EIEE2
MCID: EPL025
MIFTS: 50

Epileptic Encephalopathy, Early Infantile, 2 (EIEE2)

Categories: Bone diseases, Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Liver diseases, Mental diseases, Metabolic diseases, Nephrological diseases, Neuronal 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-Related Disorder 52 6
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 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 can appear as early as the first week after birth. The types of seizures change with age, and may follow a predictable pattern. The most common types are generalized tonic-clonic seizures, which involve a loss of consciousness, muscle rigidity, and convulsions; tonic seizures, which are characterized by abnormal muscle contractions; and epileptic spasms, which involve short episodes of muscle jerks. Seizures occur daily in most people with CDKL5 deficiency disorder, although they can have periods when they are seizure-free. Seizures in CDKL5 deficiency disorder are typically 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 or not achieved. 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. Most people with this condition have vision problems (cortical visual impairment). Other common features of CDKL5 deficiency disorder include repetitive hand movements (stereotypies), such as clapping, hand licking, and hand sucking; teeth 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. CDKL5 deficiency disorder was previously classified as an atypical form of Rett syndrome. These conditions have common 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 epilepsy with generalized tonic-clonic seizures and early infantile epileptic encephalopathy, and has symptoms including myoclonus, constipation and difficulty sleeping. An important gene associated with Epileptic Encephalopathy, Early Infantile, 2 is CDKL5 (Cyclin Dependent Kinase Like 5), and among its related pathways/superpathways is Nicotine addiction. The drugs Pregnanolone and Anesthetics have been mentioned in the context of this disorder. Affiliated tissues include eye, and related phenotypes are generalized tonic seizure and thick vermilion border

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 Epileptic Encephalopathy, Early Infantile, 84
Epileptic Encephalopathy, Early Infantile, 86 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 84)
# Related Disease Score Top Affiliating Genes
1 epilepsy with generalized tonic-clonic seizures 31.8 GABRA1 CDKL5
2 early infantile epileptic encephalopathy 31.7 GABRA1 CNTNAP2 CDKL5
3 benign neonatal seizures 31.7 GABRA1 CDKL5
4 pitt-hopkins syndrome 31.5 CNTNAP2 CDKL5
5 epileptic encephalopathy, early infantile, 6 31.3 GABRA1 CNTNAP2 CDKL5
6 benign familial neonatal epilepsy 31.3 GABRA1 CDKL5
7 infancy electroclinical syndrome 31.2 GABRA1 CDKL5
8 electroclinical syndrome 31.2 GABRA1 CDKL5
9 childhood electroclinical syndrome 31.2 GABRA1 CDKL5
10 neonatal period electroclinical syndrome 31.1 GABRA1 CDKL5
11 benign familial infantile epilepsy 31.0 GABRA1 CDKL5
12 lennox-gastaut syndrome 30.8 GABRA1 CDKL5
13 benign epilepsy with centrotemporal spikes 30.8 GABRA1 CNTNAP2 CDKL5
14 childhood absence epilepsy 30.8 GABRA1 CNTNAP2 CDKL5
15 autism 30.7 NSD1 GABRA1 CNTNAP2 CDKL5
16 west syndrome 29.3 GABRA1 CNTNAP2 CDKL5
17 early myoclonic encephalopathy 11.5
18 microcephaly 11.5
19 mental retardation, autosomal dominant 20 11.3
20 angelman syndrome 11.2
21 focal epilepsy 11.2
22 bruxism 11.2
23 amyotrophic lateral sclerosis 1 11.2
24 epileptic encephalopathy, early infantile, 4 11.2
25 methylmalonic acidemia 11.2
26 sturge-weber syndrome 11.0
27 mowat-wilson syndrome 11.0
28 epilepsy, myoclonic juvenile 11.0
29 peho syndrome 11.0
30 epileptic encephalopathy, early infantile, 9 11.0
31 lubs x-linked mental retardation syndrome 11.0
32 epilepsy, idiopathic generalized 11.0
33 nicolaides-baraitser syndrome 11.0
34 encephalopathy due to defective mitochondrial and peroxisomal fission 1 11.0
35 epileptic encephalopathy, early infantile, 13 11.0
36 epileptic encephalopathy, early infantile, 14 11.0
37 specific developmental disorder 11.0
38 pervasive developmental disorder 11.0
39 generalized epilepsy with febrile seizures plus 11.0
40 christianson syndrome 11.0
41 congenital nervous system abnormality 11.0
42 partial motor epilepsy 11.0
43 gait apraxia 11.0
44 hypotonia 10.6
45 alacrima, achalasia, and mental retardation syndrome 10.4
46 rett syndrome 10.3
47 epilepsy 10.3
48 myoclonus 10.2
49 visual epilepsy 10.2
50 encephalopathy 10.2

