LISX2
MCID: LSS037
MIFTS: 35

Lissencephaly, X-Linked, 2 (LISX2)

Categories: Endocrine diseases, Fetal diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Lissencephaly, X-Linked, 2

MalaCards integrated aliases for Lissencephaly, X-Linked, 2:

Name: Lissencephaly, X-Linked, 2 57 72
Hydranencephaly with Abnormal Genitalia 57 29 13 6
Lissencephaly, X-Linked 2 57 74
Lissencephaly 2, X-Linked 29 6
Lisx2 57 74
Xlisg 57 74
Xlag 57 74
X-Linked Lissencephaly-Corpus Callosum Agenesis-Genital Anomalies Syndrome 59
Lissencephaly, X-Linked, with Ambiguous Genitalia; Xlag 57
Lissencephaly, X-Linked, with Ambiguous Genitalia 57
X-Linked Lissencephaly with Ambiguous Genitalia 59
Lissencephaly X-Linked with Ambiguous Genitalia 74
X-Linked Lissencephaly with Abnormal Genitalia 59
Chromosome Xq26.3 Duplication Syndrome 72
Lissencephaly, X-Linked, Type 2 40
Xlag Syndrome 59

Characteristics:

Orphanet epidemiological data:

59
x-linked lissencephaly with abnormal genitalia
Inheritance: X-linked recessive; Age of onset: Neonatal; Age of death: early childhood;

OMIM:

57
Inheritance:
x-linked

Miscellaneous:
early death in males
some female carriers are more mildly affected


HPO:

32
lissencephaly, x-linked, 2:
Inheritance x-linked inheritance


Classifications:



External Ids:

MeSH 44 D054082
ICD10 via Orphanet 34 Q04.3
UMLS via Orphanet 73 C1846171
Orphanet 59 ORPHA452
UMLS 72 C1846171 C3891556

Summaries for Lissencephaly, X-Linked, 2

OMIM : 57 X-linked lissencephaly-2 (LISX2) is a developmental disorder characterized by structural brain anomalies, early-onset intractable seizures, severe psychomotor retardation, and ambiguous genitalia. Males are severely affected and often die within the first days or months of life, whereas females may be unaffected or have a milder phenotype (Bonneau et al., 2002). LISX2 is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from hydranencephaly and lissencephaly to Proud syndrome (300004) to infantile spasms without brain malformations (EIEE1; 308350) to syndromic (309510) and nonsyndromic (300419) mental retardation (Kato et al., 2004; Wallerstein et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432). (300215)

MalaCards based summary : Lissencephaly, X-Linked, 2, also known as hydranencephaly with abnormal genitalia, is related to x-linked lissencephaly with abnormal genitalia and lissencephaly, and has symptoms including snoring and thick skin. An important gene associated with Lissencephaly, X-Linked, 2 is ARX (Aristaless Related Homeobox). Affiliated tissues include brain, testes and skin, and related phenotypes are agenesis of corpus callosum and seizures

UniProtKB/Swiss-Prot : 74 Lissencephaly, X-linked 2: A classic type lissencephaly associated with abnormal genitalia. Patients have severe congenital or postnatal microcephaly, lissencephaly, agenesis of the corpus callosum, neonatal-onset intractable epilepsy, poor temperature regulation, chronic diarrhea, and ambiguous or underdeveloped genitalia.

Related Diseases for Lissencephaly, X-Linked, 2

Graphical network of the top 20 diseases related to Lissencephaly, X-Linked, 2:



Diseases related to Lissencephaly, X-Linked, 2

Symptoms & Phenotypes for Lissencephaly, X-Linked, 2

Human phenotypes related to Lissencephaly, X-Linked, 2:

