Lubov Blumkin, Esther Leshinsky-Silver, Ayelet Zerem, Sara Kivity, Dorit Lev, Tally Lerman-Sagie
Paroxysmal tonic upward gaze (PTU) was described by Ouvrier and Billson (1988) as an apparently benign phenomenon with negative investigations and eventual complete resolution of symptoms. A later review of 45 additional cases and other publications have demonstrated that a similar clinical picture may arise from structural brain lesions, channelopathies, neurotransmitter disorders, and epileptic seizures. CACNA1A related disorders manifest in a wide spectrum of paroxysmal neurological disorders: episodic ataxia 2, hemiplegic migraine, benign paroxysmal torticollis of infancy, paroxysmal vertigo. PTU as a phenomenon in patients with mutations in the CACNA1A gene has been only reported once.
We present three patients with multiple episodes of paroxysmal tonic upward gaze deviation that appeared during the first months of life. These patients demonstrated motor and language delay and later developed cerebellar symptoms and signs due to progressive cerebellar atrophy. Sequence analysis of the CACNA1A gene in one patient and whole exome sequencing in the other patients revealed 3 different de-novo mutations in the CACNA1A gene.
The combination of PTU with developmental delay or cerebellar signs in young patients may be indicative for CACNA1A mutations.