RT Journal Article
T1 Clinical phenotypes of infantile onset CACNA1A-related disorder.
A1 Gur-Hartman, Tamar
A1 Berkowitz, Oren
A1 Yosovich, Keren
A1 Roubertie, Agathe
A1 Zanni, Ginevra
A1 Macaya, Alfons
A1 Heimer, Gali
A1 Dueñas, Belén Pérez
A1 Sival, Deborah A
A1 Pode-Shakked, Ben
A1 López-Laso, Eduardo
A1 Humbertclaude, Véronique
A1 Riant, Florence
A1 Bosco, Luca
A1 Cayron, Lital Bachar
A1 Nissenkorn, Andreea
A1 Nicita, Francesco
A1 Bertini, Enrico
A1 Hassin, Sharon
A1 Ben Zeev, Bruria
A1 Zerem, Ayelet
A1 Libzon, Stephanie
A1 Lev, Dorit
A1 Linder, Ilan
A1 Lerman-Sagie, Tally
A1 Blumkin, Lubov
K1 Cognitive difficulties
K1 Congenital cerebellar ataxia
K1 Epilepsy
K1 Episodic ataxia
K1 Paroxysmal disorders
K1 Paroxysmal tonic upward gaze
AB CACNA1A-related disorders present with persistent progressive and non-progressive cerebellar ataxia and paroxysmal events: epileptic seizures and non-epileptic attacks. These phenotypes overlap and co-exist in the majority of patients. To describe phenotypes in infantile onset CACNA1A-related disorder and to explore intra-familial variations and genotype-phenotype correlations. This study was a multicenter international collaboration. A retrospective chart review of CACNA1A patients was performed. Clinical, radiological, and genetic data were collected and analyzed in 47 patients with infantile-onset disorder. Paroxysmal non-epileptic events (PNEE) were observed in 68% of infants, with paroxysmal tonic upward gaze (PTU) noticed in 47% of infants. Congenital cerebellar ataxia (CCA) was diagnosed in 51% of patients including four patients with developmental delay and only one neurological sign. PNEEs were found in 63% of patients at follow-up, with episodic ataxia (EA) in 40% of the sample. Cerebellar ataxia was found in 58% of the patients at follow-up. Four patients had epilepsy in infancy and nine in childhood. Seven infants had febrile convulsions, three of which developed epilepsy later; all three patients had CCA. Cognitive difficulties were demonstrated in 70% of the children. Cerebellar atrophy was found in only one infant but was depicted in 64% of MRIs after age two. Nearly all of the infants had CCA, PNEE or both. Cognitive difficulties were frequent and appeared to be associated with CCA. Epilepsy was more frequent after age two. Febrile convulsions in association with CCA may indicate risk of epilepsy in later childhood. Brain MRI was normal in infancy. There were no genotype-phenotype correlations found.
YR 2020
FD 2020-10-20
LK https://hdl.handle.net/10668/25500
UL https://hdl.handle.net/10668/25500
LA en
DS RISalud
RD Apr 17, 2025