ORPHA:442835

Non-specific early-onset epileptic encephalopathy

Synonyms: Non-specific EOEE · Undetermined EOEE · Undetermined early-onset epileptic encephalopathy

Type: Disease
Group: Disorder
Inheritance: Autosomal dominant, Autosomal recessive, Not applicable, X-linked recessive
Age of onset: Infancy, Neonatal
Status: active

A rare infantile epilepsy syndrome characterized by early onset of seizures of variable type and severity, potentially associated with a spectrum of clinical signs and symptoms including delay or lack of psychomotor development, intellectual disability, poor or absent speech development, behavioral abnormalities, hypotonia, movement disorders, spasticity, microcephaly, and dysmorphic facial features, among others. Brain imaging findings are also variable and may include cerebral atrophy or white matter abnormalities.

Names in Orphadata languages

12 of 12 languages

Lang	Name	Synonyms
en	Non-specific early-onset epileptic encephalopathy	Non-specific EOEE · Undetermined EOEE · Undetermined early-onset epileptic encephalopathy
fr	Encéphalopathie épileptique à début précoce non spécifique	Encéphalopathie épileptique à début précoce indéterminée
de	Enzephalopathie, epileptische, frühinfantile unbestimmte Form	Unbestimmte EOEE
es	Encefalopatía epiléptica inespecífica de inicio precoz	EOEE indeterminada · EOEE inespecífica · Encefalopatía epiléptica indeterminada de inicio precoz
it	Encefalopatia epilettica indeterminata ad esordio precoce	EOEE generica · EOEE non specificata · Encefalopatia epilettica generica ad esordio precoce
nl	Aspecifieke epileptische encefalopathie met vroege aanvang	Aspecifieke EOEE · Onbepaalde EOEE · Onbepaalde vroeg optredende epileptische encefalopathie
pt	Encefalopatia epilética de início precoce inespecífica	Encefalopatia epilética de causa indeterminada e início precoce
pl	Niezdeterminowana encefalopatia padaczkowa o wczesnym początku	Niezdeterminowana EOEE
cs	Neurčená epileptická encefalopatie s časným nástupem	Neurčená EOEE
uk	Неспецифічна рання епілептична енцефалопатія	Неспецифічні ЕОЕЕ · Невизначена епілептична енцефалопатія з раннім початком · Невизначений ЕОЕЕ
zh	未确定的早发性癫痫性脑病	未确定EOEE
tr	Belirsiz, erken başlangıçlı epileptik ensefalopati	Belirlenmemiş EOEE

Definition in:

Cross-references

qualifier = Orphanet mapping relation

Source	Code	Qualifier	ICD relation	Validation
OMIM	301058	BTNT		validated
OMIM	614558	BTNT		validated
OMIM	615476	BTNT		validated
OMIM	615833	BTNT		validated
OMIM	615871	BTNT		validated
OMIM	615905	BTNT		validated
OMIM	616056	BTNT		validated
OMIM	616339	BTNT		validated
OMIM	616346	BTNT		validated
OMIM	616366	BTNT		validated
OMIM	616409	BTNT		validated
OMIM	617020	BTNT		validated
OMIM	617105	BTNT		validated
OMIM	617106	BTNT		validated
OMIM	617132	BTNT		validated
OMIM	617153	BTNT		validated
OMIM	617162	BTNT		validated
OMIM	617166	BTNT		validated
OMIM	617665	BTNT		validated
OMIM	617711	BTNT		validated
OMIM	617771	BTNT		validated
OMIM	617829	BTNT		validated
OMIM	617830	BTNT		validated
OMIM	617831	BTNT		validated
OMIM	617836	BTNT		validated
OMIM	617854	BTNT		validated
OMIM	617938	BTNT		validated
OMIM	618008	BTNT		validated
OMIM	618012	BTNT		validated
OMIM	618067	NTBT		validated
OMIM	618201	BTNT		validated
OMIM	618396	BTNT		validated
OMIM	618437	BTNT		validated
OMIM	618468	BTNT		validated
OMIM	618497	BTNT		validated
OMIM	618557	BTNT		validated
OMIM	618559	BTNT		validated
OMIM	618910	BTNT		validated
OMIM	618916	BTNT		validated
OMIM	618959	BTNT		validated
OMIM	619124	BTNT		validated
OMIM	619317	BTNT		validated
OMIM	619561	BTNT		validated
OMIM	619605	BTNT		validated
OMIM	619606	BTNT		validated
OMIM	619777	BTNT		validated
OMIM	619814	BTNT		validated
OMIM	619881	BTNT		validated
OMIM	619913	BTNT		validated
OMIM	619922	BTNT		validated
OMIM	619970	BTNT		validated
OMIM	620028	BTNT		validated
OMIM	620033	BTNT		validated
OMIM	620115	BTNT		validated
OMIM	620145	BTNT		validated
OMIM	620149	BTNT		validated
OMIM	620352	BTNT		validated
OMIM	620504	BTNT		validated
OMIM	620537	BTNT		validated
OMIM	621608	BTNT		validated
ICD-10	G40.4	NTBT	attributed	validated
MONDO	0018614	E		validated
UMLS	C5680057	E		validated

