MCSZ
MCID: MCR064
MIFTS: 24

Microcephaly, Seizures, and Developmental Delay (MCSZ)

Categories: Genetic diseases, Neuronal 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 25 75 73
Epileptic Encephalopathy, Early Infantile, 10 57 53 25 13
Eiee10 57 53 25 75
Mcsz 57 53 25 75
Early Infantile Epileptic Encephalopathy 10 75 29 6
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

Genetics Home Reference : 25 Microcephaly, seizures, and developmental delay (MCSZ) is a condition characterized by an abnormally small head size (microcephaly) and neurological problems related to impaired brain development before birth. Affected individuals typically have recurrent seizures (epilepsy) beginning in infancy and delayed development of motor skills, such as sitting and walking. Speech is also delayed, and some affected individuals are never able to speak. Intellectual disability and behavior problems, primarily hyperactivity, are also common features of MCSZ. Rarely, individuals with MCSZ also have poor balance and coordination (ataxia).

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 brain and skeletal muscle, and related phenotypes are seizures and ataxia

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)

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 10.0

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 motor delay 32 HP:0001270
7 hyporeflexia 32 occasional (7.5%) HP:0001265
8 generalized hypotonia 32 HP:0001290
9 hypoplasia of the corpus callosum 32 HP:0002079
10 hyperactivity 32 HP:0000752
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
Brain, 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 top 50) (show all 74)
# 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.1127-8C> T single nucleotide variant Conflicting interpretations of pathogenicity rs3739203 GRCh37 Chromosome 19, 50365370: 50365370
8 PNKP NM_007254.3(PNKP): c.1127-8C> T single nucleotide variant Conflicting interpretations of pathogenicity rs3739203 GRCh38 Chromosome 19, 49862113: 49862113
9 PNKP NM_007254.3(PNKP): c.1189-10delG deletion Benign/Likely benign rs3739205 GRCh37 Chromosome 19, 50365148: 50365148
10 PNKP NM_007254.3(PNKP): c.1189-10delG deletion Benign/Likely benign rs3739205 GRCh38 Chromosome 19, 49861891: 49861891
11 PNKP NM_007254.3(PNKP): c.1385G> A (p.Arg462Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs376854895 GRCh37 Chromosome 19, 50364866: 50364866
12 PNKP NM_007254.3(PNKP): c.1385G> A (p.Arg462Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs376854895 GRCh38 Chromosome 19, 49861609: 49861609
13 PNKP NM_007254.3(PNKP): c.1497G> A (p.Leu499=) single nucleotide variant Conflicting interpretations of pathogenicity rs142199280 GRCh37 Chromosome 19, 50364574: 50364574
14 PNKP NM_007254.3(PNKP): c.1497G> A (p.Leu499=) single nucleotide variant Conflicting interpretations of pathogenicity rs142199280 GRCh38 Chromosome 19, 49861317: 49861317
15 PNKP NM_007254.3(PNKP): c.538C> A (p.Arg180Ser) single nucleotide variant Benign/Likely benign rs3739185 GRCh37 Chromosome 19, 50367621: 50367621
16 PNKP NM_007254.3(PNKP): c.538C> A (p.Arg180Ser) single nucleotide variant Benign/Likely benign rs3739185 GRCh38 Chromosome 19, 49864364: 49864364
17 PNKP NM_007254.3(PNKP): c.58C> T (p.Pro20Ser) single nucleotide variant Benign/Likely benign rs3739168 GRCh37 Chromosome 19, 50370404: 50370404
18 PNKP NM_007254.3(PNKP): c.58C> T (p.Pro20Ser) single nucleotide variant Benign/Likely benign rs3739168 GRCh38 Chromosome 19, 49867147: 49867147
19 PNKP NM_007254.3(PNKP): c.901C> T (p.Arg301Trp) single nucleotide variant Uncertain significance rs201503405 GRCh37 Chromosome 19, 50365830: 50365830
20 PNKP NM_007254.3(PNKP): c.901C> T (p.Arg301Trp) single nucleotide variant Uncertain significance rs201503405 GRCh38 Chromosome 19, 49862573: 49862573
21 PNKP NM_007254.3(PNKP): c.672C> T (p.Arg224=) single nucleotide variant Conflicting interpretations of pathogenicity rs151180981 GRCh38 Chromosome 19, 49864036: 49864036
22 PNKP NM_007254.3(PNKP): c.672C> T (p.Arg224=) single nucleotide variant Conflicting interpretations of pathogenicity rs151180981 GRCh37 Chromosome 19, 50367293: 50367293
23 PNKP NM_007254.3(PNKP): c.783G> A (p.Pro261=) single nucleotide variant Benign/Likely benign rs145307985 GRCh38 Chromosome 19, 49863722: 49863722