59 32 (show all 41)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 agenesis of corpus callosum 59 32 Very frequent (99-80%) HP:0001274
2 seizures 59 32 Very frequent (99-80%) HP:0001250
3 muscular hypotonia 59 32 Frequent (79-30%) HP:0001252
4 spasticity 59 32 Occasional (29-5%) HP:0001257
5 micrognathia 59 32 Occasional (29-5%) HP:0000347
6 ventriculomegaly 59 32 Frequent (79-30%) HP:0002119
7 ambiguous genitalia 59 32 Very frequent (99-80%) HP:0000062
8 pachygyria 59 32 Very frequent (99-80%) HP:0001302
9 low-set ears 32 HP:0000369
10 high palate 32 HP:0000218
11 intellectual disability 59 Very frequent (99-80%)
12 hyperreflexia 32 HP:0001347
13 global developmental delay 59 Very frequent (99-80%)
14 wide nasal bridge 32 HP:0000431
15 malabsorption 59 Frequent (79-30%)
16 microcephaly 59 Very frequent (99-80%)
17 feeding difficulties in infancy 32 HP:0008872
18 prominent forehead 59 Occasional (29-5%)
19 long philtrum 32 HP:0000343
20 generalized hypotonia 32 HP:0001290
21 death in infancy 59 Frequent (79-30%)
22 patent ductus arteriosus 59 Occasional (29-5%)
23 severe global developmental delay 32 HP:0011344
24 cryptorchidism 59 Very frequent (99-80%)
25 hypohidrosis 59 Frequent (79-30%)
26 specific learning disability 32 HP:0001328
27 exocrine pancreatic insufficiency 59 Occasional (29-5%)
28 prominent nasal bridge 32 HP:0000426
29 aganglionic megacolon 59 Occasional (29-5%)
30 decreased testicular size 32 HP:0008734
31 micropenis 32 HP:0000054
32 ventricular septal defect 59 Occasional (29-5%)
33 thin upper lip vermilion 32 HP:0000219
34 diarrhea 32 HP:0002014
35 hypoplasia of penis 59 Very frequent (99-80%)
36 high forehead 32 HP:0000348
37 wide anterior fontanel 32 HP:0000260
38 profound global developmental delay 32 HP:0012736
39 gliosis 32 HP:0002171
40 long upper lip 32 HP:0011341
41 duane anomaly 32 HP:0009921

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Ears:
low-set ears

Head And Neck Nose:
wide nasal bridge
prominent nasal root
pinched nasal alae

Head And Neck Head:
high forehead
large anterior fontanelle

Head And Neck Mouth:
long upper lip
thin upper lip
high-arched palate

Endocrine Features:
hypothalamic dysfunction
impaired temperature regulation

Neurologic Central Nervous System:
hyperreflexia
hypotonia
enlarged ventricles
agenesis of the corpus callosum
psychomotor retardation, profound
more
Head And Neck Face:
long philtrum
micrognathia

Genitourinary External Genitalia Male:
ambiguous genitalia
small penis
small testes
underdeveloped scrotal folds

Abdomen Gastrointestinal:
poor feeding
diarrhea, chronic

Head And Neck Eyes:
thin optic nerves
duane anomaly (reported in 1 female)

Clinical features from OMIM:

300215

UMLS symptoms related to Lissencephaly, X-Linked, 2:


snoring, thick skin

Drugs & Therapeutics for Lissencephaly, X-Linked, 2

Search Clinical Trials , NIH Clinical Center for Lissencephaly, X-Linked, 2

Genetic Tests for Lissencephaly, X-Linked, 2

Genetic tests related to Lissencephaly, X-Linked, 2:

# Genetic test Affiliating Genes
1 Lissencephaly 2, X-Linked 29 ARX
2 Hydranencephaly with Abnormal Genitalia 29

Anatomical Context for Lissencephaly, X-Linked, 2

MalaCards organs/tissues related to Lissencephaly, X-Linked, 2:

41
Brain, Testes, Skin, Cortex

Publications for Lissencephaly, X-Linked, 2

Articles related to Lissencephaly, X-Linked, 2:

