EIEE2
MCID: EPL025
MIFTS: 49

Epileptic Encephalopathy, Early Infantile, 2 (EIEE2)

Categories: Bone diseases, Ear diseases, Eye diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Liver diseases, Mental diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Oral diseases, Rare diseases

Aliases & Classifications for Epileptic Encephalopathy, Early Infantile, 2

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

Name: Epileptic Encephalopathy, Early Infantile, 2 56 73 13 71
Early Infantile Epileptic Encephalopathy 2 12 25 29 6 15
Cdkl5 Deficiency Disorder 52 25 58
Cdkl5-Related Epileptic Encephalopathy 25 58
Cdkl5 Deficiency 52 25
Cdkl5 Disorder 52 25
Eiee2 56 73
Issx2 56 73
Encephalopathy, Epileptic, Early Infantile, Type 2 39
X-Linked Dominant Infantile Spasm Syndrome-2 52
Infantile Spasm Syndrome, X-Linked 2; Issx2 56
Rett Syndrome Variant with Infantile Spasms 73
Early Infantile Epileptic Encephalopathy-2 52
Rett Syndrome Early-Onset Seizure Variant 73
Atypical Rett Syndrome Hanefeld Variant 73
Infantile Spasm Syndrome, X-Linked 2 56
Atypical Rett Syndrome Cdkl5-Related 73
X-Linked Infantile Spasm Syndrome 2 12
Infantile Spasm Syndrome X-Linked 2 73
Cdkl5-Related Disorder 52
Cdkl5-Related Epilepsy 25
Cdkl5 Encephalopathy 25
Cdkl5 52

Characteristics:

OMIM:

56
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:

Orphanet: 58  
Rare neurological diseases


Summaries for Epileptic Encephalopathy, Early Infantile, 2

Genetics Home Reference : 25 CDKL5 deficiency disorder is characterized by seizures that begin in infancy, followed by significant delays in many aspects of development. Seizures in CDKL5 deficiency disorder usually begin within the first 3 months of life, and they can appear as early as the first week after birth. The types of seizures change with age, and they usually follow a predictable pattern. Seizures occur daily in most affected individuals, and they are resistant to treatment. Development is impaired in children with CDKL5 deficiency disorder. Most have severe intellectual disability and little or no speech. The development of gross motor skills, such as sitting, standing, and walking, is delayed. About one-third of affected individuals are able to walk independently. Fine motor skills, such as picking up small objects with the fingers, are also impaired; about half of affected individuals have purposeful use of their hands. Other common features of CDKL5 deficiency disorder include repetitive hand movements (stereotypies), such as clapping, hand licking, and hand sucking; tooth grinding (bruxism); disrupted sleep; feeding difficulties; and gastrointestinal problems including constipation and backflow of acidic stomach contents into the esophagus (gastroesophageal reflux). Some affected individuals have episodes of irregular breathing. Distinctive facial features in some people with CDKL5 deficiency disorder include a high and broad forehead, large and deep-set eyes, a well-defined space between the nose and upper lip (philtrum), full lips, widely spaced teeth, and a high roof of the mouth (palate). Other physical differences can also occur, such as an unusually small head size (microcephaly), side-to-side curvature of the spine (scoliosis), and tapered fingers. About 90 percent of people diagnosed with CDKL5 deficiency disorder are female. Affected males tend to have more severe developmental disabilities, including profound intellectual disability and almost no development of gross and fine motor skills. CDKL5 deficiency disorder was previously classified as an atypical form of Rett syndrome. These conditions have overlapping features, including seizures, intellectual disability, and other problems with development. However, the signs and symptoms associated with CDKL5 deficiency disorder and its genetic cause are distinct from those of Rett syndrome, and CDKL5 deficiency disorder is now considered a separate condition.

