0
selected
-
1.
Heterozygous deletion of SCN2A and SCN3A in a patient with autism spectrum disorder and Tourette syndrome: a case report.
Nickel, K, Tebartz van Elst, L, Domschke, K, Gläser, B, Stock, F, Endres, D, Maier, S, Riedel, A
BMC psychiatry. 2018;(1):248
Abstract
BACKGROUND Mutations in voltage-gated sodium channel (SCN) genes are supposed to be of importance in the etiology of psychiatric and neurological diseases, in particular in the etiology of seizures. Previous studies report a potential susceptibility region at the chromosomal locus 2q including SCN1A, SCN2A and SCN3A genes for autism spectrum disorder (ASD). To date, there is no previous description of a patient with comorbid ASD and Tourette syndrome showing a deletion containing SCN2A and SCN3A. CASE PRESENTATION We present the unique complex case of a 28-year-old male patient suffering from developmental retardation and exhibiting a range of behavioral traits since birth. He received the diagnoses of ASD (in early childhood) and of Tourette syndrome (in adulthood) according to ICD-10 and DSM-5 criteria. Investigations of underlying genetic factors yielded a heterozygous microdeletion of approximately 719 kb at 2q24.3 leading to a deletion encompassing the five genes SCN2A (exon 1 to intron 14-15), SCN3A, GRB14 (exon 1 to intron 2-3), COBLL1 and SCL38A11. CONCLUSIONS We discuss the association of SCN2A, SCN3A, GRB14, COBLL1 and SCL38A11 deletions with ASD and Tourette syndrome and possible implications for treatment.
-
2.
Adults with a history of possible Dravet syndrome: an illustration of the importance of analysis of the SCN1A gene.
Verbeek, NE, van Kempen, M, Gunning, WB, Renier, WO, Westland, B, Lindhout, D, Brilstra, EH
Epilepsia. 2011;(4):e23-5
-
-
Free full text
-
Abstract
Most patients with Dravet syndrome have de novo mutations in the neuronal voltage-gated sodium channel type 1 (SCN1A) gene. We report on two unrelated fathers with severe childhood epilepsy compatible with a possible diagnosis of Dravet syndrome, who both have a child with Dravet syndrome. Analysis of the SCN1A gene revealed a pathogenic mutation in both children. One father exhibited somatic mosaicism for the mutation detected in his son. A relatively favorable cognitive outcome in patients with Dravet syndrome patients may be explained by somatic mosaicism for the SCN1A mutation in brain tissue. A mild form of Dravet syndrome in adult patients is associated with a high recurrence risk and possibly a more severe epilepsy phenotype in their offspring.
-
3.
Progressive neurocognitive decline in two children with Dravet syndrome, de novo SCN1A truncations and different epileptic phenotypes.
Riva, D, Vago, C, Pantaleoni, C, Bulgheroni, S, Mantegazza, M, Franceschetti, S
American journal of medical genetics. Part A. 2009;(10):2339-45
Abstract
Dravet syndrome, often caused by mutations of SCN1A-gene, presents with prolonged clonic, generalized or unilateral seizures often occurring with fever during the first year of life, followed by usually severe epilepsy. The EEG, normal at the outset, later shows generalized and focal epileptic activities. The psychomotor development deteriorates, but little is known about the time course of the cognitive impairment and its relationship with seizures severity. We describe here the progressive neurocognitive decline in two children (one male), carrying de novo SCN1A truncating mutations and presenting with different epileptic phenotypes. The children were longitudinally assessed from the ages of 11 and 23 months until the age of 7 and 8 years, using the same scales to measure the developmental competence in various domains. Both had seizures during the first year of life, unilateral clonic in one and myoclonic in the other, but the subsequent epilepsy severity and the characteristics of the EEG diverged. One child had drug-resistant but rare generalized seizures and isolated EEG spike-wave paroxysms, while the other developed extremely frequent clusters of polymorphic seizures and generalized plus multifocal EEG epileptic activities. MRI was normal in both. A clear developmental delay begun before the age of 2 years in both children and the cognitive profile continued to worse, with some differences between different domains, irrespectively to the different course of their epileptic histories. Our observations are consistent with the hypothesis that SCN1A-mutations can be responsible not only for epilepsy, but also for early and progressive severe mental impairment.
