MCID: EPL025
MIFTS: 27

Epileptic Encephalopathy, Early Infantile, 2

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

Aliases & Classifications for Epileptic Encephalopathy, Early Infantile, 2

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

Name: Epileptic Encephalopathy, Early Infantile, 2 53 71 13 69
Eiee2 53 71
Issx2 53 71
Infantile Spasm Syndrome, X-Linked 2; Issx2 53
Rett Syndrome Variant with Infantile Spasms 71
Rett Syndrome Early-Onset Seizure Variant 71
Atypical Rett Syndrome Hanefeld Variant 71
Infantile Spasm Syndrome, X-Linked 2 53
Atypical Rett Syndrome Cdkl5-Related 71
Infantile Spasm Syndrome X-Linked 2 71

Characteristics:

OMIM:

53
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:

31
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 : 53 EIEE2 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 developmental regression. An important gene associated with Epileptic Encephalopathy, Early Infantile, 2 is CDKL5 (Cyclin Dependent Kinase Like 5). Affiliated tissues include eye.

UniProtKB/Swiss-Prot : 71 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

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:

53
Abdomen Gastroin testinal:
constipation
gastroesophageal reflux

Skeletal Spine:
scoliosis

Head And Neck Face:
prominent forehead
broad forehead

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

Neurologic Central Nervous System:
myoclonus
generalized seizures
infantile spasms
hypsarrhythmia
poor eye contact
more
Head And Neck Nose:
anteverted nares

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:

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

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


myoclonic seizures, difficulty sleeping, myoclonus, constipation

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:

38
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:

71 (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 126)
# 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.525A> T (p.Arg175Ser) single nucleotide variant Pathogenic rs61749700 GRCh37 Chromosome X, 18602444: 18602444
5 CDKL5 CDKL5, 4-BP DEL, 166GAAA deletion Pathogenic
6 CDKL5 CDKL5, 2-BP DEL, 2636CT deletion Pathogenic
7 CDKL5 NM_003159.2(CDKL5): c.2500C> T (p.Gln834Ter) single nucleotide variant Pathogenic rs122460158 GRCh37 Chromosome X, 18646494: 18646494
8 CDKL5 CDKL5, IVS6AS, G-T, -1 single nucleotide variant Pathogenic
9 CDKL5 NM_003159.2(CDKL5): c.119C> T (p.Ala40Val) single nucleotide variant Pathogenic rs122460159 GRCh37 Chromosome X, 18582616: 18582616
10 CDKL5 NM_003159.2(CDKL5): c.863C> T (p.Thr288Ile) single nucleotide variant Pathogenic rs267606713 GRCh37 Chromosome X, 18616619: 18616619
11 CDKL5 CDKL5, 2-BP INS, 903GA insertion Pathogenic
12 CDKL5 NM_003159.2(CDKL5): c.533G> C (p.Arg178Pro) single nucleotide variant Pathogenic rs267606715 GRCh37 Chromosome X, 18602452: 18602452
13 CDKL5 NM_003159.2(CDKL5): c.533G> A (p.Arg178Gln) single nucleotide variant Pathogenic/Likely pathogenic rs267606715 GRCh37 Chromosome X, 18602452: 18602452
14 CDKL5 NM_003159.2(CDKL5): c.1039C> T (p.Gln347Ter) single nucleotide variant Pathogenic rs267608561 GRCh37 Chromosome X, 18622083: 18622083
15 CDKL5 NM_003159.2(CDKL5): c.1079delT (p.Leu360Profs) deletion Pathogenic rs267608565 GRCh37 Chromosome X, 18622123: 18622123
16 CDKL5 NM_003159.2(CDKL5): c.1082dupC (p.Ala362Cysfs) duplication Pathogenic rs267608566 GRCh37 Chromosome X, 18622126: 18622126
17 CDKL5 NM_003159.2(CDKL5): c.1238C> G (p.Ser413Ter) single nucleotide variant Pathogenic rs267608618 GRCh37 Chromosome X, 18622282: 18622282
18 CDKL5 NM_003159.2(CDKL5): c.125A> G (p.Lys42Arg) single nucleotide variant Pathogenic rs267608429 GRCh37 Chromosome X, 18582622: 18582622
19 CDKL5 NM_003159.2(CDKL5): c.163_166delGAAA (p.Glu55Argfs) deletion Pathogenic rs267608433 GRCh37 Chromosome X, 18593491: 18593494
20 CDKL5 NM_003159.2(CDKL5): c.1648C> T (p.Arg550Ter) single nucleotide variant Pathogenic rs267608643 GRCh37 Chromosome X, 18622692: 18622692
21 CDKL5 NM_003159.2(CDKL5): c.1675C> T (p.Arg559Ter) single nucleotide variant Pathogenic rs267608395 GRCh37 Chromosome X, 18622719: 18622719
22 CDKL5 NM_003159.2(CDKL5): c.175C> T (p.Arg59Ter) single nucleotide variant Pathogenic rs62653623 GRCh37 Chromosome X, 18593503: 18593503
23 CDKL5 NM_003159.2(CDKL5): c.183delT (p.Met63Cysfs) deletion Pathogenic rs62643608 GRCh37 Chromosome X, 18593511: 18593511
24 CDKL5 NM_003159.2(CDKL5): c.191T> C (p.Leu64Pro) single nucleotide variant Likely pathogenic rs267608435 GRCh37 Chromosome X, 18593519: 18593519
25 CDKL5 NM_003159.2(CDKL5): c.1954C> T (p.Gln652Ter) single nucleotide variant Pathogenic rs267608647 GRCh37 Chromosome X, 18626940: 18626940
26 CDKL5 NM_003159.2(CDKL5): c.199C> T (p.Leu67Phe) single nucleotide variant Pathogenic/Likely pathogenic rs267608437 GRCh37 Chromosome X, 18593527: 18593527
27 CDKL5 NM_003159.2(CDKL5): c.2016delC (p.Ser673Leufs) deletion Pathogenic rs267608648 GRCh37 Chromosome X, 18627002: 18627002
28 CDKL5 NM_003159.2(CDKL5): c.2016dupC (p.Ser673Leufs) duplication Pathogenic rs267608649 GRCh37 Chromosome X, 18627002: 18627002
29 CDKL5 NM_003159.2(CDKL5): c.2066delC (p.Pro689Hisfs) deletion Pathogenic rs267608651 GRCh37 Chromosome X, 18627604: 18627604
30 CDKL5 NM_003159.2(CDKL5): c.2152G> A (p.Val718Met) single nucleotide variant Pathogenic/Likely pathogenic rs267608653 GRCh37 Chromosome X, 18627690: 18627690
31 CDKL5 NM_003159.2(CDKL5): c.229_232delGAAG (p.Glu77Hisfs) deletion Pathogenic rs267608441 GRCh37 Chromosome X, 18593557: 18593560
32 CDKL5 NM_003159.2(CDKL5): c.2325_2326delGA (p.Lys776Alafs) deletion Pathogenic rs267608654 GRCh37 Chromosome X, 18638035: 18638036
33 CDKL5 NM_003159.2(CDKL5): c.2363_2367delAGAAA (p.Lys788Ilefs) deletion Pathogenic rs267608655 GRCh37 Chromosome X, 18638073: 18638077
34 CDKL5 NM_003159.2(CDKL5): c.2413C> T (p.Gln805Ter) single nucleotide variant Pathogenic rs267608659 GRCh37 Chromosome X, 18643284: 18643284
35 CDKL5 NM_003159.2(CDKL5): c.2504delC (p.Pro835Hisfs) deletion Pathogenic rs267608660 GRCh37 Chromosome X, 18646498: 18646498
36 CDKL5 NM_003159.2(CDKL5): c.2529delA (p.Leu843Phefs) deletion Pathogenic rs267608661 GRCh37 Chromosome X, 18646523: 18646523
37 CDKL5 NM_003159.2(CDKL5): c.2572delC (p.Arg858Alafs) deletion Pathogenic rs267608662 GRCh37 Chromosome X, 18646566: 18646566
38 CDKL5 NM_003159.2(CDKL5): c.2593C> T (p.Gln865Ter) single nucleotide variant Pathogenic rs267608663 GRCh37 Chromosome X, 18646587: 18646587
39 CDKL5 NM_003159.2(CDKL5): c.2635_2636delCT (p.Leu879Glufs) deletion Pathogenic rs61753251 GRCh37 Chromosome X, 18646629: 18646630
40 CDKL5 NM_003159.2(CDKL5): c.39delT (p.Phe13Leufs) deletion Pathogenic rs267608415 GRCh37 Chromosome X, 18525255: 18525255
41 CDKL5 NM_003159.2(CDKL5): c.400C> T (p.Arg134Ter) single nucleotide variant Pathogenic rs267608472 GRCh37 Chromosome X, 18598085: 18598085
42 CDKL5 NM_003159.2(CDKL5): c.425T> A (p.Leu142Ter) single nucleotide variant Pathogenic rs267608477 GRCh37 Chromosome X, 18600032: 18600032
43 CDKL5 NM_003159.2(CDKL5): c.513C> A (p.Tyr171Ter) single nucleotide variant Pathogenic rs267608490 GRCh37 Chromosome X, 18602432: 18602432
44 CDKL5 NM_003159.2(CDKL5): c.532C> T (p.Arg178Trp) single nucleotide variant Pathogenic/Likely pathogenic rs267608493 GRCh37 Chromosome X, 18602451: 18602451
45 CDKL5 NM_003159.2(CDKL5): c.539C> T (p.Pro180Leu) single nucleotide variant Pathogenic rs61749704 GRCh37 Chromosome X, 18602458: 18602458
46 CDKL5 NM_003159.2(CDKL5): c.549dupA (p.Leu184Thrfs) duplication Pathogenic rs267608497 GRCh37 Chromosome X, 18602468: 18602468
47 CDKL5 NM_003159.2(CDKL5): c.578A> G (p.Asp193Gly) single nucleotide variant Pathogenic rs267608500 GRCh37 Chromosome X, 18606097: 18606097
48 CDKL5 NM_003159.2(CDKL5): c.587C> T (p.Ser196Leu) single nucleotide variant Pathogenic/Likely pathogenic rs267608501 GRCh38 Chromosome X, 18587986: 18587986
49 CDKL5 NM_003159.2(CDKL5): c.58G> C (p.Gly20Arg) single nucleotide variant Likely pathogenic rs267608418 GRCh37 Chromosome X, 18525274: 18525274
50 CDKL5 NM_003159.2(CDKL5): c.659T> C (p.Leu220Pro) single nucleotide variant Pathogenic rs267608511 GRCh37 Chromosome X, 18606178: 18606178

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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