E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.

Classification

Preferential parent (Orphanet linearisation):

ORPHA:98006Rare neurologic disease

Parents in the classifications (6):

ORPHA:166472Monogenic disease with epilepsy
rare genetic diseases; rare neurological diseases
ORPHA:98749Neurological channelopathy of the central nervous system due to a genetic GABA receptor defect
rare genetic diseases
ORPHA:98745Neurological channelopathy of the central nervous system due to a genetic calcium channel defect
rare genetic diseases
ORPHA:98746Neurological channelopathy of the central nervous system due to a genetic potassium channel defect
rare genetic diseases
ORPHA:98744Neurological channelopathy of the central nervous system due to a genetic sodium channel defect
rare genetic diseases
ORPHA:611314Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome
rare genetic diseases; rare neurological diseases

No children.

Codes that Orphanet moved or referred to this one:

ORPHA:369894OBSOLETE: Early infantile epileptic encephalopathy without suppression burst referred to · inactive

Genes

55 direct

Gene	Association	Status	HGNC	Ensembl	OMIM	Locus	Name	Source of validation
SYNGAP1	Candidate gene tested in	Not yet assessed	HGNC:11497	ENSG00000197283	603384	6p21.32	synaptic Ras GTPase activating protein 1	23708187[PMID]
FGF12	Disease-causing germline mutation(s) (gain of function) in	Assessed	HGNC:3668	ENSG00000114279	601513	3q28-q29	fibroblast growth factor 12	27164707[PMID]
GRIN2D	Disease-causing germline mutation(s) (gain of function) in	Assessed	HGNC:4588	ENSG00000105464	602717	19q13.33	glutamate ionotropic receptor NMDA type subunit 2D	27616483[PMID]
HCN1	Disease-causing germline mutation(s) (gain of function) in	Assessed	HGNC:4845	ENSG00000164588	602780	5p12	hyperpolarization activated cyclic nucleotide gated potassium channel 1	24747641[PMID]_25678871[PMID]
KCNA2	Disease-causing germline mutation(s) (gain of function) in	Assessed	HGNC:6220	ENSG00000177301	176262	1p13.3	potassium voltage-gated channel subfamily A member 2	25751627[PMID]
SCN8A	Disease-causing germline mutation(s) (gain of function) in	Assessed	HGNC:10596	ENSG00000196876	600702	12q13.13	sodium voltage-gated channel alpha subunit 8	22365152[PMID]_23708187[PMID]
AARS1	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:20	ENSG00000090861	601065	16q22.1	alanyl-tRNA synthetase 1	25817015[PMID]
CACNA1B	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:1389	ENSG00000148408	601012	9q34.3	calcium voltage-gated channel subunit alpha1 B	30982612[PMID]
DALRD3	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:25536	ENSG00000178149	618904	3p21.31	DALR anticodon binding domain containing 3	32427860[PMID]
KCNA2	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:6220	ENSG00000177301	176262	1p13.3	potassium voltage-gated channel subfamily A member 2	25751627[PMID]
KCNC2	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:6234	ENSG00000166006	176256	12q21.1	potassium voltage-gated channel subfamily C member 2	35314505[PMID]
NECAP1	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:24539	ENSG00000089818	611623	12p13.31	NECAP endocytosis associated 1	24399846[PMID]