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 58)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 generalized tonic seizure 31 hallmark (90%) HP:0010818
2 thick vermilion border 58 31 frequent (33%) Frequent (79-30%) HP:0012471
3 prominent forehead 58 31 frequent (33%) Frequent (79-30%) HP:0011220
4 everted lower lip vermilion 58 31 frequent (33%) Frequent (79-30%) HP:0000232
5 growth delay 58 31 frequent (33%) Frequent (79-30%) HP:0001510
6 impaired pain sensation 58 31 frequent (33%) Frequent (79-30%) HP:0007328
7 deeply set eye 58 31 frequent (33%) Frequent (79-30%) HP:0000490
8 deep philtrum 58 31 frequent (33%) Frequent (79-30%) HP:0002002
9 broad forehead 58 31 frequent (33%) Frequent (79-30%) HP:0000337
10 severe global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0011344
11 moderate global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0011343
12 infantile spasms 58 31 frequent (33%) Frequent (79-30%) HP:0012469
13 poor eye contact 58 31 frequent (33%) Frequent (79-30%) HP:0000817
14 poor head control 58 31 frequent (33%) Frequent (79-30%) HP:0002421
15 delayed gross motor development 58 31 frequent (33%) Frequent (79-30%) HP:0002194
16 focal-onset seizure 58 31 frequent (33%) Frequent (79-30%) HP:0007359
17 difficulty walking 58 31 frequent (33%) Frequent (79-30%) HP:0002355
18 bruxism 58 31 frequent (33%) Frequent (79-30%) HP:0003763
19 multifocal epileptiform discharges 58 31 frequent (33%) Frequent (79-30%) HP:0010841
20 inappropriate laughter 58 31 frequent (33%) Frequent (79-30%) HP:0000748
21 abnormal muscle tone 58 31 frequent (33%) Frequent (79-30%) HP:0003808
22 sleep-wake cycle disturbance 58 31 frequent (33%) Frequent (79-30%) HP:0006979
23 stereotypical hand wringing 58 31 frequent (33%) Frequent (79-30%) HP:0012171
24 broad proximal phalanges of the hand 58 31 frequent (33%) Frequent (79-30%) HP:0009852
25 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
26 kyphosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002808
27 high forehead 58 31 occasional (7.5%) Occasional (29-5%) HP:0000348
28 hallux valgus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001822
29 synophrys 58 31 occasional (7.5%) Occasional (29-5%) HP:0000664
30 narrow forehead 58 31 occasional (7.5%) Occasional (29-5%) HP:0000341
31 functional respiratory abnormality 58 31 occasional (7.5%) Occasional (29-5%) HP:0002795
32 eeg with generalized slow activity 31 very rare (1%) HP:0010845
33 global developmental delay 31 HP:0001263
34 muscular hypotonia 31 HP:0001252
35 anteverted nares 31 HP:0000463
36 developmental regression 31 HP:0002376
37 gastroesophageal reflux 31 HP:0002020
38 stereotypy 31 HP:0000733
39 gait disturbance 58 Frequent (79-30%)
40 thick lower lip vermilion 31 HP:0000179
41 myoclonus 31 HP:0001336
42 constipation 31 HP:0002019
43 small hand 31 HP:0200055
44 tapered finger 31 HP:0001182
45 short foot 31 HP:0001773
46 short palm 31 HP:0004279
47 intellectual disability, profound 31 HP:0002187
48 generalized hypotonia 31 HP:0001290
49 inability to walk 31 HP:0002540
50 cerebral visual impairment 31 HP:0100704