-
4.
Elicited repetitive daily blindness: a new phenotype associated with hemiplegic migraine and SCN1A mutations.
Vahedi, K, Depienne, C, Le Fort, D, Riant, F, Chaine, P, Trouillard, O, Gaudric, A, Morris, MA, Leguern, E, Tournier-Lasserve, E, et al
Neurology. 2009;(13):1178-83
Abstract
OBJECTIVE Familial hemiplegic migraine (FHM) is a genetically heterogeneous disorder in which three genes, CACNA1A, ATP1A2, and SCN1A, are currently known to be involved. FHM is occasionally associated with other neurologic symptoms such as cerebellar ataxia or epileptic seizures. A unique eye phenotype of elicited repetitive daily blindness (ERDB) has also been reported to be cosegregating with FHM in a single Swiss family. METHODS We report an additional family in whom the proband had, in addition to FHM, typical ERDB. In this family and the previously reported Swiss family, the whole coding region of the SCN1A gene was screened after exclusion of mutation in CACNA1A and ATP1A2 genes. RESULTS We identified two novel SCN1A mutations (c.4495T>C/p.Phe1499Leu and c.4467G>C/p.Gln1489His missense substitutions) in exons 24 and 23, respectively, segregating with the disease in all living affected members. Both mutations were absent from 180 healthy Caucasian controls and were located in an intracellular loop highly conserved throughout evolution. CONCLUSION We report new clinical data supporting cosegregation of familial hemiplegic migraine and the new eye phenotype of elicited repetitive daily blindness and two novel SCN1A mutations as the underlying genetic defect in two unrelated families. SCN1A encodes the voltage-gated sodium channel Nav1.1 that is highly expressed in the CNS including the retina. This remarkably stereotyped new eye phenotype has clinical characteristics of abnormal propagation of the retinal electrical signal that may be a retinal spreading depression. These results suggest that SCN1A mutations, which alter neuronal brain excitability, may occasionally alter retinal cell excitability.
-
5.
Severe myoclonic epilepsy in infancy: clinical analysis and relation to SCN1A mutations in a Japanese cohort.
Oguni, H, Hayashi, K, Osawa, M, Awaya, Y, Fukuyama, Y, Fukuma, G, Hirose, S, Mitsudome, A, Kaneko, S
Advances in neurology. 2005;:103-17
-
6.
Severe infantile hyperkalaemic periodic paralysis and paramyotonia congenita: broadening the clinical spectrum associated with the T704M mutation in SCN4A.
Brancati, F, Valente, EM, Davies, NP, Sarkozy, A, Sweeney, MG, LoMonaco, M, Pizzuti, A, Hanna, MG, Dallapiccola, B
Journal of neurology, neurosurgery, and psychiatry. 2003;(9):1339-41
-
-
Free full text
-
Abstract
The authors describe an Italian kindred with nine individuals affected by hyperkalaemic periodic paralysis associated with paramyotonia congenita (hyperPP/PMC). Periodic paralysis was particularly severe, with several episodes a day lasting for hours. The onset of episodes was unusually early, beginning in the first year of life and persisting into adult life. The paralytic episodes were refractory to treatment. Patients described minimal paramyotonia, mainly of the eyelids and hands. All affected family members carried the threonine to methionine substitution at codon 704 (T704M) in exon 13 of the skeletal muscle voltage gated sodium channel gene (SCN4A). The association between T704M and the hyperPP/PMC phenotype has been only recently revealed. Nevertheless, such a severe phenotype has never been reported so far in families with either hyperPP or hyperPP/PMC. These data further broaden the clinical spectrum of T704M and support the evidence that this mutation is a common cause of hyperPP/PMC.