TRAK1	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:29947	ENSG00000182606	608112	3p22.1	trafficking kinesin protein 1	28364549[PMID]
UBA5	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:23230	ENSG00000081307	610552	3q22.1	ubiquitin like modifier activating enzyme 5	27545674[PMID]_27545681[PMID]
UFSP2	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:25640	ENSG00000109775	611482	4q35.1	UFM1 specific peptidase 2	33473208[PMID]
ACTL6B	Disease-causing germline mutation(s) in	Assessed	HGNC:160	ENSG00000077080	612458	7q22.1	actin like 6B	31031012[PMID]
AP3B2	Disease-causing germline mutation(s) in	Assessed	HGNC:567	ENSG00000103723	602166	15q25.2	adaptor related protein complex 3 subunit beta 2	27889060[PMID]
ATP1A2	Disease-causing germline mutation(s) in	Assessed	HGNC:800	ENSG00000018625	182340	1q23.2	ATPase Na+/K+ transporting subunit alpha 2	33880529[PMID]
ATP1A3	Disease-causing germline mutation(s) in	Assessed	HGNC:801	ENSG00000105409	182350	19q13.2	ATPase Na+/K+ transporting subunit alpha 3	33880529[PMID]
ATP6V1A	Disease-causing germline mutation(s) in	Assessed	HGNC:851	ENSG00000114573	607027	3q13.31	ATPase H+ transporting V1 subunit A	29668857[PMID]
CACNA1A	Disease-causing germline mutation(s) in	Assessed	HGNC:1388	ENSG00000141837	601011	19p13.13	calcium voltage-gated channel subunit alpha1 A	27476654[PMID]
CACNA2D1	Disease-causing germline mutation(s) in	Assessed	HGNC:1399	ENSG00000153956	114204	7q21.11	calcium voltage-gated channel auxiliary subunit alpha2delta 1	35293990[PMID]
CDK19	Disease-causing germline mutation(s) in	Assessed	HGNC:19338	ENSG00000155111	614720	6q21	cyclin dependent kinase 19	32330417[PMID]
CELF2	Disease-causing germline mutation(s) in	Assessed	HGNC:2550	ENSG00000048740	602538	10p14	CUGBP Elav-like family member 2	33131106[PMID]
CLTC	Disease-causing germline mutation(s) in	Assessed	HGNC:2092	ENSG00000141367	118955	17q23.1	clathrin heavy chain	29100083[PMID]
CNKSR2	Disease-causing germline mutation(s) in	Assessed	HGNC:19701	ENSG00000149970	300724	Xp22.12	connector enhancer of kinase suppressor of Ras 2	25223753[PMID]
CYFIP2	Disease-causing germline mutation(s) in	Assessed	HGNC:13760	ENSG00000055163	606323	5q33.3	cytoplasmic FMR1 interacting protein 2	29534297[PMID]
DEPDC5	Disease-causing germline mutation(s) in	Assessed	HGNC:18423	ENSG00000100150	614191	22q12.2-q12.3	DEP domain containing 5, GATOR1 subcomplex subunit	36067010[PMID]
DHDDS	Disease-causing germline mutation(s) in	Assessed	HGNC:20603	ENSG00000117682	608172	1p36.11	dehydrodolichyl diphosphate synthase subunit	29100083[PMID]
DNM1	Disease-causing germline mutation(s) in	Assessed	HGNC:2972	ENSG00000106976	602377	9q34.11	dynamin 1	25262651[PMID]_25533962[PMID]
EEF1A2	Disease-causing germline mutation(s) in	Assessed	HGNC:3192	ENSG00000101210	602959	20q13.33	eukaryotic translation elongation factor 1 alpha 2	23647072[PMID]
FBXO28	Disease-causing germline mutation(s) in	Assessed	HGNC:29046	ENSG00000143756	609100	1q42.11	F-box protein 28	33280099[PMID]
FOXG1	Disease-causing germline mutation(s) in	Assessed	HGNC:3811	ENSG00000176165	164874	14q12	forkhead box G1	31454984[PMID]
FZR1	Disease-causing germline mutation(s) in	Assessed	HGNC:24824	ENSG00000105325	603619	19p13.3	fizzy and cell division cycle 20 related 1	34788397[PMID]
