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Early infantile epileptic encephalopathy 13(EIEE13)

MedGen UID:
482821
Concept ID:
C3281191
Disease or Syndrome
Synonyms: EIEE13; SCN8A-Related Epilepsy
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
 
Gene (location): SCN8A (12q13.13)
OMIM®: 614558

Disease characteristics

Excerpted from the GeneReview: SCN8A-Related Epilepsy with Encephalopathy
SCN8A-related epilepsy with encephalopathy is characterized by developmental delay, seizure onset in the first 18 months of life (mean 4 months), and intractable epilepsy characterized by multiple seizure types (generalized tonic-clonic seizures, infantile spasms, and absence and focal seizures). Epilepsy syndromes can include Lennox-Gastaut syndrome, West syndrome, and epileptic encephalopathies (e.g., Dravet syndrome). Hypotonia and movement disorders including dystonia, ataxia, and choreoathetosis are common. Psychomotor development varies from normal prior to seizure onset (with subsequent slowing or regression after seizure onset) to abnormal from birth. Intellectual disability, present in all, ranges from mild to severe (in ~50% of affected individuals). Autistic features are noted in some. Sudden unexpected death in epilepsy (SUDEP) of unknown cause has been reported in approximately 10% of published cases. To date SCN8A-related epilepsy with encephalopathy has been reported in the literature in about 50 individuals. [from GeneReviews]
Authors:
Michael F Hammer  |  Jacy L Wagnon  |  Heather C Mefford, et. al.   view full author information

Clinical features

Autistic disorder of childhood onset
MedGen UID:
13966
Concept ID:
C0004352
Mental or Behavioral Dysfunction
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). Levy et al. (2009) provided a general review of autism and autism spectrum disorder, including epidemiology, characteristics of the disorder, diagnosis, neurobiologic hypotheses for the etiology, genetics, and treatment options. Genetic Heterogeneity of Autism Autism is considered to be a complex multifactorial disorder involving many genes. Accordingly, several loci have been identified, some or all of which may contribute to the phenotype. Included in this entry is AUTS1, which has been mapped to chromosome 7q22. Other susceptibility loci include AUTS3 (608049), which maps to chromosome 13q14; AUTS4 (608636), which maps to chromosome 15q11; AUTS5 (606053), which maps to chromosome 2q; AUTS6 (609378), which maps to chromosome 17q11; AUTS7 (610676), which maps to chromosome 17q21; AUTS8 (607373), which maps to chromosome 3q25-q27; AUTS9 (611015), which maps to chromosome 7q31; AUTS10 (611016), which maps to chromosome 7q36; AUTS11 (610836), which maps to chromosome 1q41; AUTS12 (610838), which maps to chromosome 21p13-q11; AUTS13 (610908), which maps to chromosome 12q14; AUTS14A (611913), which has been found in patients with a deletion of a region of 16p11.2; AUTS14B (614671), which has been found in patients with a duplication of a region of 16p11.2; AUTS15 (612100), associated with mutation in the CNTNAP2 gene (604569) on chromosome 7q35-q36; AUTS16 (613410), associated with mutation in the SLC9A9 gene (608396) on chromosome 3q24; AUTS17 (613436), associated with mutation in the SHANK2 gene (603290) on chromosome 11q13; and AUTS18 (615032), associated with mutation in the CHD8 gene (610528). (NOTE: the symbol 'AUTS2' has been used to refer to a gene on chromosome 7q11 (KIAA0442; 607270) and therefore is not used as a part of this autism locus series.) There are several X-linked forms of autism susceptibility: AUTSX1 (300425), associated with mutations in the NLGN3 gene (300336); AUTSX2 (300495), associated with mutations in NLGN4 (300427); AUTSX3 (300496), associated with mutations in MECP2 (300005); AUTSX4 (300830), associated with variation in the region on chromosome Xp22.11 containing the PTCHD1 gene (300828); AUTSX5 (300847), associated with mutations in the RPL10 gene (312173); and AUTSX6 (300872), associated with mutation in the TMLHE gene (300777). Folstein and Rosen-Sheidley (2001) reviewed the genetics of autism.
Cerebral degeneration
MedGen UID:
56343
Concept ID:
C0154671
Disease or Syndrome
Partial or complete wasting (loss) of brain tissue that was once present.
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
Epileptic encephalopathy
MedGen UID:
452596
Concept ID:
C0543888
Disease or Syndrome
Epileptic spasms
MedGen UID:
315948
Concept ID:
C1527366
Disease or Syndrome
A sudden flexion, extension or mixed extension-flexion of predominantly proximal and truncal muscles which is usually more sustained than a myoclonic movement but not as sustained as a tonic seizure.
Progressive microcephaly
MedGen UID:
340542
Concept ID:
C1850456
Finding
Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms.
Psychomotor regression, progressive
MedGen UID:
340556
Concept ID:
C1850493
Finding
Loss of developmental skills, as manifested by loss of developmental milestones.
Cognitive delay
MedGen UID:
351243
Concept ID:
C1864897
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28)
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Muscular hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is characterized by a diminished resistance to passive stretching.
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
Progressive microcephaly
MedGen UID:
340542
Concept ID:
C1850456
Finding
Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms.
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
Progressive microcephaly
MedGen UID:
340542
Concept ID:
C1850456
Finding
Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms.

