Benign paroxysmal tonic upgaze, benign paroxysmal torticollis, episodic ataxia and CACNA1A mutation in a family

Identification of novel and recurrent CACNA1A gene mutations in fifteen patients with episodic ataxia type 2

“…1) confirms the presence of clusters in preferential sites [1,3,4,22,30]. Mantuano et al noted that missense mutations tend to cluster in S5-S6 linkers and their borders, where the mutations of 3 ataxic rodents (tottering mice II S5-S6; rocker mice III S5-S6, groggy rat I S5-S6) are also falling [13,31].…”

“…Less frequent symptoms were epilepsy, weakness, dystonia and mental retardation [8,13,21]. Paroxysmal torticollis has already been found in association with ataxic/vertigo episodes in families with NTR [5] or TR CACNA1A mutations [2][3][4]. Our observation confirm the possibility of this phenotype in association with EA2 mutations and it may be of particular interest especially for paediatricians, who can suspect the diagnosis in the presence of typical episodic neurological symptoms, but also in the presence of uncommon phenotypes including torticollis and hyperhydrosis that may evolve with ageing into EA2 phenotype [22].…”

“…Other neurological features, occurring separately from the episodes of ataxia, are generalized fluctuating weakness, mild permanent cerebellar ataxia, rarely dystonia, and epilepsy. It is to note that benign paroxysmal torticollis of infancy has also been found in association with CACNA1A mutations and ataxic/vertigo episodes [2][3][4][5].…”

Intermittent head drops: the differential spectrum

“…Isolated paroxysmal dyskinesia of the neck, thus resembling IHDs, are quite uncommon except for a condition formerly known as benign paroxysmal torticollis of infancy (BPTI), which has been associated with the CACNA1A 29 and PRRT2 mutation 30 31…”

Ocular Manifestation of CACNA1A Pathogenic Variants

“…This interesting overview of children with heterozygous missense pathogenic variants in the CACNA1A gene gives a new perspective on the disease course. Since the concept of a ‘pre-symptomatic’ eye movement disorder was previously described in children [2, 3] and adults diagnosed with SCA6 [4], the suggestion that all children with PTU, and an ocular motor apraxia or strabismus (especially when associated with developmental delay or cerebellar atrophy), should be considered for CACNA1A genetic testing.…”