# Title Authors PMID Year
1
Mutations of ARX are associated with striking pleiotropy and consistent genotype-phenotype correlation. 38 8 71
14722918 2004
2
Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans. 8 71
12379852 2002
3
X-linked lissencephaly with absent corpus callosum and ambiguous genitalia (XLAG): clinical, magnetic resonance imaging, and neuropathological findings. 8 71
11891829 2002
4
Distinct DNA binding and transcriptional repression characteristics related to different ARX mutations. 71
22252899 2012
5
Targeted loss of Arx results in a developmental epilepsy mouse model and recapitulates the human phenotype in heterozygous females. 8
19439424 2009
6
Expansion of the ARX spectrum. 8
18462864 2008
7
ARX mutations in X-linked lissencephaly with abnormal genitalia. 71
12874405 2003
8
X-linked lissencephaly with ambiguous genitalia: delineation of further case. 8
10982975 2000
9
X-linked lissencephaly with absent corpus callosum and ambiguous genitalia. 8
10494089 1999
10
New X-linked syndrome with seizures, acquired micrencephaly, and agenesis of the corpus callosum. 8
1605226 1992

Variations for Lissencephaly, X-Linked, 2

ClinVar genetic disease variations for Lissencephaly, X-Linked, 2:

6 (show all 34)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 ARX NM_139058.3(ARX): c.1535_1549delinsGGCGCAG (p.Val512fs) indel Pathogenic rs1556046720 X:25022927-25022941 X:25004810-25004824
2 ARX NM_139058.3(ARX): c.1141del (p.Ala381fs) deletion Pathogenic rs1556049694 X:25025535-25025535 X:25007418-25007418
3 ARX NM_139058.3(ARX): c.306_308GGC[17] (p.Ala109_Ala115dup) short repeat Pathogenic rs387906492 X:25031779-25031781 X:25013662-25013664
4 ARX ARX, EX1-2DEL deletion Pathogenic
5 ARX NM_139058.3(ARX): c.1028T> A (p.Leu343Gln) single nucleotide variant Pathogenic rs104894741 X:25031084-25031084 X:25012967-25012967
6 ARX ARX, 32-BP DEL, NT420 deletion Pathogenic
7 ARX NM_139058.3(ARX): c.995G> A (p.Arg332His) single nucleotide variant Pathogenic rs111033612 X:25031117-25031117 X:25013000-25013000
8 ARX NM_139058.3(ARX): c.1117C> T (p.Gln373Ter) single nucleotide variant Pathogenic rs104894740 X:25028379-25028379 X:25010262-25010262
9 ARX NM_139058.3(ARX): c.1187dup (p.Gly397fs) duplication Pathogenic X:25025489-25025489 X:25007372-25007372
10 ARX NM_139058.3(ARX): c.1105G> T (p.Glu369Ter) single nucleotide variant Pathogenic rs104894746 X:25028391-25028391 X:25010274-25010274
11 ARX NM_139058.3(ARX): c.232G> T (p.Glu78Ter) single nucleotide variant Pathogenic rs267606666 X:25031880-25031880 X:25013763-25013763
12 ARX NM_139058.3(ARX): c.441_464dup (p.Ala148_Ala155dup) duplication Pathogenic rs398124510 X:25031648-25031671 X:25013531-25013554
13 ARX NM_139058.3(ARX): c.1372del (p.Ala458fs) deletion Pathogenic rs587783187 X:25025304-25025304 X:25007187-25007187
14 ARX NM_139058.3(ARX): c.1414C> T (p.Arg472Ter) single nucleotide variant Pathogenic rs587783189 X:25025262-25025262 X:25007145-25007145
15 ARX NM_139058.3(ARX): c.1465del (p.Ala489fs) deletion Pathogenic rs587783191 X:25023011-25023011 X:25004894-25004894