24 PNKP NM_007254.3(PNKP): c.783G> A (p.Pro261=) single nucleotide variant Benign/Likely benign rs145307985 GRCh37 Chromosome 19, 50366979: 50366979
25 PNKP NM_007254.3(PNKP): c.876A> G (p.Gly292=) single nucleotide variant Conflicting interpretations of pathogenicity rs3739199 GRCh38 Chromosome 19, 49862598: 49862598
26 PNKP NM_007254.3(PNKP): c.876A> G (p.Gly292=) single nucleotide variant Conflicting interpretations of pathogenicity rs3739199 GRCh37 Chromosome 19, 50365855: 50365855
27 PNKP NM_007254.3(PNKP): c.939T> C (p.Phe313=) single nucleotide variant Conflicting interpretations of pathogenicity rs149731642 GRCh38 Chromosome 19, 49862461: 49862461
28 PNKP NM_007254.3(PNKP): c.939T> C (p.Phe313=) single nucleotide variant Conflicting interpretations of pathogenicity rs149731642 GRCh37 Chromosome 19, 50365718: 50365718
29 PNKP NM_007254.3(PNKP): c.1126+9C> T single nucleotide variant Conflicting interpretations of pathogenicity rs3739202 GRCh38 Chromosome 19, 49862176: 49862176
30 PNKP NM_007254.3(PNKP): c.1126+9C> T single nucleotide variant Conflicting interpretations of pathogenicity rs3739202 GRCh37 Chromosome 19, 50365433: 50365433
31 PNKP NM_007254.3(PNKP): c.1522G> A (p.Glu508Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs146478958 GRCh38 Chromosome 19, 49861292: 49861292
32 PNKP NM_007254.3(PNKP): c.1522G> A (p.Glu508Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs146478958 GRCh37 Chromosome 19, 50364549: 50364549
33 PNKP NM_007254.3(PNKP): c.*15C> T single nucleotide variant Conflicting interpretations of pathogenicity rs1050332 GRCh38 Chromosome 19, 49861233: 49861233
34 PNKP NM_007254.3(PNKP): c.*15C> T single nucleotide variant Conflicting interpretations of pathogenicity rs1050332 GRCh37 Chromosome 19, 50364490: 50364490
35 PNKP NM_007254.3(PNKP): c.1482C> A (p.Gly494=) single nucleotide variant Uncertain significance rs60279874 GRCh37 Chromosome 19, 50364589: 50364589
36 PNKP NM_007254.3(PNKP): c.1482C> A (p.Gly494=) single nucleotide variant Uncertain significance rs60279874 GRCh38 Chromosome 19, 49861332: 49861332
37 PNKP NM_007254.3(PNKP): c.1319C> G (p.Ala440Gly) single nucleotide variant Uncertain significance rs377688490 GRCh37 Chromosome 19, 50364932: 50364932
38 PNKP NM_007254.3(PNKP): c.1319C> G (p.Ala440Gly) single nucleotide variant Uncertain significance rs377688490 GRCh38 Chromosome 19, 49861675: 49861675
39 PNKP NM_007254.3(PNKP): c.1295_1298+6delCCAGGTAGCG deletion Pathogenic/Likely pathogenic rs587784366 GRCh37 Chromosome 19, 50365023: 50365032
40 PNKP NM_007254.3(PNKP): c.1295_1298+6delCCAGGTAGCG deletion Pathogenic/Likely pathogenic rs587784366 GRCh38 Chromosome 19, 49861766: 49861775
41 PNKP NM_007254.3(PNKP): c.994C> T (p.Pro332Ser) single nucleotide variant Uncertain significance rs373922574 GRCh37 Chromosome 19, 50365663: 50365663
42 PNKP NM_007254.3(PNKP): c.994C> T (p.Pro332Ser) single nucleotide variant Uncertain significance rs373922574 GRCh38 Chromosome 19, 49862406: 49862406
43 PNKP NM_007254.3(PNKP): c.968C> T (p.Thr323Met) single nucleotide variant Conflicting interpretations of pathogenicity rs372148913 GRCh37 Chromosome 19, 50365689: 50365689
44 PNKP NM_007254.3(PNKP): c.968C> T (p.Thr323Met) single nucleotide variant Conflicting interpretations of pathogenicity rs372148913 GRCh38 Chromosome 19, 49862432: 49862432
45 PNKP NM_007254.3(PNKP): c.861G> C (p.Val287=) single nucleotide variant Uncertain significance rs75203375 GRCh37 Chromosome 19, 50365951: 50365951
46 PNKP NM_007254.3(PNKP): c.861G> C (p.Val287=) single nucleotide variant Uncertain significance rs75203375 GRCh38 Chromosome 19, 49862694: 49862694
47 PNKP NM_007254.3(PNKP): c.744+8T> C single nucleotide variant Uncertain significance rs587784370 GRCh37 Chromosome 19, 50367213: 50367213
48 PNKP NM_007254.3(PNKP): c.744+8T> C single nucleotide variant Uncertain significance rs587784370 GRCh38 Chromosome 19, 49863956: 49863956
49 PNKP NM_007254.3(PNKP): c.671G> A (p.Arg224His) single nucleotide variant Uncertain significance rs199705876 GRCh37 Chromosome 19, 50367294: 50367294
50 PNKP NM_007254.3(PNKP): c.671G> A (p.Arg224His) single nucleotide variant Uncertain significance rs199705876 GRCh38 Chromosome 19, 49864037: 49864037

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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