cases with this disorder remain undiagnosed, despite extensive evaluations. Recently, new disease entities have been defined by combining magnetic resonance imaging pattern recognition and clinical features. We describe a 1-year-old Ashkenazi Jewish girl with a hypomyelinating leukoencephalopathy, who presented in the neonatal period with episodes of sustained paroxysmal tonic upward gaze, roving eye movements, pendular nystagmus, and severe hypotonia, with the later appearance of pyramidal and extrapyramidal signs and no development. In addition, she has dysmorphic signs. This clinical picture is not consistent with any of the previously described hypomyelinating leukoencephalopathies and may represent a new entity.

Oculogyric crises: A review of phenomenology, etiology, pathogenesis, and treatment

“…Paroxysmal tonic upgaze has also been described in children with cerebellar ataxia and developmental delay caused by mutations in GRID2, and in sporadic cases of Beckwith‐Wiedemann syndrome, genetically undefined hypomyelinating leukoencephalopathy, CACNA1A mutation with episodic ataxia, and childhood absence epilepsy . Again, at this time, it is not clear whether these represent OGC or some other ocular movement disorder.…”

Paroxysmal Tonic Upgaze Presenting as a Clinical Isolated Syndrome

“…4,6 Recently, Blumkin et al reported a patient whose cranial magnetic resonance imaging demonstrated severe hypomyelination, thin corpus callosum, and progressive brain atrophy. 2 As a result, in consideration for the paroxysmal tonic upgaze cases with delayed myelination, hypomyelination, or demyelination, as in our case, disorder of myelin can be important in the pathogenesis of paroxysmal tonic upgaze. Neuroimaging must be performed in all cases with paroxysmal tonic upgaze.…”

“…1 In the further cases with paroxysmal tonic upgaze learning disabilities, abnormal neurologic findings such as ataxia, chromosomal abnormality, familial inheritance, and abnormal neuroimaging findings have also been reported. [2][3][4][5][6] We report a patient who had paroxysmal tonic upgaze and demyelinating lesions on his cranial magnetic resonance imaging.…”

Paroxysmal tonic upgaze accompanied by occipital discharge on electroencephalography: a case report and literature review

“…The reported results of imaging studies for most children with PTU have been normal, with the exception of some cases with hypomyelination or delayed myelination, or with lesions within the oculomotor pathway, 12,13 which is mostly located within the midbrain and brainstem.…”