#617106
Table of Contents
A number sign (#) is used with this entry because of evidence that developmental and epileptic encephalopathy-42 (DEE42) is caused by heterozygous mutation in the CACNA1A gene (601011) on chromosome 19p13.
Developmental and epileptic encephalopathy-42 (DEE42) is a neurologic disorder characterized by the onset of various types of seizures in the first hours or days of life, although rare patients may have onset in the first weeks of life. The seizures tend to be refractory and associated with EEG abnormalities, including multifocal spikes and generalized spike-wave complexes. Affected infants show global developmental delay with severely impaired intellectual development. Other features may include axial hypotonia, peripheral hypertonia with hyperreflexia, tremor, ataxia, and abnormal eye movements (summary by the Epi4K Consortium, 2016).
For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
The Epi4K Consortium and Epilepsy Phenome/Genome Project (2013) reported a 19-year-old girl (patient EPGP011141) with DEE42. She had onset of myoclonic seizures soon after birth and thereafter showed severe intellectual disability. EEG showed generalized and poly-spike wave discharges and generalized background slowing. Other features included alternating esotropia, nystagmus, ataxic gait, contractures, hypotonia, and autistic features.
The Epi4K Consortium (2016) reported 5 patients, including 2 sibs, with DEE42. The patients had onset of seizures shortly after birth or in the first weeks of life. Seizure types were variable, including focal myoclonic, tonic-clonic, tonic, and convulsive status epilepticus. The patients had delayed global development with moderate to severe intellectual disability. All had an abnormal EEG, with variable manifestations including multifocal discharges, spike-wave discharges, and generalized background slowing. One patient was diagnosed with epilepsy of infancy with migrating focal seizures (EIMFS). Other features included hypotonia, limb hypertonia with hyperreflexia, tremor, ataxic gait, athetosis, and abnormal eye movements. Brain imaging was basically normal.
The heterozygous mutations in the CACNA1A gene that were identified in most patients with DEE42 by the Epi4K Consortium (2016) occurred de novo. However, there was 1 instance of 2 sibs who inherited the mutation from their unaffected mother who was a mosaic carrier.
In 5 patients, including 2 sibs with DEE42, the Epi4K Consortium (2016) identified 4 different heterozygous missense mutations in the CACNA1A gene (see, e.g., 601011.0035-601011.0037). The mutations were found by targeted sequencing of 27 candidate genes in 531 patients with a similar disorder. Functional studies of the variants and studies of patient cells were not performed. The mutations occurred de novo, except in the 2 sibs who inherited the mutation from the unaffected mother who was a mosaic carrier. CACNA1A mutations occurred in 0.8% of the cohort.
Epi4K Consortium and Epilepsy Phenome/Genome Project. De novo mutations in epileptic encephalopathies. Nature 501: 217-221, 2013. [PubMed: 23934111, images, related citations] [Full Text]
Epi4K Consortium. De novo mutations in SLC1A2 and CACNA1A are important causes of epileptic encephalopathies. Am. J. Hum. Genet. 99: 287-298, 2016. [PubMed: 27476654, related citations] [Full Text]
Alternative titles; symbols
ORPHA: 442835; DO: 0080454;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 19p13.13 | Developmental and epileptic encephalopathy 42 | 617106 | Autosomal dominant | 3 | CACNA1A | 601011 |
A number sign (#) is used with this entry because of evidence that developmental and epileptic encephalopathy-42 (DEE42) is caused by heterozygous mutation in the CACNA1A gene (601011) on chromosome 19p13.
Developmental and epileptic encephalopathy-42 (DEE42) is a neurologic disorder characterized by the onset of various types of seizures in the first hours or days of life, although rare patients may have onset in the first weeks of life. The seizures tend to be refractory and associated with EEG abnormalities, including multifocal spikes and generalized spike-wave complexes. Affected infants show global developmental delay with severely impaired intellectual development. Other features may include axial hypotonia, peripheral hypertonia with hyperreflexia, tremor, ataxia, and abnormal eye movements (summary by the Epi4K Consortium, 2016).
For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
The Epi4K Consortium and Epilepsy Phenome/Genome Project (2013) reported a 19-year-old girl (patient EPGP011141) with DEE42. She had onset of myoclonic seizures soon after birth and thereafter showed severe intellectual disability. EEG showed generalized and poly-spike wave discharges and generalized background slowing. Other features included alternating esotropia, nystagmus, ataxic gait, contractures, hypotonia, and autistic features.
The Epi4K Consortium (2016) reported 5 patients, including 2 sibs, with DEE42. The patients had onset of seizures shortly after birth or in the first weeks of life. Seizure types were variable, including focal myoclonic, tonic-clonic, tonic, and convulsive status epilepticus. The patients had delayed global development with moderate to severe intellectual disability. All had an abnormal EEG, with variable manifestations including multifocal discharges, spike-wave discharges, and generalized background slowing. One patient was diagnosed with epilepsy of infancy with migrating focal seizures (EIMFS). Other features included hypotonia, limb hypertonia with hyperreflexia, tremor, ataxic gait, athetosis, and abnormal eye movements. Brain imaging was basically normal.
The heterozygous mutations in the CACNA1A gene that were identified in most patients with DEE42 by the Epi4K Consortium (2016) occurred de novo. However, there was 1 instance of 2 sibs who inherited the mutation from their unaffected mother who was a mosaic carrier.
In 5 patients, including 2 sibs with DEE42, the Epi4K Consortium (2016) identified 4 different heterozygous missense mutations in the CACNA1A gene (see, e.g., 601011.0035-601011.0037). The mutations were found by targeted sequencing of 27 candidate genes in 531 patients with a similar disorder. Functional studies of the variants and studies of patient cells were not performed. The mutations occurred de novo, except in the 2 sibs who inherited the mutation from the unaffected mother who was a mosaic carrier. CACNA1A mutations occurred in 0.8% of the cohort.
Epi4K Consortium and Epilepsy Phenome/Genome Project. De novo mutations in epileptic encephalopathies. Nature 501: 217-221, 2013. [PubMed: 23934111] [Full Text: https://doi.org/10.1038/nature12439]
Epi4K Consortium. De novo mutations in SLC1A2 and CACNA1A are important causes of epileptic encephalopathies. Am. J. Hum. Genet. 99: 287-298, 2016. [PubMed: 27476654] [Full Text: https://doi.org/10.1016/j.ajhg.2016.06.003]
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