MalaCards based summary : Epileptic Encephalopathy, Early Infantile, 2, also known as early infantile epileptic encephalopathy 2, is related to epileptic encephalopathy, early infantile, 6 and landau-kleffner 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). The drugs Anticonvulsants and Neurotransmitter Agents have been mentioned in the context of this disorder. Affiliated tissues include eye, bone and liver, and related phenotypes are eeg with generalized slow activity and scoliosis

Disease Ontology : 12 An early infantile epileptic encephalopathy characterized by X-linked dominant inheritance of seizure onset in the first months of life, intellectual disability, and poor motor control that has material basis in mutation in the CDKL5 gene on chromosome Xp22.

NIH Rare Diseases : 52 CDKL5 deficiency disorder is a genetic disorder that causes seizures , developmental delay , and severe intellectual disability . Seizures typically begin within a few months after birth and are difficult to control with medications. Most children have 1 to 5 seizures every day. Other symptoms include problems with sleeping, feeding, and teeth grinding. Gastrointestinal symptoms are also common and may include constipation, reflux, and air swallowing. About 1 in 5 children use a feeding tube . CDKL5 deficiency disorder occurs more often in females than males, and males usually have more severe symptoms. This disorder is caused by a change (pathogenic variant) in the CDKL5 gene that is usually not inherited from either parent (de novo ). It is an X-linked dominant disorder. CDKL5 deficiency disorder was once thought to be a variant of Rett syndrome but is now considered a separate disorder.

OMIM : 56 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)

UniProtKB/Swiss-Prot : 73 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 Early 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, 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 Epileptic Encephalopathy, Early Infantile, 66
Epileptic Encephalopathy, Early Infantile, 67 Epileptic Encephalopathy, Early Infantile, 68
Epileptic Encephalopathy, Early Infantile, 69 Epileptic Encephalopathy, Early Infantile, 70
Epileptic Encephalopathy, Early Infantile, 71 Epileptic Encephalopathy, Early Infantile, 72
Epileptic Encephalopathy, Early Infantile, 73 Epileptic Encephalopathy, Early Infantile, 74
Epileptic Encephalopathy, Early Infantile, 75 Epileptic Encephalopathy, Early Infantile, 76
Epileptic Encephalopathy, Early Infantile, 77 Epileptic Encephalopathy, Early Infantile, 78
Epileptic Encephalopathy, Early Infantile, 79 Epileptic Encephalopathy, Early Infantile, 80
Epileptic Encephalopathy, Early Infantile, 81 Epileptic Encephalopathy, Early Infantile, 82
Epileptic Encephalopathy, Early Infantile, 83 Arx-Related Epileptic Encephalopathy

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

(show top 50) (show all 83)
# Related Disease Score Top Affiliating Genes
1 epileptic encephalopathy, early infantile, 6 31.5 CNTNAP2 CDKL5
2 landau-kleffner syndrome 31.4 CNTNAP2 CDKL5
3 pitt-hopkins syndrome 31.4 CNTNAP2 CDKL5
4 kleefstra syndrome 1 31.2 NSD1 CDKL5
5 early infantile epileptic encephalopathy 11.7
6 autism 11.6
7 early myoclonic encephalopathy 11.5
8 microcephaly 11.5
9 benign neonatal seizures 11.3
10 47, xxy 11.3
11 angelman syndrome 11.2
12 focal epilepsy 11.2
13 bruxism 11.2
14 amyotrophic lateral sclerosis 1 11.2
15 methylmalonic acidemia 11.2
16 mowat-wilson syndrome 11.0
17 epilepsy, myoclonic juvenile 11.0
18 epileptic encephalopathy, early infantile, 9 11.0
19 lubs x-linked mental retardation syndrome 11.0
20 epilepsy, idiopathic generalized 11.0
21 nicolaides-baraitser syndrome 11.0
22 myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency 11.0
23 lennox-gastaut syndrome 11.0
24 electroclinical syndrome 11.0
25 neonatal period electroclinical syndrome 11.0
26 infancy electroclinical syndrome 11.0
27 childhood electroclinical syndrome 11.0
28 specific developmental disorder 11.0
29 pervasive developmental disorder 11.0
30 benign familial infantile epilepsy 11.0
31 generalized epilepsy with febrile seizures plus 11.0
32 christianson syndrome 11.0
33 benign familial neonatal epilepsy 11.0
34 childhood absence epilepsy 11.0
35 congenital nervous system abnormality 11.0
36 benign epilepsy with centrotemporal spikes 11.0
37 gait apraxia 11.0
38 hypotonia 10.5
39 alacrima, achalasia, and mental retardation syndrome 10.4
40 rett syndrome 10.3
41 epilepsy 10.3
42 myoclonus 10.2
43 visual epilepsy 10.2
44 seizure disorder 10.2
45 cerebral visual impairment 10.2
46 epileptic encephalopathy, early infantile, 15 10.1
47 autism spectrum disorder 10.1
48 neuroblastoma 10.1
49 15q duplication syndrome and related disorders 10.1
50 infantile epilepsy syndrome 10.1