Recent clinical studies

Etiology

Zhang Q, Li J, Zhao Y, Bao X, Wei L, Wang J
Clin Genet 2017 May;91(5):717-724. Epub 2017 Feb 16 doi: 10.1111/cge.12901. PMID: 27779742
Li PH, Chi CS, Mak SC, Chen CH, Yang MT
Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi 1997 May-Jun;38(3):203-7. PMID: 9230537
Ohtahara S, Ohtsuka Y, Yamatogi Y, Oka E, Yoshinaga H, Sato M
Epilepsia 1993 Jul-Aug;34(4):716-22. PMID: 8330583

Diagnosis

Weeke LC, Brilstra E, Braun KP, Zonneveld-Huijssoon E, Salomons GS, Koeleman BP, van Gassen KL, van Straaten HL, Craiu D, de Vries LS
Eur J Paediatr Neurol 2017 Mar;21(2):396-403. Epub 2016 Nov 19 doi: 10.1016/j.ejpn.2016.11.002. PMID: 27913086
Zhang Q, Li J, Zhao Y, Bao X, Wei L, Wang J
Clin Genet 2017 May;91(5):717-724. Epub 2017 Feb 16 doi: 10.1111/cge.12901. PMID: 27779742
Blanchard MG, Willemsen MH, Walker JB, Dib-Hajj SD, Waxman SG, Jongmans MC, Kleefstra T, van de Warrenburg BP, Praamstra P, Nicolai J, Yntema HG, Bindels RJ, Meisler MH, Kamsteeg EJ
J Med Genet 2015 May;52(5):330-7. Epub 2015 Feb 27 doi: 10.1136/jmedgenet-2014-102813. PMID: 25725044Free PMC Article
Matsumoto H, Zaha K, Nakamura Y, Hayashi S, Inazawa J, Nonoyama S
Pediatr Neurol 2014 Jul;51(1):170-5. Epub 2014 Apr 4 doi: 10.1016/j.pediatrneurol.2014.03.013. PMID: 24938147
Yamatogi Y, Ohtahara S
Brain Dev 2002 Jan;24(1):13-23. PMID: 11751020

Therapy

Zhang Q, Li J, Zhao Y, Bao X, Wei L, Wang J
Clin Genet 2017 May;91(5):717-724. Epub 2017 Feb 16 doi: 10.1111/cge.12901. PMID: 27779742
Ohtahara S, Ohtsuka Y, Yamatogi Y, Oka E, Yoshinaga H, Sato M
Epilepsia 1993 Jul-Aug;34(4):716-22. PMID: 8330583

Prognosis

Mignot C, Lambert L, Pasquier L, Bienvenu T, Delahaye-Duriez A, Keren B, Lefranc J, Saunier A, Allou L, Roth V, Valduga M, Moustaïne A, Auvin S, Barrey C, Chantot-Bastaraud S, Lebrun N, Moutard ML, Nougues MC, Vermersch AI, Héron B, Pipiras E, Héron D, Olivier-Faivre L, Guéant JL, Jonveaux P, Philippe C
J Med Genet 2015 Jan;52(1):61-70. Epub 2014 Nov 19 doi: 10.1136/jmedgenet-2014-102748. PMID: 25411445
Ohtahara S, Ohtsuka Y, Yamatogi Y, Oka E, Yoshinaga H, Sato M
Epilepsia 1993 Jul-Aug;34(4):716-22. PMID: 8330583

Clinical prediction guides

Weeke LC, Brilstra E, Braun KP, Zonneveld-Huijssoon E, Salomons GS, Koeleman BP, van Gassen KL, van Straaten HL, Craiu D, de Vries LS
Eur J Paediatr Neurol 2017 Mar;21(2):396-403. Epub 2016 Nov 19 doi: 10.1016/j.ejpn.2016.11.002. PMID: 27913086
Zhang Q, Li J, Zhao Y, Bao X, Wei L, Wang J
Clin Genet 2017 May;91(5):717-724. Epub 2017 Feb 16 doi: 10.1111/cge.12901. PMID: 27779742
Mignot C, Lambert L, Pasquier L, Bienvenu T, Delahaye-Duriez A, Keren B, Lefranc J, Saunier A, Allou L, Roth V, Valduga M, Moustaïne A, Auvin S, Barrey C, Chantot-Bastaraud S, Lebrun N, Moutard ML, Nougues MC, Vermersch AI, Héron B, Pipiras E, Héron D, Olivier-Faivre L, Guéant JL, Jonveaux P, Philippe C
J Med Genet 2015 Jan;52(1):61-70. Epub 2014 Nov 19 doi: 10.1136/jmedgenet-2014-102748. PMID: 25411445
Yamatogi Y, Ohtahara S
Brain Dev 2002 Jan;24(1):13-23. PMID: 11751020
Ohtahara S, Ohtsuka Y, Yamatogi Y, Oka E, Yoshinaga H, Sato M
Epilepsia 1993 Jul-Aug;34(4):716-22. PMID: 8330583

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