MCID: ENC021
MIFTS: 32

Encephalopathy, Neonatal Severe

Categories: Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Encephalopathy, Neonatal Severe

MalaCards integrated aliases for Encephalopathy, Neonatal Severe:

Name: Encephalopathy, Neonatal Severe 54 13
Severe Neonatal-Onset Encephalopathy with Microcephaly 56 29
Encephalopathy, Neonatal Severe, Due to Mecp2 Mutations 71
Severe Congenital Encephalopathy Due to Mecp2 Mutation 56
Ens-Mecp2 71

Characteristics:

Orphanet epidemiological data:

56
severe neonatal-onset encephalopathy with microcephaly
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

54
Miscellaneous:
onset at birth
death usually within first 2 years of life
mecp2 mutations are those found in females with rett syndrome

Inheritance:
x-linked recessive


HPO:

32
encephalopathy, neonatal severe:
Onset and clinical course congenital onset
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 56  
Rare neurological diseases


Summaries for Encephalopathy, Neonatal Severe

OMIM : 54
The MECP2 gene is mutated in Rett syndrome (RTT; 312750), a severe neurodevelopmental disorder that almost always occurs in females. Although it was first thought that MECP2 mutations causing Rett syndrome were lethal in males, later reports identified a severe neonatal encephalopathy in surviving male sibs of patients with Rett syndrome. Since then, additional reports have confirmed a severe phenotype in males with RTT-associated MECP2 mutations (Moog et al., 2003; Villard, 2007). Males with non-RTT mutations in the MECP2 gene can demonstrate a wide variety of phenotypes: see also nonspecific X-linked mental retardation, X-linked mental retardation with spasticity (300055), and X-linked mental retardation due to increased dosage of the MECP2 gene (300260). (300673)

MalaCards based summary : Encephalopathy, Neonatal Severe, also known as severe neonatal-onset encephalopathy with microcephaly, is related to encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities and mecp2-related severe neonatal encephalopathy, and has symptoms including failure to thrive, myoclonus and intellectual disability, severe. An important gene associated with Encephalopathy, Neonatal Severe is MECP2 (Methyl-CpG Binding Protein 2). The drugs Tocopherol and Vitamin C have been mentioned in the context of this disorder. Affiliated tissues include brain and heart.

UniProtKB/Swiss-Prot : 71 Encephalopathy, neonatal severe, due to MECP2 mutations: A neurodevelopmental disorder characterized by severe neonatal encephalopathy, developmental delay, mental retardation, microcephaly, seizures. Additional features include respiratory insufficiency and central hypoventilation, gastroesophageal reflux, axial hypotonia, hyperreflexia and dyskinetic movements.

Related Diseases for Encephalopathy, Neonatal Severe

Diseases in the Encephalopathy, Neonatal Severe family:

Mecp2-Related Severe Neonatal Encephalopathy

Diseases related to Encephalopathy, Neonatal Severe via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities 12.0
2 mecp2-related severe neonatal encephalopathy 11.3

Symptoms & Phenotypes for Encephalopathy, Neonatal Severe

Symptoms via clinical synopsis from OMIM:

54

Growth- Other:
failure to thrive

Abdomen- Gastroin testinal:
poor feeding
gastroesophageal reflux

Head And Neck- Head:
microcephaly, progressive

Neurologic- Central Nervous System:
myoclonus
hyperreflexia
eeg abnormalities
seizures
axial hypotonia
more
Respiratory:
apnea
respiratory insufficiency
central hypoventilation

Neurologic- Behavioral Psychiatric Manifestations:
stereotypical movements


Clinical features from OMIM:

300673

Human phenotypes related to Encephalopathy, Neonatal Severe:

32 (show all 18)
id Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 myoclonus 32 HP:0001336
3 intellectual disability, severe 32 HP:0010864
4 hyperreflexia 32 HP:0001347
5 seizures 32 HP:0001250
6 polymicrogyria 32 HP:0002126
7 encephalopathy 32 HP:0001298
8 global developmental delay 32 HP:0001263
9 rigidity 32 HP:0002063
10 apnea 32 HP:0002104
11 gastroesophageal reflux 32 HP:0002020
12 respiratory insufficiency 32 HP:0002093
13 feeding difficulties in infancy 32 HP:0008872
14 progressive microcephaly 32 HP:0000253
15 central hypoventilation 32 HP:0007110
16 eeg abnormality 32 HP:0002353
17 intellectual disability, progressive 32 HP:0006887
18 muscular hypotonia of the trunk 32 HP:0008936