Graphical network of the top 20 diseases related to Epileptic Encephalopathy, Early Infantile, 2:



Diseases related to Epileptic Encephalopathy, Early Infantile, 2

Symptoms & Phenotypes for Epileptic Encephalopathy, Early Infantile, 2

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

31 58 (show top 50) (show all 57)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 eeg with generalized slow activity 31 very rare (1%) HP:0010845
2 scoliosis 58 31 Occasional (29-5%) HP:0002650
3 prominent forehead 58 31 Frequent (79-30%) HP:0011220
4 broad forehead 58 31 Frequent (79-30%) HP:0000337
5 deeply set eye 58 31 Frequent (79-30%) HP:0000490
6 infantile spasms 58 31 Frequent (79-30%) HP:0012469
7 poor eye contact 58 31 Frequent (79-30%) HP:0000817
8 seizures 31 HP:0001250
9 gait disturbance 58 Frequent (79-30%)
10 constipation 31 HP:0002019
11 kyphosis 58 Occasional (29-5%)
12 muscular hypotonia 31 HP:0001252
13 developmental regression 31 HP:0002376
14 global developmental delay 31 HP:0001263
15 thick vermilion border 58 Frequent (79-30%)
16 hallux valgus 58 Occasional (29-5%)
17 delayed gross motor development 58 Frequent (79-30%)
18 anteverted nares 31 HP:0000463
19 gastroesophageal reflux 31 HP:0002020
20 myoclonus 31 HP:0001336
21 stereotypy 31 HP:0000733
22 narrow forehead 58 Occasional (29-5%)
23 generalized hypotonia 31 HP:0001290
24 generalized myoclonic seizures 31 HP:0002123
25 thick lower lip vermilion 31 HP:0000179
26 short palm 31 HP:0004279
27 severe global developmental delay 58 Frequent (79-30%)
28 short foot 31 HP:0001773
29 everted lower lip vermilion 58 Frequent (79-30%)
30 growth delay 58 Frequent (79-30%)
31 inability to walk 31 HP:0002540
32 small hand 31 HP:0200055
33 synophrys 58 Occasional (29-5%)
34 high forehead 58 Occasional (29-5%)
35 deep philtrum 58 Frequent (79-30%)
36 generalized tonic seizures 58 Very frequent (99-80%)
37 epileptic encephalopathy 31 HP:0200134
38 functional respiratory abnormality 58 Occasional (29-5%)
39 hypsarrhythmia 31 HP:0002521
40 focal-onset seizure 58 Frequent (79-30%)
41 impaired pain sensation 58 Frequent (79-30%)
42 sleep-wake cycle disturbance 58 Frequent (79-30%)
43 difficulty walking 58 Frequent (79-30%)
44 moderate global developmental delay 58 Frequent (79-30%)
45 tapered finger 31 HP:0001182
46 poor head control 58 Frequent (79-30%)
47 intellectual disability, profound 31 HP:0002187
48 cerebral visual impairment 31 HP:0100704
49 hyperventilation 31 HP:0002883
50 bruxism 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM:

56
Skeletal Spine:
scoliosis

Head And Neck Nose:
anteverted nares

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

Abdomen Gastrointestinal:
constipation
gastroesophageal reflux

Neurologic Central Nervous System:
myoclonus
hypsarrhythmia
infantile spasms
poor eye contact
multifocal seizures
more
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

