CDKL5
MCID: CDK006
MIFTS: 30

Cdkl5 Deficiency Disorder (CDKL5)

Categories: Rare diseases

Aliases & Classifications for Cdkl5 Deficiency Disorder

MalaCards integrated aliases for Cdkl5 Deficiency Disorder:

Name: Cdkl5 Deficiency Disorder 20 43
Cdkl5-Related Disorder 20 6
Cdkl5 Deficiency 20 43
Cdkl5 Disorder 20 43
X-Linked Dominant Infantile Spasm Syndrome-2 20
Early Infantile Epileptic Encephalopathy 2 43
Early Infantile Epileptic Encephalopathy-2 20
Cdkl5-Related Epileptic Encephalopathy 43
Cdkl5-Related Epilepsy 43
Cdkl5 Encephalopathy 43
Cdkl5 20

Classifications:



Summaries for Cdkl5 Deficiency Disorder

MedlinePlus Genetics : 43 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 : Cdkl5 Deficiency Disorder, also known as cdkl5-related disorder, is related to early infantile epileptic encephalopathy and developmental and epileptic encephalopathy 2. An important gene associated with Cdkl5 Deficiency Disorder is CDKL5 (Cyclin Dependent Kinase Like 5). The drugs Pregnanolone and Anesthetics have been mentioned in the context of this disorder. Affiliated tissues include eye and cortex, and related phenotypes are generalized tonic seizure and thick vermilion border

GARD : 20 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.

Wikipedia : 73 CDKL5 is a gene that provides instructions for making a protein called cyclin-dependent kinase-like 5... more...

Related Diseases for Cdkl5 Deficiency Disorder

Diseases related to Cdkl5 Deficiency Disorder via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 105)
# Related Disease Score Top Affiliating Genes
1 early infantile epileptic encephalopathy 11.2
2 developmental and epileptic encephalopathy 2 11.2
3 retinoschisis 1, x-linked, juvenile 11.0
4 juvenile retinoschisis 11.0
5 early myoclonic encephalopathy 11.0
6 microcephaly 11.0
7 angelman syndrome 11.0
8 autism 11.0
9 developmental and epileptic encephalopathy 1 11.0
10 methylmalonic acidemia 11.0
11 amyotrophic lateral sclerosis 1 10.9
12 nicolaides-baraitser syndrome 10.9
13 focal epilepsy 10.9
14 bruxism 10.9
15 fundus dystrophy 10.9
16 pyruvate dehydrogenase e1-alpha deficiency 10.8
17 pitt-hopkins syndrome 10.8
18 mental retardation, autosomal dominant 20 10.8
19 benign neonatal seizures 10.8
20 epilepsy with generalized tonic-clonic seizures 10.8
21 sturge-weber syndrome 10.8
22 mowat-wilson syndrome 10.8
23 epilepsy, myoclonic juvenile 10.8
24 peho syndrome 10.8
25 developmental and epileptic encephalopathy 9 10.8
26 lubs x-linked mental retardation syndrome 10.8
27 fragile x syndrome 10.8
28 epilepsy, idiopathic generalized 10.8
29 developmental and epileptic encephalopathy 4 10.8
30 encephalopathy due to defective mitochondrial and peroxisomal fission 1 10.8
31 developmental and epileptic encephalopathy 14 10.8
32 myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency 10.8
33 lennox-gastaut syndrome 10.8
34 neonatal period electroclinical syndrome 10.8
35 infancy electroclinical syndrome 10.8
36 childhood electroclinical syndrome 10.8
37 specific developmental disorder 10.8
38 pervasive developmental disorder 10.8
39 benign familial infantile epilepsy 10.8
40 generalized epilepsy with febrile seizures plus 10.8
41 christianson syndrome 10.8
42 gene duplication disease 10.8
43 benign familial neonatal epilepsy 10.8
44 disease of mental health 10.8
45 childhood absence epilepsy 10.8
46 congenital nervous system abnormality 10.8
47 benign epilepsy with centrotemporal spikes 10.8
48 gait apraxia 10.8
49 x-linked congenital retinoschisis 10.8
50 encephalopathy 10.5

Graphical network of the top 20 diseases related to Cdkl5 Deficiency Disorder:



Diseases related to Cdkl5 Deficiency Disorder

Symptoms & Phenotypes for Cdkl5 Deficiency Disorder

Human phenotypes related to Cdkl5 Deficiency Disorder:

31 (show all 31)
# Description HPO Frequency HPO Source Accession
1 generalized tonic seizure 31 hallmark (90%) HP:0010818
2 thick vermilion border 31 frequent (33%) HP:0012471
3 prominent forehead 31 frequent (33%) HP:0011220
4 everted lower lip vermilion 31 frequent (33%) HP:0000232
5 growth delay 31 frequent (33%) HP:0001510
6 impaired pain sensation 31 frequent (33%) HP:0007328
7 deeply set eye 31 frequent (33%) HP:0000490
8 deep philtrum 31 frequent (33%) HP:0002002
9 broad forehead 31 frequent (33%) HP:0000337
10 severe global developmental delay 31 frequent (33%) HP:0011344
11 moderate global developmental delay 31 frequent (33%) HP:0011343
12 infantile spasms 31 frequent (33%) HP:0012469
13 poor eye contact 31 frequent (33%) HP:0000817
14 poor head control 31 frequent (33%) HP:0002421
15 delayed gross motor development 31 frequent (33%) HP:0002194
16 focal-onset seizure 31 frequent (33%) HP:0007359
17 difficulty walking 31 frequent (33%) HP:0002355
18 bruxism 31 frequent (33%) HP:0003763
19 multifocal epileptiform discharges 31 frequent (33%) HP:0010841
20 inappropriate laughter 31 frequent (33%) HP:0000748
21 abnormal muscle tone 31 frequent (33%) HP:0003808
22 sleep-wake cycle disturbance 31 frequent (33%) HP:0006979
23 stereotypical hand wringing 31 frequent (33%) HP:0012171
24 broad proximal phalanges of the hand 31 frequent (33%) HP:0009852
25 scoliosis 31 occasional (7.5%) HP:0002650
26 kyphosis 31 occasional (7.5%) HP:0002808
27 high forehead 31 occasional (7.5%) HP:0000348
28 hallux valgus 31 occasional (7.5%) HP:0001822
29 synophrys 31 occasional (7.5%) HP:0000664
30 narrow forehead 31 occasional (7.5%) HP:0000341
31 abnormal respiratory system physiology 31 occasional (7.5%) HP:0002795

Drugs & Therapeutics for Cdkl5 Deficiency Disorder

Drugs for Cdkl5 Deficiency Disorder (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Pregnanolone Investigational Phase 3 128-20-1 31402
2 Anesthetics Phase 3
3 Anticonvulsants Phase 2

Interventional clinical trials:


# 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 Active, not 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) Completed NCT03694275 Phase 2 TAK-935
3 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
4 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
5 Orphan Disease Center CDKL5 Deficiency Disorder International Patient Registry Recruiting NCT04486768
6 Expanded Access With Adjunctive Ganaxolone Treatment in Children and Young Adults With Cyclin Dependent Kinase-like 5 Deficiency Disorder Available NCT04678479 Ganaxolone

Search NIH Clinical Center for Cdkl5 Deficiency Disorder

Genetic Tests for Cdkl5 Deficiency Disorder

Anatomical Context for Cdkl5 Deficiency Disorder

MalaCards organs/tissues related to Cdkl5 Deficiency Disorder:

40
Eye, Cortex

Publications for Cdkl5 Deficiency Disorder

Articles related to Cdkl5 Deficiency Disorder:

(show all 47)
# Title Authors PMID Year
1
Seizure variables and their relationship to genotype and functional abilities in the CDKL5 disorder. 20
27770071 2016
2
Clinical manifestations and epilepsy treatment in Japanese patients with pathogenic CDKL5 variants. 61
33436160 2021
3
Highly Purified Cannabidiol for Epilepsy Treatment: A Systematic Review of Epileptic Conditions Beyond Dravet Syndrome and Lennox-Gastaut Syndrome. 61
33754312 2021
4
Ataluren for drug-resistant epilepsy in nonsense variant-mediated Dravet syndrome and CDKL5 deficiency disorder. 61
33538404 2021
5
Generation and characterization of human induced pluripotent stem cells (iPSCs) from three male and three female patients with CDKL5 Deficiency Disorder (CDD). 61
33714067 2021
6
A GABAB receptor antagonist rescues functional and structural impairments in the perirhinal cortex of a mouse model of CDKL5 deficiency disorder. 61
33621640 2021
7
CDKL5 deficiency in forebrain glutamatergic neurons results in recurrent spontaneous seizures. 61
33400301 2021
8
Exploring quality of life in individuals with a severe developmental and epileptic encephalopathy, CDKL5 Deficiency Disorder. 61
33341033 2021
9
In vivo magnetic resonance spectroscopy in the brain of Cdkl5 null mice reveals a metabolic profile indicative of mitochondrial dysfunctions. 61
33448385 2021
10
X-linked cellular mosaicism underlies age-dependent occurrence of seizure-like events in mouse models of CDKL5 deficiency disorder. 61
33197557 2021
11
CDKL5 mutations may mimic Pitt-Hopkins syndrome phenotype. 61
33220470 2021
12
Exploring genotype-phenotype relationships in the CDKL5 deficiency disorder using an international dataset. 61
33047306 2021
13
Seizures in Mouse Models of Rare Neurodevelopmental Disorders. 61
32059984 2020
14
Structural Bases of Atypical Whisker Responses in a Mouse Model of CDKL5 Deficiency Disorder. 61
31472213 2020
15
Aged heterozygous Cdkl5 mutant mice exhibit spontaneous epileptic spasms. 61
32585155 2020
16
Dopaminergic loss of cyclin-dependent kinase-like 5 recapitulates methylphenidate-remediable hyperlocomotion in mouse model of CDKL5 deficiency disorder. 61
32588892 2020
17
Comparison of Core Features in Four Developmental Encephalopathies in the Rett Natural History Study. 61
32472944 2020
18
Cyclin-dependent-like kinase 5 is required for pain signaling in human sensory neurons and mouse models. 61
32641489 2020
19
Pharmacotherapy with sertraline rescues brain development and behavior in a mouse model of CDKL5 deficiency disorder. 61
31469994 2020
20
The green tea polyphenol epigallocatechin-3-gallate (EGCG) restores CDKL5-dependent synaptic defects in vitro and in vivo. 61
32032735 2020
21
Increased DNA Damage and Apoptosis in CDKL5-Deficient Neurons. 61
32002787 2020
22
Expanding the phenotype of the CDKL5 deficiency disorder: Are seizures mandatory? 61
32034940 2020
23
Proof-of-concept for a gene replacement approach to CDKL5 deficiency disorder. 61
32203572 2020
24
Pregnenolone and pregnenolone-methyl-ether rescue neuronal defects caused by dysfunctional CLIP170 in a neuronal model of CDKL5 Deficiency Disorder. 61
31794725 2020
25
CDKL5 Deficiency Disorder-A Complex Epileptic Encephalopathy. 61
32079229 2020
26
Cyclin-Dependent Kinase-Like 5 (CDKL5): Possible Cellular Signalling Targets and Involvement in CDKL5 Deficiency Disorder. 61
32587608 2020
27
Evoked Potentials and EEG Analysis in Rett Syndrome and Related Developmental Encephalopathies: Towards a Biomarker for Translational Research. 61
32547374 2020
28
Aberrant mitochondrial function in patient-derived neural cells from CDKL5 deficiency disorder and Rett syndrome. 61
31518399 2019
29
Rett Syndrome and CDKL5 Deficiency Disorder: From Bench to Clinic. 61
31618813 2019
30
CDKL5 deficiency predisposes neurons to cell death through the deregulation of SMAD3 signaling. 61
30793413 2019
31
Site-specific abnormalities in the visual system of a mouse model of CDKL5 deficiency disorder. 61
31108505 2019
32
Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review. 61
30928302 2019
33
Microtubules: A Key to Understand and Correct Neuronal Defects in CDKL5 Deficiency Disorder? 61
31438497 2019
34
Severity Assessment in CDKL5 Deficiency Disorder. 61
31147226 2019
35
CDKL5 deficiency disorder: Relationship between genotype, epilepsy, cortical visual impairment, and development. 61
31313283 2019
36
Reflex Seizures in a Patient with CDKL5 Deficiency Disorder. 61
31030687 2019
37
Altered NMDAR signaling underlies autistic-like features in mouse models of CDKL5 deficiency disorder. 61
31201320 2019
38
Clinical evolution and epilepsy outcome in three patients with CDKL5-related developmental encephalopathy. 61
31225800 2019
39
AMPA Receptor Dysregulation and Therapeutic Interventions in a Mouse Model of CDKL5 Deficiency Disorder. 61
30952813 2019
40
Cannabis for refractory epilepsy in children: A review focusing on CDKL5 Deficiency Disorder. 61
30771550 2019
41
A framework for understanding quality of life domains in individuals with the CDKL5 deficiency disorder. 61
30561084 2019
42
Functional and Structural Impairments in the Perirhinal Cortex of a Mouse Model of CDKL5 Deficiency Disorder Are Rescued by a TrkB Agonist. 61
31114483 2019
43
Rescue of prepulse inhibition deficit and brain mitochondrial dysfunction by pharmacological stimulation of the central serotonin receptor 7 in a mouse model of CDKL5 Deficiency Disorder. 61
30326240 2019
44
Chemical genetic identification of CDKL5 substrates reveals its role in neuronal microtubule dynamics. 61
30266824 2018
45
Vagus nerve stimulation for the treatment of refractory epilepsy in the CDKL5 Deficiency Disorder. 61
30071384 2018
46
Open-label use of highly purified CBD (Epidiolex®) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. 61
30006259 2018
47
Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory. 61
29702698 2018

Variations for Cdkl5 Deficiency Disorder

ClinVar genetic disease variations for Cdkl5 Deficiency Disorder:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CDKL5 NM_001323289.2(CDKL5):c.2760_2761CA[1] (p.Thr921fs) Microsatellite Likely pathogenic 870574 GRCh37: X:18646754-18646755
GRCh38: X:18628634-18628635

Expression for Cdkl5 Deficiency Disorder

Search GEO for disease gene expression data for Cdkl5 Deficiency Disorder.

Pathways for Cdkl5 Deficiency Disorder

GO Terms for Cdkl5 Deficiency Disorder

Sources for Cdkl5 Deficiency Disorder

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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