Symptoms via clinical synopsis from OMIM:

56
Skeletal Spine:
scoliosis

Abdomen Gastrointestinal:
gastroesophageal reflux
constipation

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

Head And Neck Nose:
anteverted nares

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

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


myoclonus, constipation, 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 9.17 CDKL5 CHRNA6 CNTNAP2 GABRA1 NIPBL SHTN1

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 9)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Pregnanolone Phase 3 128-20-1
2 Anesthetics Phase 3
3 Pharmaceutical Solutions Phase 2
4 Serotonin Uptake Inhibitors Phase 2
5 Neurotransmitter Agents Phase 2
6 Anticonvulsants Phase 2
7
Serotonin Investigational, Nutraceutical Phase 2 50-67-9 5202
8
Heparin Approved, Investigational 9005-49-6 46507594 772
9 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 Active, not 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 CDKL5

Anatomical Context for Epileptic Encephalopathy, Early Infantile, 2

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

40
Eye

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. 6 56
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. 6 56
18809835 2008
5
Impairment of CDKL5 nuclear localisation as a cause for severe infantile encephalopathy. 6 56
17993579 2008
6
CDKL5/STK9 is mutated in Rett syndrome variant with infantile spasms. 56 6
15689447 2005
7
Mutations of CDKL5 cause a severe neurodevelopmental disorder with infantile spasms and mental retardation. 56 6
15492925 2004
8
Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) gene are associated with severe neurodevelopmental retardation. 6 56
15499549 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 334) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CDKL5 NM_001323289.2(CDKL5):c.2022del (p.Phe675fs)deletion Pathogenic 408123 rs1060501860 X:18627007-18627007 X:18608887-18608887
2 CDKL5 NM_001323289.2(CDKL5):c.1684_1687del (p.Thr562fs)deletion Pathogenic 434665 rs1555952101 X:18622726-18622729 X:18604606-18604609
3 CDKL5 NM_001323289.2(CDKL5):c.2359_2363del (p.Lys787fs)deletion Pathogenic 437405 rs1555954078 X:18638067-18638071 X:18619947-18619951
4 CDKL5 NM_001323289.2(CDKL5):c.2828_2829del (p.Arg943fs)deletion Pathogenic 441534 rs1555955290 X:18646821-18646822 X:18628701-18628702
5 CDKL5 NM_001323289.2(CDKL5):c.1246G>T (p.Glu416Ter)SNV Pathogenic 464808 rs1555951991 X:18622290-18622290 X:18604170-18604170
6 CDKL5 NM_001323289.2(CDKL5):c.244del (p.Arg82fs)deletion Pathogenic 464813 rs1555949041 X:18593572-18593572 X:18575452-18575452
7 CDKL5 NM_001323289.2(CDKL5):c.1519C>T (p.Gln507Ter)SNV Pathogenic 464809 rs1555952052 X:18622563-18622563 X:18604443-18604443
8 CDKL5 NM_001323289.2(CDKL5):c.2345C>A (p.Ser782Ter)SNV Pathogenic 464812 rs1555954074 X:18638055-18638055 X:18619935-18619935
9 CDKL5 NM_001323289.2(CDKL5):c.1345G>T (p.Glu449Ter)SNV Pathogenic 434663 rs1555952015 X:18622389-18622389 X:18604269-18604269
