MCID: EPL025
MIFTS: 27

Epileptic Encephalopathy, Early Infantile, 2

Categories: Genetic diseases, Neuronal diseases, Rare diseases, Mental diseases, Liver diseases, Metabolic diseases, Muscle diseases, Eye diseases, Fetal diseases

Aliases & Classifications for Epileptic Encephalopathy, Early Infantile, 2

MalaCards integrated aliases for Epileptic Encephalopathy, Early Infantile, 2:

Name: Epileptic Encephalopathy, Early Infantile, 2 57 75 13 73
Eiee2 57 75
Issx2 57 75
Infantile Spasm Syndrome, X-Linked 2; Issx2 57
Rett Syndrome Variant with Infantile Spasms 75
Rett Syndrome Early-Onset Seizure Variant 75
Atypical Rett Syndrome Hanefeld Variant 75
Infantile Spasm Syndrome, X-Linked 2 57
Atypical Rett Syndrome Cdkl5-Related 75
Infantile Spasm Syndrome X-Linked 2 75

Characteristics:

OMIM:

57
Miscellaneous:
onset in infancy
males are more severely affected
seizures are usually refractory
females are most often affected, but rare male cases have been reported
dysmorphic facial features are subtle
some phenotypic overlap with rett syndrome

Inheritance:
x-linked dominant


HPO:

32
epileptic encephalopathy, early infantile, 2:
Onset and clinical course infantile onset
Inheritance x-linked dominant inheritance


Classifications:



Summaries for Epileptic Encephalopathy, Early Infantile, 2

OMIM : 57 Early infantile epileptic encephalopathy-2 is an X-linked dominant severe neurologic disorder characterized by onset of seizures in the first months of life and severe global developmental delay resulting in mental retardation and poor motor control. Other features include lack of speech development, subtle dysmorphic facial features, sleep disturbances, gastrointestinal problems, and stereotypic hand movements. There is some phenotypic overlap with Rett syndrome (312750), but EIEE2 is considered to be a distinct entity (summary by Fehr et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350). (300672)

MalaCards based summary : Epileptic Encephalopathy, Early Infantile, 2, also known as eiee2, is related to rett syndrome, and has symptoms including constipation, myoclonus and difficulty sleeping. An important gene associated with Epileptic Encephalopathy, Early Infantile, 2 is CDKL5 (Cyclin Dependent Kinase Like 5). Affiliated tissues include eye, and related phenotypes are thick lower lip vermilion and progressive microcephaly

UniProtKB/Swiss-Prot : 75 Epileptic encephalopathy, early infantile, 2: A severe form of epilepsy characterized by seizures or spasms beginning in infancy. Patients with epileptic encephalopathy early infantile type 2 manifest features resembling Rett syndrome such as microcephaly, lack of speech development, stereotypic hand movements. However, EIEE2 and Rett syndrome are considered two distinct entities.

Related Diseases for Epileptic Encephalopathy, Early Infantile, 2

Diseases in the Infantile Epileptic Encephalopathy family:

Epileptic Encephalopathy, Early Infantile, 9 Epileptic Encephalopathy, Early Infantile, 8
Epileptic Encephalopathy, Early Infantile, 2 Epileptic Encephalopathy, Early Infantile, 36
Epileptic Encephalopathy, Early Infantile, 1 Epileptic Encephalopathy, Early Infantile, 6
Epileptic Encephalopathy, Early Infantile, 3 Epileptic Encephalopathy, Early Infantile, 4
Epileptic Encephalopathy, Early Infantile, 39 Epileptic Encephalopathy, Early Infantile, 5
Epileptic Encephalopathy, Early Infantile, 7 Epileptic Encephalopathy, Early Infantile, 11
Epileptic Encephalopathy, Early Infantile, 12 Epileptic Encephalopathy, Early Infantile, 13
Epileptic Encephalopathy, Early Infantile, 14 Epileptic Encephalopathy, Early Infantile, 15
Epileptic Encephalopathy, Early Infantile, 16 Epileptic Encephalopathy, Early Infantile, 17
Epileptic Encephalopathy, Early Infantile, 18 Epileptic Encephalopathy, Early Infantile, 19
Epileptic Encephalopathy, Early Infantile, 21 Epileptic Encephalopathy, Early Infantile, 23
Epileptic Encephalopathy, Early Infantile, 24 Epileptic Encephalopathy, Early Infantile, 25
Epileptic Encephalopathy, Early Infantile, 26 Epileptic Encephalopathy, Early Infantile, 27
Epileptic Encephalopathy, Early Infantile, 28 Epileptic Encephalopathy, Early Infantile, 29
Epileptic Encephalopathy, Early Infantile, 30 Epileptic Encephalopathy, Early Infantile, 31
Epileptic Encephalopathy, Early Infantile, 32 Epileptic Encephalopathy, Early Infantile, 33
Epileptic Encephalopathy, Early Infantile, 50 Epileptic Encephalopathy, Early Infantile, 34
Epileptic Encephalopathy, Early Infantile, 35 Epileptic Encephalopathy, Early Infantile, 37
Epileptic Encephalopathy, Early Infantile, 38 Epileptic Encephalopathy, Early Infantile, 40
Epileptic Encephalopathy, Early Infantile, 41 Epileptic Encephalopathy, Early Infantile, 42
Epileptic Encephalopathy, Early Infantile, 43 Epileptic Encephalopathy, Early Infantile, 44
Epileptic Encephalopathy, Early Infantile, 45 Epileptic Encephalopathy, Early Infantile, 46
Epileptic Encephalopathy, Early Infantile, 47 Epileptic Encephalopathy, Early Infantile, 48
Epileptic Encephalopathy, Early Infantile, 49 Epileptic Encephalopathy, Early Infantile, 51
Epileptic Encephalopathy, Early Infantile, 52 Epileptic Encephalopathy, Early Infantile, 53
Epileptic Encephalopathy, Early Infantile, 54 Epileptic Encephalopathy, Early Infantile, 55
Epileptic Encephalopathy, Early Infantile, 56 Epileptic Encephalopathy, Early Infantile, 57
Epileptic Encephalopathy, Early Infantile, 58 Epileptic Encephalopathy, Early Infantile, 59
Epileptic Encephalopathy, Early Infantile, 60 Epileptic Encephalopathy, Early Infantile, 61
Epileptic Encephalopathy, Early Infantile, 62 Epileptic Encephalopathy, Early Infantile, 63
Epileptic Encephalopathy, Early Infantile, 64 Epileptic Encephalopathy, Early Infantile, 65
Infantile Epileptic Encephalopathy 56 Infantile Epileptic Encephalopathy 55
Infantile Epileptic Encephalopathy 57 Infantile Epileptic Encephalopathy 58
Infantile Epileptic Encephalopathy 59

Diseases related to Epileptic Encephalopathy, Early Infantile, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 rett syndrome 10.0

Symptoms & Phenotypes for Epileptic Encephalopathy, Early Infantile, 2

Symptoms via clinical synopsis from OMIM:

57
Abdomen Gastrointestinal:
constipation
gastroesophageal reflux

Head And Neck Nose:
anteverted nares

Neurologic Central Nervous System:
myoclonus
generalized seizures
infantile spasms
hypsarrhythmia
poor eye contact
more
Muscle Soft Tissue:
hypotonia

Neurologic Behavioral Psychiatric Manifestations:
autistic features
breath-holding episodes
stereotyped behaviors
hand-wringing

Head And Neck Mouth:
full lips

Head And Neck Head:
microcephaly, progressive

Skeletal Spine:
scoliosis

Head And Neck Face:
prominent forehead
broad forehead

Respiratory:
hyperventilation
breath-holding episodes

Head And Neck Eyes:
well-defined eyebrows
deep-set eyes
large-appearing eyes

Skeletal Hands:
small hands
tapering fingers

Skeletal Feet:
small feet


Clinical features from OMIM:

300672

Human phenotypes related to Epileptic Encephalopathy, Early Infantile, 2:

32 (show all 31)
# Description HPO Frequency HPO Source Accession
1 thick lower lip vermilion 32 HP:0000179
2 progressive microcephaly 32 HP:0000253
3 broad forehead 32 HP:0000337
4 anteverted nares 32 HP:0000463
5 deeply set eye 32 HP:0000490
6 stereotypy 32 HP:0000733
7 poor eye contact 32 HP:0000817
8 tapered finger 32 HP:0001182
9 seizures 32 HP:0001250
10 muscular hypotonia 32 HP:0001252
11 global developmental delay 32 HP:0001263
12 generalized hypotonia 32 HP:0001290
13 myoclonus 32 HP:0001336
14 short foot 32 HP:0001773
15 constipation 32 HP:0002019
16 gastroesophageal reflux 32 HP:0002020
17 generalized myoclonic seizures 32 HP:0002123
18 intellectual disability, profound 32 HP:0002187
19 developmental regression 32 HP:0002376
20 hypsarrhythmia 32 HP:0002521
21 inability to walk 32 HP:0002540
22 scoliosis 32 HP:0002650
23 hyperventilation 32 HP:0002883
24 short palm 32 HP:0004279
25 eeg with generalized slow activity 32 very rare (1%) HP:0010845
26 prominent forehead 32 HP:0011220
27 infantile spasms 32 HP:0012469
28 multifocal seizures 32 HP:0031165
29 cortical visual impairment 32 HP:0100704
30 small hand 32 HP:0200055
31 epileptic encephalopathy 32 HP:0200134