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


constipation, myoclonus, difficulty sleeping, myoclonic seizures

MGI Mouse Phenotypes related to Epileptic Encephalopathy, Early Infantile, 2:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 9.1 CDKL5 CHRNA6 CNTNAP2 NIPBL SHTN1 USP9X

Drugs & Therapeutics for Epileptic Encephalopathy, Early Infantile, 2

Drugs for Epileptic Encephalopathy, Early Infantile, 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 11)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Anticonvulsants Phase 2
2 Neurotransmitter Agents Phase 2
3 Serotonin Uptake Inhibitors Phase 2
4 Pharmaceutical Solutions Phase 2
5 Serotonin Agents Phase 2
6 Anesthetics Phase 2
7 Central Nervous System Depressants Phase 2
8 Pregnanolone Phase 2 128-20-1
9
Serotonin Investigational, Nutraceutical Phase 2 50-67-9 5202
10
Heparin Approved, Investigational 9005-49-6 772 46507594
11 calcium heparin

Interventional clinical trials:

(show all 13)
# Name Status NCT ID Phase Drugs
1 A Double-blind, Randomized, Placebo-controlled Trial of Adjunctive Ganaxolone Treatment in Children and Young Adults With Cyclin-dependent Kinase-like 5 (CDKL5) Deficiency Disorder (CDD) Followed by Long-term Open-label Treatment Recruiting NCT03572933 Phase 3 ganaxolone;Placebo
2 A Multicenter, Open-label, Pilot Study of TAK-935 (OV935) in Patients With 15Q Duplication Syndrome or CDKL5 Deficiency Disorder (ARCADE Study) Recruiting NCT03694275 Phase 2 TAK-935
3 Fenfluramine in CKDL5 Deficiency Disorder (CDD) Recruiting NCT03861871 Phase 2 Fenfluramine Hydrochloride
4 A Phase 2, Prospective, Interventional, Open-Label, Multi-Site, Extension Study to Assess the Long-Term Safety and Tolerability of TAK-935 (OV935) as Adjunctive Therapy in Patients With Rare Epilepsy Recruiting NCT03635073 Phase 2 TAK-935
5 A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-935 as an Adjunctive Therapy in Pediatric Patients With Developmental and/or Epileptic Encephalopathies Recruiting NCT03650452 Phase 2 TAK-935;Placebo
6 A Phase 2 Randomized, Double-Masked Placebo-Controlled Crossover Safety and Tolerability Study of Ataluren for Drug Resistant Epilepsy in Patients With Nonsense Mutation CDKL5 or Dravet Syndrome Active, not recruiting NCT02758626 Phase 2 ataluren;Placebo
7 A Multicenter, Open-Label Proof-of-Concept Trial of Ganaxolone in Children With PCDH19 Female Pediatric Epilepsy and Other Rare Genetic Epilepsies Followed by 52 Week Open-Label Treatment Active, not recruiting NCT02358538 Phase 2 Ganaxolone
8 Molecular Characterization of a Cohort of 73 Patients With Infantile Spasms Syndrome Completed NCT02885389
9 Search for New Genes Involved in Molecular Etiology of Rett Syndrome Through Comparative Genomic Hybridization on DNA Microarrays Completed NCT02885090
10 Rett Syndrome Natural History: Genetic and Physical Characteristics of Rett Syndrome Completed NCT00299312
11 Rett Syndrome, MECP2 Duplication Disorder, and Rett- Related Disorders Natural History Protocol Recruiting NCT02738281
12 Biobanking of Rett Syndrome and Related Disorders Protocol Recruiting NCT02705677
13 Rett Syndrome, MECP2 Duplication, and Rett-Related Disorders Consortium, Rare Disease Clinical Research Network: Neurophysiologic Correlates Recruiting NCT03077308

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

Genetic Tests for Epileptic Encephalopathy, Early Infantile, 2

Genetic tests related to Epileptic Encephalopathy, Early Infantile, 2:

# Genetic test Affiliating Genes
1 Early Infantile Epileptic Encephalopathy 2 29

Anatomical Context for Epileptic Encephalopathy, Early Infantile, 2

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

40
Eye, Bone, Liver

Publications for Epileptic Encephalopathy, Early Infantile, 2

Articles related to Epileptic Encephalopathy, Early Infantile, 2:

(show all 24)
# Title Authors PMID Year
1
Mutational spectrum of CDKL5 in early-onset encephalopathies: a study of a large collection of French patients and review of the literature. 56 6
19793311 2009
2
Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes. 56 6
19241098 2009
3
A CDKL5 mutated child with precocious puberty. 56 6
19396824 2009
4
CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy. 56 6
18809835 2008
5
Impairment of CDKL5 nuclear localisation as a cause for severe infantile encephalopathy. 56 6
17993579 2008
6
CDKL5/STK9 is mutated in Rett syndrome variant with infantile spasms. 56 6
15689447 2005
7
Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) gene are associated with severe neurodevelopmental retardation. 56 6
15499549 2004
8
Mutations of CDKL5 cause a severe neurodevelopmental disorder with infantile spasms and mental retardation. 56 6
15492925 2004
9
Early-onset seizures due to mosaic exonic deletions of CDKL5 in a male and two females. 61 56
21293276 2011
10
The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy. 56
22872100 2013
11
Early infantile epileptic encephalopathy associated with a high voltage gated calcium channelopathy. 6
23339110 2013
12
Somatic mosaicism for a CDKL5 mutation as an epileptic encephalopathy in males. 56
20602487 2010
13
CDKL5 disruption by t(X;18) in a girl with West syndrome. 56
18564362 2008
14
The three stages of epilepsy in patients with CDKL5 mutations. 56
18266744 2008
15
Early forebrain wiring: genetic dissection using conditional Celsr3 mutant mice. 6
18487195 2008
16
Clinical and electroencephalographic features in patients with CDKL5 mutations: two new Italian cases and review of the literature. 56
18063413 2008
17
Encephalopathy and bilateral cataract in a boy with an interstitial deletion of Xp22 comprising the CDKL5 and NHS genes. 56
17256798 2007
18
CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients. 6
16611748 2006
19
Maternal origin of a novel C-terminal truncation mutation in CDKL5 causing a severe atypical form of Rett syndrome. 6
16813600 2006
20
Disruption of the serine/threonine kinase 9 gene causes severe X-linked infantile spasms and mental retardation. 56
12736870 2003
21
Mutation analysis in the MECP2 gene and genetic counselling for Rett syndrome. 56
12746405 2003
22
Seizure variables and their relationship to genotype and functional abilities in the CDKL5 disorder. 52
27770071 2016
23
Mutation in an alternative transcript of CDKL5 in a boy with early-onset seizures. 61
29444904 2018
24
Sequential Elution Interactome Analysis of the Mind Bomb 1 Ubiquitin Ligase Reveals a Novel Role in Dendritic Spine Outgrowth. 61
25931508 2015