10 CDKL5 NM_001323289.2(CDKL5):c.453del (p.Cys152fs)deletion Pathogenic 488477 rs1555949763 X:18600060-18600060 X:18581940-18581940
11 CDKL5 NM_001323289.2(CDKL5):c.786C>A (p.Tyr262Ter)SNV Pathogenic 489166 rs1555951146 X:18613509-18613509 X:18595389-18595389
12 CDKL5 NC_000023.11:g.(?_18564457)_(18581970_?)deldeletion Pathogenic 533400 X:18582577-18600090 X:18564457-18581970
13 CDKL5 NM_001323289.2(CDKL5):c.198_199TC[1] (p.Leu67fs)short repeat Pathogenic 533386 rs1555949011 X:18593525-18593526 X:18575405-18575406
14 CDKL5 NM_001323289.2(CDKL5):c.508G>T (p.Glu170Ter)SNV Pathogenic 533384 rs1555950066 X:18602427-18602427 X:18584307-18584307
15 CDKL5 NM_001323289.2(CDKL5):c.614_617dup (p.Asp206fs)duplication Pathogenic 533389 rs1555950465 X:18606131-18606132 X:18588011-18588012
16 CDKL5 NM_001323289.2(CDKL5):c.725del (p.Pro242fs)deletion Pathogenic 533390 rs1555950494 X:18606243-18606243 X:18588123-18588123
17 CDKL5 NM_001323289.2(CDKL5):c.2452_2459del (p.Pro818fs)deletion Pathogenic 548518 rs1555954737 X:18643321-18643328 X:18625201-18625208
18 CDKL5 NM_001323289.2(CDKL5):c.868C>T (p.Gln290Ter)SNV Pathogenic 560971 rs1569218019 X:18616624-18616624 X:18598504-18598504
19 CDKL5 NM_001323289.2(CDKL5):c.282+1G>TSNV Pathogenic 582020 rs1569213054 X:18593611-18593611 X:18575491-18575491
20 CDKL5 NM_001323289.2(CDKL5):c.583T>G (p.Trp195Gly)SNV Pathogenic 567323 rs1569215594 X:18606102-18606102 X:18587982-18587982
21 CDKL5 NM_001323289.2(CDKL5):c.638G>A (p.Gly213Glu)SNV Pathogenic 577127 rs1569215629 X:18606157-18606157 X:18588037-18588037
22 CDKL5 NC_000023.10:g.(?_17393861)_(18671684_?)deldeletion Pathogenic 584356 X:17393861-18671684
23 CDKL5 NM_001323289.2(CDKL5):c.2142del (p.Tyr716fs)deletion Pathogenic 576176 rs1569220925 X:18627680-18627680 X:18609560-18609560
24 CDKL5 NM_001323289.2(CDKL5):c.2326_2327del (p.Lys776fs)deletion Pathogenic 652635 X:18638036-18638037 X:18619916-18619917
25 CDKL5 NM_001323289.2(CDKL5):c.2345C>G (p.Ser782Ter)SNV Pathogenic 662018 X:18638055-18638055 X:18619935-18619935
26 CDKL5 NC_000023.11:g.(?_18506933)_(18653564_?)deldeletion Pathogenic 662287 X:18525053-18671684 X:18506933-18653564
27 CDKL5 NM_001323289.2(CDKL5):c.2785C>T (p.Gln929Ter)SNV Pathogenic 648838 X:18646779-18646779 X:18628659-18628659
28 CDKL5 NM_001323289.2(CDKL5):c.364G>A (p.Ala122Thr)SNV Pathogenic 803716 X:18598049-18598049 X:18579929-18579929
29 CDKL5 NM_001323289.2(CDKL5):c.386del (p.Asn129fs)deletion Pathogenic 803717 X:18598070-18598070 X:18579950-18579950
30 CDKL5 NM_001323289.2(CDKL5):c.425T>G (p.Leu142Ter)SNV Pathogenic 803718 X:18600032-18600032 X:18581912-18581912
31 CDKL5 NM_001323289.2(CDKL5):c.1742dup (p.His581fs)duplication Pathogenic 803722 X:18622785-18622786 X:18604665-18604666
32 CDKL5 NM_001323289.2(CDKL5):c.1816C>T (p.Gln606Ter)SNV Pathogenic 803723 X:18622860-18622860 X:18604740-18604740
33 CDKL5 NM_001323289.2(CDKL5):c.2480C>G (p.Ser827Ter)SNV Pathogenic 803724 X:18643351-18643351 X:18625231-18625231