GABBR2	Disease-causing germline mutation(s) in	Assessed	HGNC:4507	ENSG00000136928	607340	9q22.33	gamma-aminobutyric acid type B receptor subunit 2	25262651[PMID]
GABRA2	Disease-causing germline mutation(s) in	Assessed	HGNC:4076	ENSG00000151834	137140	4p12	gamma-aminobutyric acid type A receptor subunit alpha2	31032849[PMID]
GABRA5	Disease-causing germline mutation(s) in	Assessed	HGNC:4079	ENSG00000186297	137142	15q12	gamma-aminobutyric acid type A receptor subunit alpha5	31056671[PMID]
GABRB2	Disease-causing germline mutation(s) in	Assessed	HGNC:4082	ENSG00000145864	600232	5q34	gamma-aminobutyric acid type A receptor subunit beta2	29100083[PMID]
GABRG2	Disease-causing germline mutation(s) in	Assessed	HGNC:4087	ENSG00000113327	137164	5q34	gamma-aminobutyric acid type A receptor subunit gamma2	27864268[PMID]
KCNB1	Disease-causing germline mutation(s) in	Assessed	HGNC:6231	ENSG00000158445	600397	20q13.13	potassium voltage-gated channel subfamily B member 1	25164438[PMID]
KCNH5	Disease-causing germline mutation(s) in	Assessed	HGNC:6254	ENSG00000140015	605716	14q23.2	potassium voltage-gated channel subfamily H member 5	36307226[PMID]
MDGA2	Disease-causing germline mutation(s) in	Assessed	HGNC:19835			14q21.3	MAM domain containing glycosylphosphatidylinositol anchor 2	41570816[PMID]
NTRK2	Disease-causing germline mutation(s) in	Assessed	HGNC:8032	ENSG00000148053	600456	9q21.33	neurotrophic receptor tyrosine kinase 2	29100083[PMID]
NUS1	Disease-causing germline mutation(s) in	Assessed	HGNC:21042	ENSG00000153989	610463	6q22.1	NUS1 dehydrodolichyl diphosphate synthase subunit	29100083[PMID]
PACS2	Disease-causing germline mutation(s) in	Assessed	HGNC:23794	ENSG00000179364	610423	14q32.33	phosphofurin acidic cluster sorting protein 2	29656858[PMID]
PARS2	Disease-causing germline mutation(s) in	Assessed	HGNC:30563	ENSG00000162396	612036	1p32.3	prolyl-tRNA synthetase 2, mitochondrial	29915213[PMID]
PPP3CA	Disease-causing germline mutation(s) in	Assessed	HGNC:9314	ENSG00000138814	114105	4q24	protein phosphatase 3 catalytic subunit alpha	28942967[PMID]
SCN1A	Disease-causing germline mutation(s) in	Assessed	HGNC:10585	ENSG00000144285	182389	2q24.3	sodium voltage-gated channel alpha subunit 1	24776920[PMID]
SCN3A	Disease-causing germline mutation(s) in	Assessed	HGNC:10590	ENSG00000153253	182391	2q24.3	sodium voltage-gated channel alpha subunit 3	29466837[PMID]
SLC13A5	Disease-causing germline mutation(s) in	Assessed	HGNC:23089	ENSG00000141485	608305	17p13.1	solute carrier family 13 member 5	24995870[PMID]
SLC1A2	Disease-causing germline mutation(s) in	Assessed	HGNC:10940	ENSG00000110436	600300	11p13	solute carrier family 1 member 2	27476654[PMID]_28777935[PMID]
SLC38A3	Disease-causing germline mutation(s) in	Assessed	HGNC:18044	ENSG00000188338	604437	3p21.31	solute carrier family 38 member 3	34605855[PMID]
SYNJ1	Disease-causing germline mutation(s) in	Assessed	HGNC:11503	ENSG00000159082	604297	21q22.11	synaptojanin 1	27435091[PMID]
SZT2	Disease-causing germline mutation(s) in	Assessed	HGNC:29040	ENSG00000198198	615463	1p34.2	SZT2 subunit of KICSTOR complex	23932106[PMID]
YWHAG	Disease-causing germline mutation(s) in	Assessed	HGNC:12852	ENSG00000170027	605356	7q11.23	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma	28777935[PMID]