UMLS symptoms related to Epileptic Encephalopathy, Early Infantile, 2:


constipation, myoclonus, difficulty sleeping, myoclonic seizures

Drugs & Therapeutics for Epileptic Encephalopathy, Early Infantile, 2

Search Clinical Trials , NIH Clinical Center for Epileptic Encephalopathy, Early Infantile, 2

Genetic Tests for Epileptic Encephalopathy, Early Infantile, 2

Anatomical Context for Epileptic Encephalopathy, Early Infantile, 2

MalaCards organs/tissues related to Epileptic Encephalopathy, Early Infantile, 2:

41
Eye

Publications for Epileptic Encephalopathy, Early Infantile, 2

Articles related to Epileptic Encephalopathy, Early Infantile, 2:

# Title Authors Year
1
CDKL5/STK9 is mutated in Rett syndrome variant with infantile spasms. ( 15689447 )
2005

Variations for Epileptic Encephalopathy, Early Infantile, 2

UniProtKB/Swiss-Prot genetic disease variations for Epileptic Encephalopathy, Early Infantile, 2:

75 (show all 18)
# Symbol AA change Variation ID SNP ID
1 CDKL5 p.Cys152Phe VAR_023560 rs122460157
2 CDKL5 p.Arg175Ser VAR_023561 rs61749700
3 CDKL5 p.Pro180Leu VAR_037635 rs61749704
4 CDKL5 p.Ala40Val VAR_058022 rs122460159
5 CDKL5 p.Ile72Asn VAR_058023 rs62641235
6 CDKL5 p.Ile72Thr VAR_058024 rs62641235
7 CDKL5 p.His127Arg VAR_058025 rs267608468
8 CDKL5 p.Arg178Pro VAR_058026 rs267606715
9 CDKL5 p.Leu220Pro VAR_058027 rs267608511
10 CDKL5 p.Thr288Ile VAR_058028 rs267606713
11 CDKL5 p.Cys291Tyr VAR_058029 rs267606714
12 CDKL5 p.Asn399Thr VAR_058030 rs267608611
13 CDKL5 p.Val718Met VAR_058032 rs267608653
14 CDKL5 p.Arg178Gln VAR_071103 rs267606715
15 CDKL5 p.Ser196Leu VAR_078219 rs267608501
16 CDKL5 p.Leu182Pro VAR_078626
17 CDKL5 p.Gly207Glu VAR_078627
18 CDKL5 p.Arg178Trp VAR_078712 rs267608493

ClinVar genetic disease variations for Epileptic Encephalopathy, Early Infantile, 2:

6
(show top 50) (show all 343)
# Gene Variation Type Significance SNP ID Assembly Location
1 CDKL5 CDKL5, 1-BP DEL, 183T deletion Pathogenic
2 CDKL5 CDKL5, IVSAS13, G-A, -1 single nucleotide variant Pathogenic
3 CDKL5 NM_003159.2(CDKL5): c.455G> T (p.Cys152Phe) single nucleotide variant Pathogenic rs122460157 GRCh37 Chromosome X, 18600062: 18600062
4 CDKL5 NM_003159.2(CDKL5): c.455G> T (p.Cys152Phe) single nucleotide variant Pathogenic rs122460157 GRCh38 Chromosome X, 18581942: 18581942
5 CDKL5 NM_003159.2(CDKL5): c.525A> T (p.Arg175Ser) single nucleotide variant Pathogenic rs61749700 GRCh37 Chromosome X, 18602444: 18602444
6 CDKL5 NM_003159.2(CDKL5): c.525A> T (p.Arg175Ser) single nucleotide variant Pathogenic rs61749700 GRCh38 Chromosome X, 18584324: 18584324
7 CDKL5 CDKL5, 4-BP DEL, 166GAAA deletion Pathogenic
8 CDKL5 CDKL5, 2-BP DEL, 2636CT deletion Pathogenic
9 CDKL5 NM_003159.2(CDKL5): c.2500C> T (p.Gln834Ter) single nucleotide variant Pathogenic rs122460158 GRCh37 Chromosome X, 18646494: 18646494
10 CDKL5 NM_003159.2(CDKL5): c.2500C> T (p.Gln834Ter) single nucleotide variant Pathogenic rs122460158 GRCh38 Chromosome X, 18628374: 18628374
11 CDKL5 CDKL5, IVS6AS, G-T, -1 single nucleotide variant Pathogenic
12 CDKL5 NM_003159.2(CDKL5): c.119C> T (p.Ala40Val) single nucleotide variant Pathogenic rs122460159 GRCh37 Chromosome X, 18582616: 18582616
13 CDKL5 NM_003159.2(CDKL5): c.119C> T (p.Ala40Val) single nucleotide variant Pathogenic rs122460159 GRCh38 Chromosome X, 18564496: 18564496
14 CDKL5 NM_003159.2(CDKL5): c.215T> C (p.Ile72Thr) single nucleotide variant Pathogenic rs62641235 GRCh37 Chromosome X, 18593543: 18593543
15 CDKL5 NM_003159.2(CDKL5): c.215T> C (p.Ile72Thr) single nucleotide variant Pathogenic rs62641235 GRCh38 Chromosome X, 18575423: 18575423
16 CDKL5 NM_003159.2(CDKL5): c.863C> T (p.Thr288Ile) single nucleotide variant Pathogenic rs267606713 GRCh37 Chromosome X, 18616619: 18616619
17 CDKL5 NM_003159.2(CDKL5): c.863C> T (p.Thr288Ile) single nucleotide variant Pathogenic rs267606713 GRCh38 Chromosome X, 18598499: 18598499
18 CDKL5 CDKL5, 2-BP INS, 903GA insertion Pathogenic
19 CDKL5 NM_003159.2(CDKL5): c.533G> C (p.Arg178Pro) single nucleotide variant Pathogenic rs267606715 GRCh37 Chromosome X, 18602452: 18602452
20 CDKL5 NM_003159.2(CDKL5): c.533G> C (p.Arg178Pro) single nucleotide variant Pathogenic rs267606715 GRCh38 Chromosome X, 18584332: 18584332
21 CDKL5 NM_003159.2(CDKL5): c.533G> A (p.Arg178Gln) single nucleotide variant Pathogenic/Likely pathogenic rs267606715 GRCh37 Chromosome X, 18602452: 18602452
22 CDKL5 NM_003159.2(CDKL5): c.533G> A (p.Arg178Gln) single nucleotide variant Pathogenic/Likely pathogenic rs267606715 GRCh38 Chromosome X, 18584332: 18584332
23 CDKL5 NM_003159.2(CDKL5): c.1039C> T (p.Gln347Ter) single nucleotide variant Pathogenic rs267608561 GRCh37 Chromosome X, 18622083: 18622083
24 CDKL5 NM_003159.2(CDKL5): c.1039C> T (p.Gln347Ter) single nucleotide variant Pathogenic rs267608561 GRCh38 Chromosome X, 18603963: 18603963
25 CDKL5 NM_003159.2(CDKL5): c.1079delT (p.Leu360Profs) deletion Pathogenic rs267608565 GRCh37 Chromosome X, 18622123: 18622123
26 CDKL5 NM_003159.2(CDKL5): c.1079delT (p.Leu360Profs) deletion Pathogenic rs267608565 GRCh38 Chromosome X, 18604003: 18604003
27 CDKL5 NM_003159.2(CDKL5): c.1082dupC (p.Ala362Cysfs) duplication Pathogenic rs267608566 GRCh37 Chromosome X, 18622126: 18622126
28 CDKL5 NM_003159.2(CDKL5): c.1082dupC (p.Ala362Cysfs) duplication Pathogenic rs267608566 GRCh38 Chromosome X, 18604006: 18604006