34 CDKL5 NM_001323289.2(CDKL5):c.1431_1435dup (p.Ser479fs)duplication Pathogenic 803720 X:18622474-18622475 X:18604354-18604355
35 CDKL5 NM_001323289.2(CDKL5):c.898_899del (p.Gln300fs)deletion Pathogenic 813762 X:18616654-18616655 X:18598534-18598535
36 CDKL5 NM_001323289.2(CDKL5):c.2276+1G>ASNV Pathogenic 813729 X:18631396-18631396 X:18613276-18613276
37 CDKL5 NC_000023.11:g.(?_18595328)_(18595448_?)deldeletion Pathogenic 831965 X:18613448-18613568
38 CDKL5 NC_000023.11:g.(?_18628351)_(18628607_?)deldeletion Pathogenic 832153 X:18646471-18646727
39 CDKL5 NC_000023.11:g.(?_18506933)_(18510874_?)deldeletion Pathogenic 830999 X:18525053-18528994
40 CDKL5 NC_000023.11:g.(?_18506933)_(18604888_?)deldeletion Pathogenic 831097 X:18525053-18623008
41 CDKL5 NM_001323289.2(CDKL5):c.154G>T (p.Glu52Ter)SNV Pathogenic 861338 X:18593482-18593482 X:18575362-18575362
42 CDKL5 NM_001323289.2(CDKL5):c.877_881dup (p.His294fs)duplication Pathogenic 845526 X:18616632-18616633 X:18598512-18598513
43 CDKL5 NM_001323289.2(CDKL5):c.1485dup (p.Lys496fs)duplication Pathogenic 838071 X:18622527-18622528 X:18604407-18604408
44 CDKL5 NM_001323289.2(CDKL5):c.1755_1756del (p.Ser586fs)deletion Pathogenic 856634 X:18622798-18622799 X:18604678-18604679
45 CDKL5 NM_001323289.2(CDKL5):c.1883del (p.Ser628fs)deletion Pathogenic 840609 X:18622927-18622927 X:18604807-18604807
46 CDKL5 NM_001323289.2(CDKL5):c.2197_2204dup (p.Arg735fs)duplication Pathogenic 857515 X:18631314-18631315 X:18613194-18613195
47 CDKL5 NM_001323289.2(CDKL5):c.495dup (p.Ala166fs)duplication Pathogenic 870173 X:18602413-18602414 X:18584293-18584294
48 CDKL5 NM_001323289.2(CDKL5):c.1486A>T (p.Lys496Ter)SNV Pathogenic 870174 X:18622530-18622530 X:18604410-18604410
49 CDKL5 NM_001323289.2(CDKL5):c.1852_1853insT (p.Asp618fs)insertion Pathogenic 870169 X:18622896-18622897 X:18604776-18604777
50 CDKL5 NM_001323289.2(CDKL5):c.2182del (p.His728fs)deletion Pathogenic 870175 X:18631300-18631300 X:18613180-18613180

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

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

# Super pathways Score Top Affiliating Genes
1 10.23 GABRA1 CHRNA6

GO Terms for Epileptic Encephalopathy, Early Infantile, 2

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 9.32 SHTN1 CNTNAP2
2 regulation of postsynaptic membrane potential GO:0060078 9.26 GABRA1 CHRNA6
3 nervous system process GO:0050877 9.16 GABRA1 CHRNA6
4 positive regulation of axon extension GO:0045773 8.96 SHTN1 CDKL5
5 positive regulation of neuron migration GO:2001224 8.62 SHTN1 NIPBL

Molecular functions related to Epileptic Encephalopathy, Early Infantile, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 neurotransmitter receptor activity GO:0030594 8.96 GABRA1 CHRNA6
2 extracellular ligand-gated ion channel activity GO:0005230 8.62 GABRA1 CHRNA6

Sources for Epileptic Encephalopathy, Early Infantile, 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....