Variations for Epileptic Encephalopathy, Early Infantile, 2

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

6 (show top 50) (show all 234) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CDKL5 NM_001323289.2(CDKL5):c.100-2A>GSNV Pathogenic 156073 rs267608423 X:18582595-18582595 X:18564475-18564475
2 CDKL5 NM_001323289.2(CDKL5):c.2376+1G>ASNV Pathogenic 156080 rs267608656 X:18638087-18638087 X:18619967-18619967
3 CDKL5 NM_001323289.2(CDKL5):c.2376+1G>CSNV Pathogenic 156081 rs267608656 X:18638087-18638087 X:18619967-18619967
4 CDKL5 NM_001323289.2(CDKL5):c.404-1G>TSNV Pathogenic 156087 rs267608474 X:18600010-18600010 X:18581890-18581890
5 CDKL5 NM_001323289.2(CDKL5):c.464-2A>GSNV Pathogenic 156090 rs267608480 X:18602381-18602381 X:18584261-18584261
6 CDKL5 NM_001323289.2(CDKL5):c.64+2deldeletion Pathogenic 156093 rs267608419 X:18525282-18525282 X:18507162-18507162
7 CDKL5 NM_001323289.2(CDKL5):c.978-2A>GSNV Pathogenic 156095 rs267608553 X:18622020-18622020 X:18603900-18603900
8 CDKL5 NM_001323289.2(CDKL5):c.99+5G>ASNV Pathogenic 156660 rs587783131 X:18528979-18528979 X:18510859-18510859
9 CDKL5 NM_001323289.2(CDKL5):c.2596C>T (p.Gln866Ter)SNV Pathogenic 156691 rs587783158 X:18646590-18646590 X:18628470-18628470
10 CDKL5 NM_001323289.2(CDKL5):c.146-1G>ASNV Pathogenic 158179 rs587783399 X:18593473-18593473 X:18575353-18575353
11 CDKL5 NM_003159.2(CDKL5):c.-253_99+?deldeletion Pathogenic 189581 X:18443725-18528974 X:18425605-18510854
12 CDKL5 NM_003159.2(CDKL5):c.-253_825+?deldeletion Pathogenic 189579 X:18443725-18613548 X:18425605-18595428
13 CDKL5 NM_003159.2(CDKL5):c.-253_977+?deldeletion Pathogenic 189580 X:18443725-18616733 X:18425605-18598613
14 CDKL5 NM_003159.2(CDKL5):c.-253_2276+?deldeletion Pathogenic 189577 X:18443725-18631395 X:18425605-18613275
15 CDKL5 NM_003159.2(CDKL5):c.-162-?_99+?deldeletion Pathogenic 189564
16 CDKL5 NM_003159.2(CDKL5):c.-162-?_145+?deldeletion Pathogenic 189562
17 CDKL5 NM_003159.2(CDKL5):c.-162-?_*85deldeletion Pathogenic 189561 X:18525055-18671749 X:18506935-18653629
18 CDKL5 NM_003159.2(CDKL5):c.65-?_99+?deldeletion Pathogenic 189596
19 CDKL5 NM_003159.2(CDKL5):c.100-?_145+?deldeletion Pathogenic 189550
20 CDKL5 NM_003159.2(CDKL5):c.146-?_*85deldeletion Pathogenic 189559 X:18593474-18671749 X:18575354-18653629
21 CDKL5 NM_003159.2(CDKL5):c.745-?_825+?deldeletion Pathogenic 189598
22 CDKL5 NM_003159.2(CDKL5):c.2377-?_*85deldeletion Pathogenic 189572 X:18643248-18671749 X:18625128-18653629
23 CDKL5 NM_003159.2(CDKL5):c.2497-?_*85deldeletion Pathogenic 189574 X:18646491-18671749 X:18628371-18653629
24 CDKL5 NM_001323289.2(CDKL5):c.-162-2A>GSNV Pathogenic 189565 rs786204973 X:18525053-18525053 X:18506933-18506933
25 CDKL5 NM_001323289.2(CDKL5):c.91A>G (p.Arg31Gly)SNV Pathogenic 189599 rs786204991 X:18528966-18528966 X:18510846-18510846
26 CDKL5 NM_001323289.2(CDKL5):c.207_213del (p.Glu70fs)deletion Pathogenic 189569 rs786204977 X:18593535-18593541 X:18575415-18575421
27 CDKL5 NM_001323289.2(CDKL5):c.275_276insAA (p.Glu93fs)insertion Pathogenic 189584 rs786204982 X:18593603-18593604 X:18575483-18575484
28 CDKL5 NM_001323289.2(CDKL5):c.283-3_290deldeletion Pathogenic 189585 rs786204983 X:18597964-18597974 X:18579844-18579854
29 CDKL5 NM_001323289.2(CDKL5):c.403+540_554+61deldeletion Pathogenic 189588 X:18598625-18602531 X:18580505-18584411