29 CDKL5 NM_003159.2(CDKL5): c.1238C> G (p.Ser413Ter) single nucleotide variant Pathogenic rs267608618 GRCh37 Chromosome X, 18622282: 18622282
30 CDKL5 NM_003159.2(CDKL5): c.1238C> G (p.Ser413Ter) single nucleotide variant Pathogenic rs267608618 GRCh38 Chromosome X, 18604162: 18604162
31 CDKL5 NM_003159.2(CDKL5): c.125A> G (p.Lys42Arg) single nucleotide variant Pathogenic rs267608429 GRCh37 Chromosome X, 18582622: 18582622
32 CDKL5 NM_003159.2(CDKL5): c.125A> G (p.Lys42Arg) single nucleotide variant Pathogenic rs267608429 GRCh38 Chromosome X, 18564502: 18564502
33 CDKL5 NM_003159.2(CDKL5): c.163_166delGAAA (p.Glu55Argfs) deletion Likely pathogenic rs267608433 GRCh37 Chromosome X, 18593491: 18593494
34 CDKL5 NM_003159.2(CDKL5): c.163_166delGAAA (p.Glu55Argfs) deletion Likely pathogenic rs267608433 GRCh38 Chromosome X, 18575371: 18575374
35 CDKL5 NM_003159.2(CDKL5): c.1648C> T (p.Arg550Ter) single nucleotide variant Pathogenic rs267608643 GRCh37 Chromosome X, 18622692: 18622692
36 CDKL5 NM_003159.2(CDKL5): c.1648C> T (p.Arg550Ter) single nucleotide variant Pathogenic rs267608643 GRCh38 Chromosome X, 18604572: 18604572
37 CDKL5 NM_003159.2(CDKL5): c.1675C> T (p.Arg559Ter) single nucleotide variant Pathogenic rs267608395 GRCh37 Chromosome X, 18622719: 18622719
38 CDKL5 NM_003159.2(CDKL5): c.1675C> T (p.Arg559Ter) single nucleotide variant Pathogenic rs267608395 GRCh38 Chromosome X, 18604599: 18604599
39 CDKL5 NM_003159.2(CDKL5): c.175C> T (p.Arg59Ter) single nucleotide variant Pathogenic rs62653623 GRCh37 Chromosome X, 18593503: 18593503
40 CDKL5 NM_003159.2(CDKL5): c.175C> T (p.Arg59Ter) single nucleotide variant Pathogenic rs62653623 GRCh38 Chromosome X, 18575383: 18575383
41 CDKL5 NM_003159.2(CDKL5): c.183delT (p.Met63Cysfs) deletion Pathogenic rs62643608 GRCh37 Chromosome X, 18593511: 18593511
42 CDKL5 NM_003159.2(CDKL5): c.183delT (p.Met63Cysfs) deletion Pathogenic rs62643608 GRCh38 Chromosome X, 18575391: 18575391
43 CDKL5 NM_003159.2(CDKL5): c.191T> C (p.Leu64Pro) single nucleotide variant Likely pathogenic rs267608435 GRCh37 Chromosome X, 18593519: 18593519
44 CDKL5 NM_003159.2(CDKL5): c.191T> C (p.Leu64Pro) single nucleotide variant Likely pathogenic rs267608435 GRCh38 Chromosome X, 18575399: 18575399
45 CDKL5 NM_003159.2(CDKL5): c.1954C> T (p.Gln652Ter) single nucleotide variant Pathogenic rs267608647 GRCh37 Chromosome X, 18626940: 18626940
46 CDKL5 NM_003159.2(CDKL5): c.1954C> T (p.Gln652Ter) single nucleotide variant Pathogenic rs267608647 GRCh38 Chromosome X, 18608820: 18608820
47 CDKL5 NM_003159.2(CDKL5): c.199C> T (p.Leu67Phe) single nucleotide variant Pathogenic rs267608437 GRCh37 Chromosome X, 18593527: 18593527
48 CDKL5 NM_003159.2(CDKL5): c.199C> T (p.Leu67Phe) single nucleotide variant Pathogenic rs267608437 GRCh38 Chromosome X, 18575407: 18575407
49 CDKL5 NM_003159.2(CDKL5): c.2016delC (p.Ser673Leufs) deletion Pathogenic rs267608648 GRCh37 Chromosome X, 18627002: 18627002
50 CDKL5 NM_003159.2(CDKL5): c.2016delC (p.Ser673Leufs) deletion Pathogenic rs267608648 GRCh38 Chromosome X, 18608882: 18608882

Expression for Epileptic Encephalopathy, Early Infantile, 2

Search GEO for disease gene expression data for Epileptic Encephalopathy, Early Infantile, 2.

Pathways for Epileptic Encephalopathy, Early Infantile, 2

GO Terms for Epileptic Encephalopathy, Early Infantile, 2

Sources for Epileptic Encephalopathy, Early Infantile, 2

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