UMLS symptoms related to Encephalopathy, Neonatal Severe:


myoclonus, seizures, limb rigidity

Drugs & Therapeutics for Encephalopathy, Neonatal Severe

Drugs for Encephalopathy, Neonatal Severe (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 50)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Tocopherol Approved, Nutraceutical Phase 4
2
Vitamin C Approved, Nutraceutical Phase 4 50-81-7 5785 54670067
3
Vitamin E Approved, Nutraceutical, Vet_approved Phase 4 59-02-9 14985
4 Antioxidants Phase 4,Phase 3,Phase 1
5
Bilirubin Phase 4 635-65-4 5280352
6 Pharmaceutical Solutions Phase 4,Phase 3,Phase 1
7 Protective Agents Phase 4,Phase 3,Phase 2,Phase 1
8 Micronutrients Phase 4
9 Tocopherols Phase 4
10 Tocotrienols Phase 4
11 Trace Elements Phase 4
12 Vitamins Phase 4
13 Tocotrienol Investigational, Nutraceutical Phase 4 6829-55-6
14
Benzocaine Approved Phase 3 1994-09-7, 94-09-7 2337
15
Magnesium Sulfate Approved, Vet_approved Phase 2, Phase 3 7487-88-9 24083
16
Allopurinol Approved Phase 3 315-30-0 2094
17
Mannitol Approved, Investigational Phase 3 69-65-8 453 6251
18 tannic acid Approved, Nutraceutical Phase 3
19 Analgesics Phase 2, Phase 3
20 Anesthetics Phase 2, Phase 3
21 Anti-Arrhythmia Agents Phase 2, Phase 3
22 Anticonvulsants Phase 2, Phase 3
23 calcium channel blockers Phase 2, Phase 3
24 Calcium, Dietary Phase 2, Phase 3
25 Central Nervous System Depressants Phase 2, Phase 3,Phase 1
26 Peripheral Nervous System Agents Phase 2, Phase 3
27 Tocolytic Agents Phase 2, Phase 3
28 Hematinics Phase 3,Phase 1,Phase 2
29 Epoetin alfa Phase 3 113427-24-0
30 Antimetabolites Phase 3
31 Antirheumatic Agents Phase 3
32 diuretics Phase 3
33 Natriuretic Agents Phase 3
34
Menthol Approved Phase 2 2216-51-5 16666
35
Darbepoetin alfa Approved, Investigational Phase 1, Phase 2 11096-26-7, 209810-58-2
36 Antipruritics Phase 2
37 Dermatologic Agents Phase 2
38 Cerebrolysin Phase 2
39 Mitogens Phase 2
40 Neuroprotective Agents Phase 2
41 Nootropic Agents Phase 2
42 Anesthetics, General Phase 2
43 Anesthetics, Inhalation Phase 2
44 Xenon Phase 2
45
Ampicillin Approved, Vet_approved 69-53-4 6249
46
Fosphenytoin Approved 93390-81-9 56339
47
Midazolam Approved, Illicit 59467-70-8 4192
48
Phenobarbital Approved 50-06-6 4763
49 Anti-Bacterial Agents
50 Anti-Infective Agents

Interventional clinical trials:

(show all 41)