30 CDKL5 NM_001323289.2(CDKL5):c.622C>T (p.Gln208Ter)SNV Pathogenic 158186 rs587783405 X:18606141-18606141 X:18588021-18588021
31 CDKL5 NM_001323289.2(CDKL5):c.1345_1346del (p.Glu449fs)deletion Pathogenic 158177 rs587783398 X:18622389-18622390 X:18604269-18604270
32 CDKL5 NM_001323289.2(CDKL5):c.1797dup (p.Ser600fs)duplication Pathogenic 158181 rs587783401 X:18622839-18622840 X:18604719-18604720
33 CDKL5 NM_003159.2(CDKL5):c.-162-?_64+?deldeletion Pathogenic 189563
34 CDKL5 NM_001323289.2(CDKL5):c.1008_1029del (p.Ser337fs)deletion Pathogenic 189551 rs786204964 X:18622052-18622073 X:18603932-18603953
35 CDKL5 NM_001323289.2(CDKL5):c.404-1G>ASNV Pathogenic 189589 rs267608474 X:18600010-18600010 X:18581890-18581890
36 CDKL5 NM_001323289.2(CDKL5):c.458A>G (p.Asp153Gly)SNV Pathogenic 189590 rs786204985 X:18600065-18600065 X:18581945-18581945
37 CDKL5 NM_001323289.2(CDKL5):c.504_505CA[1] (p.Thr169fs)short repeat Pathogenic 189592 rs786204987 X:18602422-18602423 X:18584302-18584303
38 CDKL5 NM_001323289.2(CDKL5):c.526T>G (p.Trp176Gly)SNV Pathogenic 189594 rs587783084 X:18602445-18602445 X:18584325-18584325
39 CDKL5 NM_001323289.2(CDKL5):c.1784dup (p.Leu596fs)duplication Pathogenic 189566 rs786204974 X:18622826-18622827 X:18604706-18604707
40 CDKL5 NM_001323289.2(CDKL5):c.2103_2104AC[1] (p.His702fs)short repeat Pathogenic 189570 rs786204978 X:18627641-18627642 X:18609521-18609522
41 CDKL5 NM_001323289.2(CDKL5):c.2277-2A>GSNV Pathogenic 189571 rs786204979 X:18637985-18637985 X:18619865-18619865
42 CDKL5 NM_001323289.2(CDKL5):c.353A>G (p.Gln118Arg)SNV Pathogenic 217875 rs863225290 X:18598038-18598038 X:18579918-18579918
43 CDKL5 NM_001323289.2(CDKL5):c.2716C>T (p.Gln906Ter)SNV Pathogenic 217874 rs863225289 X:18646710-18646710 X:18628590-18628590
44 CDKL5 NM_001323289.2(CDKL5):c.747dup (p.Pro250fs)duplication Pathogenic 226116 rs875989880 X:18613467-18613468 X:18595347-18595348
45 CDKL5 NM_001323289.2(CDKL5):c.173T>A (p.Leu58Ter)SNV Pathogenic 226417 rs875989950 X:18593501-18593501 X:18575381-18575381
46 CDKL5 CDKL5, 1-BP DEL, 183Tdeletion Pathogenic 11494
47 CDKL5 CDKL5, IVSAS13, G-A, -1SNV Pathogenic 11495
48 CDKL5 NM_001323289.2(CDKL5):c.455G>T (p.Cys152Phe)SNV Pathogenic 11496 rs122460157 X:18600062-18600062 X:18581942-18581942
49 CDKL5 NM_001323289.2(CDKL5):c.525A>T (p.Arg175Ser)SNV Pathogenic 11497 rs61749700 X:18602444-18602444 X:18584324-18584324
50 CDKL5 CDKL5, 4-BP DEL, 166GAAAdeletion Pathogenic 11498

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

73 (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

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

Cellular components related to Epileptic Encephalopathy, Early Infantile, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell projection GO:0042995 8.92 USP9X SHTN1 CNTNAP2 CDKL5

Biological processes related to Epileptic Encephalopathy, Early Infantile, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 neuron projection morphogenesis GO:0048812 9.16 SHTN1 CNTNAP2
2 positive regulation of axon extension GO:0045773 8.96 SHTN1 CDKL5
3 positive regulation of neuron migration GO:2001224 8.62 SHTN1 NIPBL

Sources for Epileptic Encephalopathy, Early Infantile, 2

3 CDC
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10 dbSNP
11 DGIdb
17 EFO
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68 SNOMED-CT via HPO
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