The neuropsychiatric phenotype in <i>CACNA1A</i> mutations: a retrospective single center study and review of the literature

Indelicato, Elisabetta; Nachbauer, Wolfgang; Karner, Elfriede; Eigentler, Andreas; Wagner, M.; Unterberger, Iris; Poewe, Werner; Delazer, Margarete; Boesch, Sylvia

doi:10.1111/ene.13765

Cited by 36 publications

(34 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recently, a large case series of 23/44 patients (11/23 FHM1,10/23 EA2, 2/23 SCA6), investigated by a formal neuropsychological testing, predominantly showed figural memory, visuoconstructive abilities, and verbal fluency impairment. Furthermore, the study revealed that neuropsychological deficits were consistent with history of development delay of patients [19]. A case study carried out using a formal neuropsychological assessment reported an impairment of semantic fluency and of processing speed, and a mild executive dysfunction [18].…”

Section: Discussionmentioning

confidence: 57%

“…This co-occurrence in CACNA1A mutant patients has been associated with more severe outcome [16]. Many studies remarked in FHM1, EA2,and SCA6 patients the co-occurrence of behavioral and neuropsychological disorders but the investigations carried out with formal neuropsychological testing are scarce [17][18][19]. Recently, a large case series of 23/44 patients (11/23 FHM1,10/23 EA2, 2/23 SCA6), investigated by a formal neuropsychological testing, predominantly showed figural memory, visuoconstructive abilities, and verbal fluency impairment.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Two distinct phenotypes, hemiplegic migraine and episodic Ataxia type 2, caused by a novel common CACNA1A variant

et al. 2020

View full text Add to dashboard Cite

Background: To investigate the genetic and environmental factors responsible for phenotype variability in a family carrying a novel CACNA1A missense mutation. Mutations in the CACNA1A gene were identified as responsible for at least three autosomal dominant disorders: FHM1 (Familial Hemiplegic Migraine), EA2 (Episodic Ataxia type 2), and SCA6 (Spinocerebellar Ataxia type 6). Overlapping clinical features within individuals of some families sharing the same CACNA1A mutation are not infrequent. Conversely, reports with distinct phenotypes within the same family associated with a common CACNA1A mutation are very rare. Case presentation: A clinical, molecular, neuroradiological, neuropsychological, and neurophysiological study was carried out in proband and his carrier mother. The new heterozygous missense variant c.4262G > A (p.Arg1421Gln) in the CACNA1A gene was detected in the two affected family members. The proband showed a complex clinical presentation characterized by developmental delay, poor motor coordination, hemiplegic migraine attacks, behavioral dysregulation, and EEG abnormalities. The mother showed typical episodic ataxia attacks during infancy with no other comorbidities and mild cerebellar signs at present neurological evaluation. Conclusions: The proband and his mother exhibit two distinct clinical phenotypes. It can be hypothesized that other unknown modifying genes and/or environmental factors may cooperate to generate the wide intrafamilial variability.

show abstract

Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Two distinct phenotypes, hemiplegic migraine and episodic Ataxia type 2, caused by a novel common CACNA1A variant

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Precise cognitive evaluations are the main contribution of our study. Recently, Indelicato et al . reported cognitive and behavioral features in a series of patients with CACNA1A mutations.…”

Section: Discussionmentioning

confidence: 99%

“…Precise cognitive evaluations are the main contribution of our study. Recently, Indelicato et al 23 reported cognitive and behavioral features in a series of patients with CACNA1A mutations. However, the authors performed a retrospective analysis of data extracted from a database initially developed for another objective, therefore the protocol assessment of cognitive function was not uniform.…”

Section: Discussionmentioning

confidence: 99%

“…6,[11][12][13][14][15][16] Among the chronic neurological manifestations associated with heterozygous CACNA1A mutations, cognitive dysfunction has been suggested in recent years, including developmental delay, learning difficulties, autism, attention-deficit/hyperactivity disorder, intellectual impairment, and epileptic or non-epileptic encephalopathy. 6,[17][18][19][20][21][22][23] Until now, the cognitive profile of children with CACNA1A mutations has not been studied systematically in a series of patients.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Cognitive impairment in children with CACNA1A mutations

Humbertclaude

Riant

Krams

et al. 2019

Develop Med Child Neuro

View full text Add to dashboard Cite

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.

show abstract

When rare meets common: Treatable genetic diseases are enriched in the general psychiatric population

Sriretnakumar,

Harripaul,

Kennedy

et al. 2024

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Mental illnesses are one of the biggest contributors to the global disease burden. Despite the increased recognition, diagnosis and ongoing research of mental health disorders, the etiology and underlying molecular mechanisms of these disorders are yet to be fully elucidated. Moreover, despite many treatment options available, a large subset of the psychiatric patient population is nonresponsive to standard medications and therapies. There has not been a comprehensive study to date examining the burden and impact of treatable genetic disorders (TGDs) that can present with neuropsychiatric features in psychiatric patient populations. In this study, we test the hypothesis that TGDs that present with psychiatric symptoms are more prevalent within psychiatric patient populations compared to the general population by performing targeted next‐generation sequencing of 129 genes associated with 108 TGDs in a cohort of 2301 psychiatric patients. In total, 48 putative affected and 180 putative carriers for TGDs were identified, with known or likely pathogenic variants in 79 genes. Despite screening for only 108 genetic disorders, this study showed a two‐fold (2.09%) enrichment for genetic disorders within the psychiatric population relative to the estimated 1% cumulative prevalence of all single gene disorders globally. This strongly suggests that the prevalence of these, and most likely all, genetic diseases is greatly underestimated in psychiatric populations. Increasing awareness and ensuring accurate diagnosis of TGDs will open new avenues to targeted treatment for a subset of psychiatric patients.

show abstract

The neuropsychiatric phenotype in CACNA1A mutations: a retrospective single center study and review of the literature

Abstract: Neuropsychiatric manifestations are common in episodic CACNA1A disorders. In the case of otherwise unexplained developmental delay and a positive family history, CACNA1A mutations should be considered in the differential diagnosis.

Cited by 36 publications

References 73 publications

Two distinct phenotypes, hemiplegic migraine and episodic Ataxia type 2, caused by a novel common CACNA1A variant

Two distinct phenotypes, hemiplegic migraine and episodic Ataxia type 2, caused by a novel common CACNA1A variant

Cognitive impairment in children with CACNA1A mutations

When rare meets common: Treatable genetic diseases are enriched in the general psychiatric population

Contact Info

Product

Resources

About