id Name Status NCT ID Phase Drugs
1 Efficacy of Yinzhihuang Oral Liquid on Indirect Bilirubin of Neonates With Glucose-6-phosphate Dehydrogenase Deficiency Unknown status NCT02594904 Phase 4 Yinzhihuang Oral Liquid
2 Use of a New Phototherapy Device (BBloo®) for the Treatment of Hyperbilirubinemia in the Newborn Infant Unknown status NCT02156050 Phase 4
3 Single High Dose Vitamin C, E in Severe Birth Asphyxia Completed NCT01743742 Phase 4 Vitamin E, Vitamin C
4 Supreme-LMA for Neonatal Resuscitation: a Prospective, Randomized Single-center Study Unknown status NCT01963936 Phase 3
5 Safety and Efficacy of Hypothermia to Treat Neonatal Hypoxic-Ischemic Encephalopathy Completed NCT00890409 Phase 3
6 Late Hypothermia for Hypoxic-Ischemic Encephalopathy Completed NCT00614744 Phase 2, Phase 3
7 Whole-Body Cooling for Birth Asphyxia in Term Infants Completed NCT00005772 Phase 3
8 Hypothermia Enhanced by Magnesium Sulphate Completed NCT02499393 Phase 2, Phase 3 Magnesium Sulfate
9 Preemie Hypothermia for Neonatal Encephalopathy Recruiting NCT01793129 Phase 2, Phase 3
10 PAEAN - Erythropoietin for Hypoxic Ischaemic Encephalopathy in Newborns Recruiting NCT03079167 Phase 3 Epoetin Alfa;Normal saline
11 High-dose Erythropoietin for Asphyxia and Encephalopathy Recruiting NCT02811263 Phase 3 Normal saline placebo;Erythropoietin
12 Efficacy of Erythropoietin to Improve Survival and Neurological Outcome in Hypoxic Ischemic Encephalopathy Active, not recruiting NCT01732146 Phase 3 erythropoietin Beta;Placebo
13 Erythropoietin in Management of Neonatal Hypoxic Ischemic Encephalopathy Not yet recruiting NCT03163589 Phase 3 Erythropoietin;normal saline
14 Effect of Allopurinol for Hypoxic-ischemic Brain Injury on Neurocognitive Outcome Not yet recruiting NCT03162653 Phase 3 Allopurinol;Mannitol
15 Optimizing (Longer, Deeper) Cooling for Neonatal Hypoxic-Ischemic Encephalopathy(HIE) Terminated NCT01192776 Phase 3
16 Moderate Hypothermia in Neonatal Hypoxic Ischemic Encephalopathy Completed NCT02826941 Phase 2
17 Darbe Administration in Newborns Undergoing Cooling for Encephalopathy Completed NCT01471015 Phase 1, Phase 2 Darbepoetin alfa;Darbepoetin alfa;Placebo
18 Study of Cerebrolysin for Treatment of Infants With History of Neonatal Hypoxic Ischemic Encephalopathy Completed NCT01059461 Phase 2 Cerebrolysin®
19 A Multi-site Study of Autologous Cord Blood Cells for Hypoxic Ischemic Encephalopathy Recruiting NCT02612155 Phase 2
20 Xenon and Cooling Therapy in Babies at High Risk of Brain Injury Following Poor Condition at Birth Recruiting NCT02071394 Phase 2 Xenon gas
21 Autologous Cord Blood and Human Placental Derived Stem Cells in Neonates With Severe Hypoxic-Ischemic Encephalopathy Not yet recruiting NCT02434965 Phase 2 HPDSC;Cord blood
22 Cord Blood for Neonatal Hypoxic-ischemic Encephalopathy Completed NCT00593242 Phase 1
23 Autologous Cord Blood Cell Therapy for Neonatal Encephalopathy Recruiting NCT02256618 Phase 1
24 Hypoxic-Ischemic Encephalopathy Therapy Optimization in Neonates for Better Neuroprotection With Inhalative CO2 Recruiting NCT02700854 Phase 1
25 Melatonin Treatment for Newborn Infants With Moderate to Severe Hypoxic Ischemic Encephalopathy Withdrawn NCT01904786 Phase 1 Melatonin;placebo
26 Pharmacokinetics of Ampicillin in Neonates With Moderate to Severe Hypoxic-Ischemic Encephalopathy Completed NCT03129620
27 The Impact of Electroencephalographic (EEG) Seizure Treatment in Neonatal Encephalopathy Completed NCT01027715
28 CoolCap Trial, Treatment of Perinatal Hypoxic-Ischemic Encephalopathy Completed NCT00383305
29 Determining Prevalence of Acute Bilirubin Encephalopathy in Developing Countries Completed NCT01754688
30 TOBY (TOtal Body hYpothermia): a Study of Treatment for Perinatal Asphyxia Completed NCT00147030
31 California Transport Cooling Trial Completed NCT01683383
32 Neonatal Neurologic Intensive Care Network of China Recruiting NCT02544100
33 Uterine Activity in Moderate-Severe Neonatal Encephalopathy: A Case Control Study Recruiting NCT03122808
34 Magnetic Resonance Biomarkers in Neonatal Encephalopathy Recruiting NCT01309711
35 Long Term Prognostic of Neonatal Hypoxic Ischemic Encephalopathy With Hypothermia Treatment Recruiting NCT02676063
36 Hypothermia for Encephalopathy in Low and Middle-Income Countries Trial Recruiting NCT02387385
37 Hyperbaric Oxygen Therapy Improves Outcome of Hypoxic-Ischemic Encephalopathy Recruiting NCT02894866
38 Neural Progenitor Cell and Paracrine Factors to Treat Hypoxic Ischemic Encephalopathy Recruiting NCT02854579
39 Umbilical Cord Milking for Neonates With Hypoxic Ischemic Encephalopathy Recruiting NCT02287077
40 Heart Beat Variability in Neonatal Encephalopathy Not yet recruiting NCT03179553
41 Role of Umbilical Cord Milking in the Management of Hypoxic-ischemic Encephalopathy in Neonates Not yet recruiting NCT03123081

