MCID: MCR064
MIFTS: 22

Microcephaly, Seizures, and Developmental Delay

Categories: Genetic diseases, Rare diseases

Aliases & Classifications for Microcephaly, Seizures, and Developmental Delay

MalaCards integrated aliases for Microcephaly, Seizures, and Developmental Delay:

Name: Microcephaly, Seizures, and Developmental Delay 57 53 75 73
Epileptic Encephalopathy, Early Infantile, 10 57 53 13
Early Infantile Epileptic Encephalopathy 10 75 29 6
Eiee10 57 53 75
Mcsz 57 53 75
Epileptic Encephalopathy, Early Infantile, 10; Eiee10 57
Encephalopathy, Epileptic, Early Infantile, Type 10 40
Microcephaly - Seizures - Developmental Delay 53
Early Infantile Epileptic Encephalopathy-10 53

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset prenatally or at birth
some patients may have a more protracted disorder with neurodegeneration


HPO:

32
microcephaly, seizures, and developmental delay:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Microcephaly, Seizures, and Developmental Delay

OMIM : 57 Microcephaly, seizures, and developmental delay is an autosomal recessive neurodevelopmental disorder with onset in infancy. There is a range of phenotypic severity: some patients have a disease course consistent with early infantile epileptic encephalopathy (EIEE), whereas others have more well-controlled seizures and a protracted course associated with cerebellar atrophy and peripheral neuropathy (Shen et al., 2010 and Poulton et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350). (613402)

MalaCards based summary : Microcephaly, Seizures, and Developmental Delay, also known as epileptic encephalopathy, early infantile, 10, is related to microcephaly. An important gene associated with Microcephaly, Seizures, and Developmental Delay is PNKP (Polynucleotide Kinase 3'-Phosphatase). Affiliated tissues include skeletal muscle, and related phenotypes are seizures and ataxia

UniProtKB/Swiss-Prot : 75 Microcephaly, seizures, and developmental delay: A disease characterized by infantile-onset seizures, microcephaly, severe intellectual disability and delayed motor milestones with absent speech or only achieving a few words. Most patients also have behavioral problems with hyperactivity. Microcephaly is progressive and without neuronal migration or structural abnormalities, consistent with primary microcephaly.

Related Diseases for Microcephaly, Seizures, and Developmental Delay

Diseases related to Microcephaly, Seizures, and Developmental Delay via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 microcephaly 9.9

Symptoms & Phenotypes for Microcephaly, Seizures, and Developmental Delay

Symptoms via clinical synopsis from OMIM:

57
Neurologic Behavioral Psychiatric Manifestations:
hyperactivity

Neurologic Central Nervous System:
enlarged ventricles
delayed motor development
mental retardation, severe
cerebellar ataxia (in some patients)
simplified gyral pattern
more
Head And Neck Head:
microcephaly, progressive

Muscle Soft Tissue:
hypotonia
muscular atrophy

Neurologic Peripheral Nervous System:
hyporeflexia (in some patients)
sensorimotor polyneuropathy (in some patients)

Laboratory Abnormalities:
patient cells show defective dna repair in response to irradiation and free radical damage


Clinical features from OMIM:

613402

Human phenotypes related to Microcephaly, Seizures, and Developmental Delay:

32 (show all 13)
# Description HPO Frequency HPO Source Accession
1 seizures 32 HP:0001250
2 ataxia 32 occasional (7.5%) HP:0001251
3 intellectual disability, severe 32 HP:0010864
4 skeletal muscle atrophy 32 HP:0003202
5 ventriculomegaly 32 HP:0002119
6 hyporeflexia 32 occasional (7.5%) HP:0001265
7 motor delay 32 HP:0001270
8 hypoplasia of the corpus callosum 32 HP:0002079
9 hyperactivity 32 HP:0000752
10 generalized hypotonia 32 HP:0001290
11 epileptic encephalopathy 32 HP:0200134
12 progressive microcephaly 32 HP:0000253
13 cortical gyral simplification 32 HP:0009879

Drugs & Therapeutics for Microcephaly, Seizures, and Developmental Delay

Search Clinical Trials , NIH Clinical Center for Microcephaly, Seizures, and Developmental Delay

Genetic Tests for Microcephaly, Seizures, and Developmental Delay

Genetic tests related to Microcephaly, Seizures, and Developmental Delay:

# Genetic test Affiliating Genes
1 Early Infantile Epileptic Encephalopathy 10 29 PNKP

Anatomical Context for Microcephaly, Seizures, and Developmental Delay

MalaCards organs/tissues related to Microcephaly, Seizures, and Developmental Delay:

41
Skeletal Muscle

Publications for Microcephaly, Seizures, and Developmental Delay

Articles related to Microcephaly, Seizures, and Developmental Delay:

# Title Authors Year
1
Impact of PNKP mutations associated with microcephaly, seizures and developmental delay on enzyme activity and DNA strand break repair. ( 22508754 )
2012

Variations for Microcephaly, Seizures, and Developmental Delay

UniProtKB/Swiss-Prot genetic disease variations for Microcephaly, Seizures, and Developmental Delay:

75
# Symbol AA change Variation ID SNP ID
1 PNKP p.Leu176Phe VAR_063835 rs267606957
2 PNKP p.Glu326Lys VAR_063836 rs267606956
3 PNKP p.Arg462Pro VAR_076537 rs376854895

ClinVar genetic disease variations for Microcephaly, Seizures, and Developmental Delay:

6
(show all 46)
# Gene Variation Type Significance SNP ID Assembly Location
1 PNKP NM_007254.3(PNKP): c.976G> A (p.Glu326Lys) single nucleotide variant Pathogenic rs267606956 GRCh37 Chromosome 19, 50365681: 50365681
2 PNKP NM_007254.3(PNKP): c.976G> A (p.Glu326Lys) single nucleotide variant Pathogenic rs267606956 GRCh38 Chromosome 19, 49862424: 49862424
3 PNKP NM_007254.3(PNKP): c.1253_1269dupGGGTCGCCATCGACAAC (p.Thr424Glyfs) duplication Pathogenic rs587784365 GRCh38 Chromosome 19, 49861801: 49861817
4 PNKP NM_007254.3(PNKP): c.1253_1269dupGGGTCGCCATCGACAAC (p.Thr424Glyfs) duplication Pathogenic rs587784365 GRCh37 Chromosome 19, 50365058: 50365074
5 PNKP NM_007254.3(PNKP): c.526C> T (p.Leu176Phe) single nucleotide variant Pathogenic rs267606957 GRCh37 Chromosome 19, 50367633: 50367633
6 PNKP NM_007254.3(PNKP): c.526C> T (p.Leu176Phe) single nucleotide variant Pathogenic rs267606957 GRCh38 Chromosome 19, 49864376: 49864376
7 PNKP NM_007254.3(PNKP): c.1482C> A (p.Gly494=) single nucleotide variant Uncertain significance rs60279874 GRCh37 Chromosome 19, 50364589: 50364589
8 PNKP NM_007254.3(PNKP): c.1482C> A (p.Gly494=) single nucleotide variant Uncertain significance rs60279874 GRCh38 Chromosome 19, 49861332: 49861332
9 PNKP NM_007254.3(PNKP): c.1319C> G (p.Ala440Gly) single nucleotide variant Uncertain significance rs377688490 GRCh37 Chromosome 19, 50364932: 50364932
10 PNKP NM_007254.3(PNKP): c.1319C> G (p.Ala440Gly) single nucleotide variant Uncertain significance rs377688490 GRCh38 Chromosome 19, 49861675: 49861675
11 PNKP NM_007254.3(PNKP): c.1295_1298+6delCCAGGTAGCG deletion Pathogenic/Likely pathogenic rs587784366 GRCh37 Chromosome 19, 50365023: 50365032
12 PNKP NM_007254.3(PNKP): c.1295_1298+6delCCAGGTAGCG deletion Pathogenic/Likely pathogenic rs587784366 GRCh38 Chromosome 19, 49861766: 49861775
13 PNKP NM_007254.3(PNKP): c.994C> T (p.Pro332Ser) single nucleotide variant Uncertain significance rs373922574 GRCh37 Chromosome 19, 50365663: 50365663
14 PNKP NM_007254.3(PNKP): c.994C> T (p.Pro332Ser) single nucleotide variant Uncertain significance rs373922574 GRCh38 Chromosome 19, 49862406: 49862406
15 PNKP NM_007254.3(PNKP): c.968C> T (p.Thr323Met) single nucleotide variant Conflicting interpretations of pathogenicity rs372148913 GRCh37 Chromosome 19, 50365689: 50365689
16 PNKP NM_007254.3(PNKP): c.968C> T (p.Thr323Met) single nucleotide variant Conflicting interpretations of pathogenicity rs372148913 GRCh38 Chromosome 19, 49862432: 49862432
17 PNKP NM_007254.3(PNKP): c.861G> C (p.Val287=) single nucleotide variant Uncertain significance rs75203375 GRCh37 Chromosome 19, 50365951: 50365951
18 PNKP NM_007254.3(PNKP): c.861G> C (p.Val287=) single nucleotide variant Uncertain significance rs75203375 GRCh38 Chromosome 19, 49862694: 49862694
19 PNKP NM_007254.3(PNKP): c.744+8T> C single nucleotide variant Uncertain significance rs587784370 GRCh37 Chromosome 19, 50367213: 50367213
20 PNKP NM_007254.3(PNKP): c.744+8T> C single nucleotide variant Uncertain significance rs587784370 GRCh38 Chromosome 19, 49863956: 49863956
21 PNKP NM_007254.3(PNKP): c.671G> A (p.Arg224His) single nucleotide variant Uncertain significance rs199705876 GRCh37 Chromosome 19, 50367294: 50367294
22 PNKP NM_007254.3(PNKP): c.671G> A (p.Arg224His) single nucleotide variant Uncertain significance rs199705876 GRCh38 Chromosome 19, 49864037: 49864037
23 PNKP NM_007254.3(PNKP): c.666C> T (p.Ile222=) single nucleotide variant Conflicting interpretations of pathogenicity rs587784369 GRCh37 Chromosome 19, 50367299: 50367299