16 ARX NM_139058.3(ARX): c.335_368del (p.Ala112fs) deletion Pathogenic rs587783199 X:25031744-25031777 X:25013627-25013660
17 ARX NM_139058.3(ARX): c.617del (p.Gly206fs) deletion Pathogenic rs587783202 X:25031495-25031495 X:25013378-25013378
18 ARX NM_139058.3(ARX): c.995G> T (p.Arg332Leu) single nucleotide variant Pathogenic rs111033612 X:25031117-25031117 X:25013000-25013000
19 ARX NM_139058.3(ARX): c.1471dup (p.Leu491fs) duplication Pathogenic rs797045292 X:25023005-25023005 X:25004888-25004888
20 ARX NM_139058.3(ARX): c.1449-82_1469dup duplication Pathogenic rs1556046904 X:25023007-25023109 X:25004890-25004992
21 ARX NM_139058.3(ARX): c.1337dup (p.Pro447fs) duplication Pathogenic rs797045291 X:25025339-25025339 X:25007222-25007222
22 ARX NM_139058.3(ARX): c.1164_1165insCAAAG (p.Ala389fs) insertion Pathogenic rs797045290 X:25025511-25025512 X:25007394-25007395
23 ARX NM_139058.3(ARX): c.1096del (p.Asp366fs) deletion Pathogenic rs797045289 X:25028400-25028400 X:25010283-25010283
24 ARX NM_139058.3(ARX): c.562_563delinsTA (p.Ala188Ter) indel Pathogenic rs797045303 X:25031549-25031550 X:25013432-25013433
25 ARX NM_139058.3(ARX): c.409dup (p.Glu137fs) duplication Pathogenic rs797045298 X:25031703-25031703 X:25013586-25013586
26 ARX NM_139058.3(ARX): c.306_308GGC[18] (p.Ala108_Ala115dup) short repeat Pathogenic rs387906492 X:25031777-25031800 X:25013660-25013683
27 ARX NM_139058.2(ARX): c.304_305ins21 (p.?) insertion Pathogenic X:25031807-25031808 X:25013690-25013691
28 ARX NM_139058.2(ARX): c.1120-82_1469dup duplication Pathogenic
29 ARX NM_139058.3(ARX): c.790del (p.Arg264fs) deletion Pathogenic rs886043552 X:25031322-25031322 X:25013205-25013205
30 ARX NM_139058.3(ARX): c.426_461dup (p.Gly143_Ala154dup) duplication Likely pathogenic rs1556056131 X:25031651-25031686 X:25013534-25013569
31 ARX NM_139058.3(ARX): c.1121T> A (p.Val374Asp) single nucleotide variant Likely pathogenic rs587783183 X:25025555-25025555 X:25007438-25007438
32 ARX NM_139058.3(ARX): c.1134C> A (p.Asn378Lys) single nucleotide variant Likely pathogenic rs587783184 X:25025542-25025542 X:25007425-25007425
33 ARX NM_139058.3(ARX): c.1170C> T (p.Gly390=) single nucleotide variant Conflicting interpretations of pathogenicity rs761632870 X:25025506-25025506 X:25007389-25007389
34 ARX NM_139058.3(ARX): c.187G> A (p.Ala63Thr) single nucleotide variant Uncertain significance X:25033668-25033668 X:25015551-25015551

UniProtKB/Swiss-Prot genetic disease variations for Lissencephaly, X-Linked, 2:

74
# Symbol AA change Variation ID SNP ID
1 ARX p.Arg332His VAR_015178 rs111033612
2 ARX p.Leu343Gln VAR_015179 rs104894741
3 ARX p.Arg332Pro VAR_033260
4 ARX p.Pro353Arg VAR_033262
5 ARX p.Ala521Thr VAR_033263 rs746120093

Expression for Lissencephaly, X-Linked, 2

Search GEO for disease gene expression data for Lissencephaly, X-Linked, 2.

Pathways for Lissencephaly, X-Linked, 2

GO Terms for Lissencephaly, X-Linked, 2

Sources for Lissencephaly, X-Linked, 2

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7 CNVD
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
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73 UMLS via Orphanet
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