Search NIH Clinical Center for Encephalopathy, Neonatal Severe

Genetic Tests for Encephalopathy, Neonatal Severe

Genetic tests related to Encephalopathy, Neonatal Severe:

id Genetic test Affiliating Genes
1 Severe Neonatal-Onset Encephalopathy with Microcephaly 29

Anatomical Context for Encephalopathy, Neonatal Severe

MalaCards organs/tissues related to Encephalopathy, Neonatal Severe:

39
Brain, Heart

Publications for Encephalopathy, Neonatal Severe

Variations for Encephalopathy, Neonatal Severe

ClinVar genetic disease variations for Encephalopathy, Neonatal Severe:

6 (show all 11)
id Gene Variation Type Significance SNP ID Assembly Location
1 MECP2 NM_004992.3(MECP2): c.473C> T (p.Thr158Met) single nucleotide variant Pathogenic/Likely pathogenic rs28934906 GRCh37 Chromosome X, 153296806: 153296806
2 MECP2 MECP2, 1-BP DEL, 806G deletion Pathogenic
3 MECP2 NM_004992.3(MECP2): c.808C> T (p.Arg270Ter) single nucleotide variant Pathogenic rs61750240 GRCh37 Chromosome X, 153296471: 153296471
4 MECP2 MECP2, 2-BP DEL, 488GG deletion Pathogenic
5 MECP2 MECP2, 32-BP DEL, NT1154 deletion Pathogenic
6 MECP2 NM_004992.3(MECP2): c.806delG (p.Gly269Alafs) deletion Pathogenic rs61750241 GRCh37 Chromosome X, 153296473: 153296473
7 MECP2 NM_004992.3(MECP2): c.119_120delAG (p.Glu40Glyfs) deletion Pathogenic rs267608428 GRCh38 Chromosome X, 154032464: 154032465
8 MECP2 NM_004992.3(MECP2): c.488_489delGG (p.Gly163Glufs) deletion Pathogenic rs267608488 GRCh37 Chromosome X, 153296790: 153296791
9 MECP2 NM_004992.3(MECP2): c.753dupC (p.Gly252Argfs) duplication Pathogenic rs61749751 GRCh37 Chromosome X, 153296526: 153296526
10 MECP2 NM_004992.3(MECP2): c.808delC (p.Arg270Glufs) deletion Pathogenic rs62931162 GRCh37 Chromosome X, 153296471: 153296471
11 MECP2 NM_001110792.1(MECP2): c.414-3_419delCAGTCCCCA deletion Pathogenic rs267608466 GRCh38 Chromosome X, 154031445: 154031453

Expression for Encephalopathy, Neonatal Severe

Search GEO for disease gene expression data for Encephalopathy, Neonatal Severe.

Pathways for Encephalopathy, Neonatal Severe

GO Terms for Encephalopathy, Neonatal Severe

Sources for Encephalopathy, Neonatal Severe

3 CDC
7 CNVD
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10 dbSNP
11 DGIdb
16 ExPASy
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30 HGMD
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33 ICD10
34 ICD10 via Orphanet
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43 MESH via Orphanet
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55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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