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Aim: To describe the clinico-radiological phenotype of children with a CACNA1A mutation and to precisely evaluate their learning ability and cognitive status.Method: Children between the ages of 3 and 18 years harboring a pathogenic CACNA1A mutation associated with episodic ataxia, hemiplegic migraine, benign paroxysmal torticollis, benign paroxysmal vertigo, or benign paroxysmal tonic upgaze, were enrolled in this cross-sectional study. Data concerning psychomotor development, academic performance, educational management, clinical examination at inclusion, and brain imaging were collected. Cognitive assessment was performed using age-standardized scales.Results: Eighteen patients (nine males, nine females; mean age at inclusion: 11y 7mo [SD 4y 5mo; range 3y-17y 11mo]) from 14 families were enrolled. Eleven patients displayed the coexistence or consecutive occurrence of more than one type of episodic event. Nine patients exhibited abnormal neurological examination at inclusion. Brain magnetic resonance imaging (MRI) showed cerebellar atrophy in five patients. Psychomotor development was delayed in nine patients and academic difficulties were reported by the parents in 15 patients; nine patients were in special education. Impairment of intellectual function was assessed in six of the 12 patients with interpretable Full-scale IQ scores and was more frequent when cerebellar atrophy was present on MRI.Interpretation: Cognitive impairment is commonly associated with CACNA1A mutations. We suggest that CACNA1A-associated phenotype should be considered a neurodevelopmental disorder.What This Paper Adds: Cognitive disabilities and academic difficulties are common in children with CACNA1A mutations associated with episodic syndromes. Cognitive function ranges from normal to moderate intellectual disorder in wheelchair-dependent children. Patients with vermian atrophy are at a higher risk of cognitive impairment. [ABSTRACT FROM AUTHOR]

Aim: Benign paroxysmal torticollis (BPT), benign paroxysmal vertigo (BPV), and benign tonic upward gaze (BTU) are characterized by transient and recurrent episodes of neurological manifestations. The purpose of this study was to analyse the clinical relationships between these syndromes, associated comorbidities, and genetic bases.Method: In this cross-sectional study, clinical data of patients with BPT, BPV, or BTU were collected with a focus on developmental achievements, learning abilities, and rehabilitation. Neuropsychological assessment and genetic testing were performed.Results: Fifty patients (median age at inclusion 6y) were enrolled. Psychomotor delay, abnormal neurological examination, and low or borderline IQ were found in 19%, 32%, and 26% of the patients respectively. Cognitive dysfunction was present in 27% of the patients. CACNA1A gene mutation was identified in eight families, and KCNA1 and FGF14 mutation in one family respectively. The identification of a CACNA1A mutation was significantly associated with BTU (p=0.03) and with cognitive dysfunction (p=0.01). Patients with BPV were less likely to have cognitive dysfunction.Interpretation: Children with BPT, BPV, or BTU are at high risk of impaired psychomotor and cognitive development. These syndromes should not be regarded as benign and should be considered as part of the spectrum of a neurodevelopmental disorder.What This Paper Adds Ok: Patients with benign paroxysmal torticollis (BPT), benign paroxysmal vertigo (BPV), and benign tonic upward gaze (BTU) have an increased risk of psychomotor delay. These patients also have an increased risk of abnormal neurological examination and cognitive dysfunction. Gene mutations, especially in CACNA1A, were identified in 21% of the families. BPT, BTU, and BPV should not be regarded as benign. BPT, BTU, and BPV should be considered as part of the spectrum of a neurodevelopmental disorder. [ABSTRACT FROM AUTHOR]