24 PNKP NM_007254.3(PNKP): c.666C> T (p.Ile222=) single nucleotide variant Conflicting interpretations of pathogenicity rs587784369 GRCh38 Chromosome 19, 49864042: 49864042
25 PNKP NM_007254.3(PNKP): c.579-4G> A single nucleotide variant Conflicting interpretations of pathogenicity rs371834726 GRCh37 Chromosome 19, 50367497: 50367497
26 PNKP NM_007254.3(PNKP): c.579-4G> A single nucleotide variant Conflicting interpretations of pathogenicity rs371834726 GRCh38 Chromosome 19, 49864240: 49864240
27 PNKP NM_007254.3(PNKP): c.457T> C (p.Leu153=) single nucleotide variant Uncertain significance rs587784368 GRCh37 Chromosome 19, 50368425: 50368425
28 PNKP NM_007254.3(PNKP): c.457T> C (p.Leu153=) single nucleotide variant Uncertain significance rs587784368 GRCh38 Chromosome 19, 49865168: 49865168
29 PNKP NM_007254.3(PNKP): c.416G> A (p.Arg139His) single nucleotide variant Conflicting interpretations of pathogenicity rs34472250 GRCh37 Chromosome 19, 50368466: 50368466
30 PNKP NM_007254.3(PNKP): c.416G> A (p.Arg139His) single nucleotide variant Conflicting interpretations of pathogenicity rs34472250 GRCh38 Chromosome 19, 49865209: 49865209
31 PNKP NM_007254.3(PNKP): c.302C> T (p.Pro101Leu) single nucleotide variant Uncertain significance rs587784367 GRCh37 Chromosome 19, 50368580: 50368580
32 PNKP NM_007254.3(PNKP): c.302C> T (p.Pro101Leu) single nucleotide variant Uncertain significance rs587784367 GRCh38 Chromosome 19, 49865323: 49865323
33 PNKP NM_007254.3(PNKP): c.188C> T (p.Ala63Val) single nucleotide variant Conflicting interpretations of pathogenicity rs3739173 GRCh37 Chromosome 19, 50369666: 50369666
34 PNKP NM_007254.3(PNKP): c.188C> T (p.Ala63Val) single nucleotide variant Conflicting interpretations of pathogenicity rs3739173 GRCh38 Chromosome 19, 49866409: 49866409
35 PNKP NM_007254.3(PNKP): c.151+18T> G single nucleotide variant Conflicting interpretations of pathogenicity rs55756709 GRCh37 Chromosome 19, 50370293: 50370293
36 PNKP NM_007254.3(PNKP): c.151+18T> G single nucleotide variant Conflicting interpretations of pathogenicity rs55756709 GRCh38 Chromosome 19, 49867036: 49867036
37 PNKP NM_007254.3(PNKP): c.1221_1223delCAC (p.Thr408del) deletion Likely pathogenic rs786205207 GRCh38 Chromosome 19, 49861847: 49861849
38 PNKP NM_007254.3(PNKP): c.1221_1223delCAC (p.Thr408del) deletion Likely pathogenic rs786205207 GRCh37 Chromosome 19, 50365104: 50365106
39 PNKP NM_007254.3(PNKP): c.1317_1321dupAGCCG (p.Ala441Glufs) duplication Pathogenic rs796052862 GRCh38 Chromosome 19, 49861673: 49861677
40 PNKP NM_007254.3(PNKP): c.1317_1321dupAGCCG (p.Ala441Glufs) duplication Pathogenic rs796052862 GRCh37 Chromosome 19, 50364930: 50364934
41 PNKP NM_007254.3(PNKP): c.1029+2T> C single nucleotide variant Conflicting interpretations of pathogenicity rs199919568 GRCh38 Chromosome 19, 49862369: 49862369
42 PNKP NM_007254.3(PNKP): c.1029+2T> C single nucleotide variant Conflicting interpretations of pathogenicity rs199919568 GRCh37 Chromosome 19, 50365626: 50365626
43 PNKP NM_007254.3(PNKP): c.1387-49_1387-33del deletion Pathogenic rs752902474 GRCh37 Chromosome 19, 50364800: 50364816
44 PNKP NM_007254.3(PNKP): c.1387-49_1387-33del deletion Pathogenic rs752902474 GRCh38 Chromosome 19, 49861543: 49861559
45 PNKP NM_007254.3(PNKP): c.636+1G> T single nucleotide variant Pathogenic GRCh38 Chromosome 19, 49864178: 49864178
46 PNKP NM_007254.3(PNKP): c.636+1G> T single nucleotide variant Pathogenic GRCh37 Chromosome 19, 50367435: 50367435

Expression for Microcephaly, Seizures, and Developmental Delay

Search GEO for disease gene expression data for Microcephaly, Seizures, and Developmental Delay.

Pathways for Microcephaly, Seizures, and Developmental Delay

GO Terms for Microcephaly, Seizures, and Developmental Delay

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