Prevalence and incidence

1 record

Type	Class	Value	Area	Qualification	Validation	Source
Point prevalence	Unknown	—	Worldwide	Class only	Validated	ORPHANET

Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.

HPO phenotypes

48 annotations · validated 2019-01-30

HPO	Term (as annotated by Orphanet)	Diagnostic
Very frequent (99-80%)
HP:0001298	Encephalopathy
Frequent (79-30%)
HP:0011443	Abnormality of coordination
HP:0000750	Delayed speech and language development
HP:0002376	Developmental regression
HP:0010844	EEG with multifocal slow activity
HP:0001508	Failure to thrive
HP:0001290	Generalized hypotonia
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001249	Intellectual disability
HP:0001250	Seizure
Occasional (29-5%)
HP:0001273	Abnormal corpus callosum morphology
HP:0012447	Abnormal myelination
HP:0001251	Ataxia
HP:0007018	Attention deficit hyperactivity disorder
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0012444	Brain atrophy
HP:0002059	Cerebral atrophy
HP:0001558	Decreased fetal movement
HP:0000494	Downslanted palpebral fissures
HP:0100660	Dyskinesia
HP:0011968	Feeding difficulties
HP:0001288	Gait disturbance
HP:0002020	Gastroesophageal reflux
HP:0000348	High forehead
HP:0000668	Hypodontia
HP:0002521	Hypsarrhythmia
HP:0100710	Impulsivity
HP:0004305	Involuntary movements
HP:0001268	Mental deterioration
HP:0000252	Microcephaly
HP:0001336	Myoclonus
HP:0000639	Nystagmus
HP:0002421	Poor head control
HP:0000508	Ptosis
HP:0001315	Reduced tendon reflexes
HP:0002063	Rigidity
HP:0004322	Short stature
HP:0001257	Spasticity
HP:0001337	Tremor
HP:0002317	Unsteady gait
Very rare (<4-1%)
HP:0012547	Abnormal involuntary eye movements
HP:0000504	Abnormality of vision
HP:0002509	Limb hypertonia
HP:0000648	Optic atrophy
HP:0000546	Retinal degeneration
HP:0002133	Status epilepticus

Run the differential on the 1 obligate / very frequent terms

Annotation source: 28777935[PMID]_27605359[PMID]_27435091[PMID]_27164707[PMID]_25223753[PMID]_23991336[PMID]_27545674[PMID]_27545681[PMID]_26235277[PMID]_26173968[PMID]_27866705[PMID]_23932106[PMID]_25817015[PMID]_24995870[PMID]_25411445[PMID]_23647072[PMID]_25751627[PMID]_25817015[PMID]_25262651[PMID]_23932106[PMID]_28364549[PMID]_25164438[PMID]_24747641[PMID]_24399846[PMID]_22365152[PMID]

Sources for this card

Orphanet page: orpha.net/en/disease/detail/442835
This record as JSON: /data/d/442835.json