Paroxysmal tonic upgaze in a patient with congenital ataxia due to a de novo missense variant of CACNA1G



      Paroxysmal tonic upgaze (PTU), defined as an involuntary upward movement of the eyes, has been considered as a benign phenomenon but may also be associated with ataxia and developmental delay. To date, CACNA1G mutations have been reported in autosomal dominant spinocerebellar ataxia designated SCA42 and in early encephalopathies with cerebellar atrophy but never in periodic childhood manifestations of PTU type.

      Case Report.

      We report the case of a 2-month-old infant with a de novo pathogenic variation of CACNA1G who presented PTU associated with congenital ataxia and other periodic neurological manifestations.


      Although the link between CACNA1G mutations and periodic neurological manifestations remains unclear, we provide detailed video documentations of PTU, paroxysmal torticollis and ataxia in a patient with a CACNA1G mutation. This case allows a better understanding of the underlying mechanisms of PTU and suggest potential new avenues for clinical treatments.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Pediatric Neurology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Ouvrier R.A.
        • Billson F.
        Benign paroxysmal tonic upgaze of childhood.
        J Child Neurol. 1988; 3: 177-180
        • Zhang L.P.
        • Jia Y.
        • Wang Y.P.
        Identification of Two de novo Variants of CACNA1A in Pediatric Chinese Patients With Paroxysmal Tonic Upgaze.
        Front Pediatr. 2021; 9 (722105. Published 2021 Sep 24. doi:10.3389/fped.2021.722105)
        • Chemin J.
        • Siquier-Pernet K.
        • Nicouleau M.
        • et al.
        De novo mutation screening in childhood-onset cerebellar atrophy identifies gain-of-function mutations in the CACNA1G calcium channel gene.
        Brain. 2018; 141 (180): 1998
        • Morino H.
        • Matsuda Y.
        • Muguruma K.
        • et al.
        A mutation in the low voltage-gated calcium channel CACNA1G alters the physiological properties of the channel, causing spinocerebellar ataxia.
        Mol Brain. 2015; 8 (Published 2015 Dec 29): 89
        • Gazulla J.
        • Izquierdo-Alvarez S.
        • Ruiz-Fernández E.
        • Lázaro-Romero A.
        • Berciano J.
        Episodic Vestibulocerebellar Ataxia Associated with a CACNA1G Missense Variant.
        Case Rep Neurol. 2021; 13 (Published 2021 Jun 11): 347-354
        • Quade A.
        • Thiel A.
        • Kurth I.
        • et al.
        Paroxysmal tonic upgaze: A heterogeneous clinical condition responsive to carbonic anhydrase inhibition.
        Eur J Paediatr Neurol. 2020; 25: 181-186
        • Roubertie A.
        • Echenne B.
        • Leydet J.
        • et al.
        Benign paroxysmal tonic upgaze, benign paroxysmal torticollis, episodic ataxia and CACNA1A mutation in a family.
        J Neurol. 2008; 255: 1600-1602