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 56 71
Hydranencephaly with Abnormal Genitalia 56 29 13 6
Lissencephaly, X-Linked 2 56 73
Lissencephaly 2, X-Linked 29 6
Lisx2 56 73
Xlisg 56 73
Xlag 56 73
X-Linked Lissencephaly-Corpus Callosum Agenesis-Genital Anomalies Syndrome 58
Lissencephaly, X-Linked, with Ambiguous Genitalia; Xlag 56
Lissencephaly, X-Linked, with Ambiguous Genitalia 56
X-Linked Lissencephaly with Ambiguous Genitalia 58
Lissencephaly X-Linked with Ambiguous Genitalia 73
X-Linked Lissencephaly with Abnormal Genitalia 58
Chromosome Xq26.3 Duplication Syndrome 71
Lissencephaly, X-Linked, Type 2 39
Xlag Syndrome 58

Characteristics:

Orphanet epidemiological data:

58
x-linked lissencephaly with abnormal genitalia
Inheritance: X-linked recessive; Age of onset: Neonatal; Age of death: early childhood;

OMIM:

56
Inheritance:
x-linked

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


HPO:

31
lissencephaly, x-linked, 2:
Inheritance x-linked inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


External Ids:

OMIM 56 300215
OMIM Phenotypic Series 56 PS607432
MeSH 43 D054082
ICD10 via Orphanet 33 Q04.3
UMLS via Orphanet 72 C1846171
Orphanet 58 ORPHA452
UMLS 71 C1846171 C3891556

Summaries for Lissencephaly, X-Linked, 2

OMIM : 56 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 cortex, and related phenotypes are muscular hypotonia and spasticity

UniProtKB/Swiss-Prot : 73 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:

58 31 (show all 42)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 muscular hypotonia 58 31 Frequent (79-30%) HP:0001252
2 spasticity 58 31 Occasional (29-5%) HP:0001257
3 micrognathia 58 31 Occasional (29-5%) HP:0000347
4 ventriculomegaly 58 31 Frequent (79-30%) HP:0002119
5 agenesis of corpus callosum 58 31 Very frequent (99-80%) HP:0001274
6 ambiguous genitalia 58 31 Very frequent (99-80%) HP:0000062
7 pachygyria 58 31 Very frequent (99-80%) HP:0001302
8 intellectual disability 58 Very frequent (99-80%)
9 global developmental delay 58 Very frequent (99-80%)
10 wide nasal bridge 31 HP:0000431
11 seizures 58 Very frequent (99-80%)
12 malabsorption 58 Frequent (79-30%)
13 microcephaly 58 Very frequent (99-80%)
14 feeding difficulties in infancy 31 HP:0008872
15 prominent forehead 58 Occasional (29-5%)
16 hyperreflexia 31 HP:0001347
17 cryptorchidism 58 Very frequent (99-80%)
18 hypohidrosis 58 Frequent (79-30%)
19 high palate 31 HP:0000218
20 low-set ears 31 HP:0000369
21 specific learning disability 31 HP:0001328
22 exocrine pancreatic insufficiency 58 Occasional (29-5%)
23 aganglionic megacolon 58 Occasional (29-5%)
24 micropenis 31 HP:0000054
25 patent ductus arteriosus 58 Occasional (29-5%)
26 thin upper lip vermilion 31 HP:0000219
27 long philtrum 31 HP:0000343
28 death in infancy 58 Frequent (79-30%)
29 prominent nasal bridge 31 HP:0000426
30 ventricular septal defect 58 Occasional (29-5%)
31 high forehead 31 HP:0000348
32 hypoplasia of penis 58 Very frequent (99-80%)
33 severe global developmental delay 31 HP:0011344
34 decreased testicular size 31 HP:0008734
35 wide anterior fontanel 31 HP:0000260
36 profound global developmental delay 31 HP:0012736
37 diarrhea 31 HP:0002014
38 generalized hypotonia 31 HP:0001290
39 duane anomaly 31 HP:0009921
40 long upper lip 31 HP:0011341
41 gliosis 31 HP:0002171
42 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Nose:
wide nasal bridge
prominent nasal root
pinched nasal alae

Head And Neck Face:
micrognathia
long philtrum

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 Ears:
low-set ears

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:

40
Brain, Testes, Cortex, Skin

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. 61 6 56
14722918 2004
2
Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans. 6 56
12379852 2002
3
X-linked lissencephaly with absent corpus callosum and ambiguous genitalia (XLAG): clinical, magnetic resonance imaging, and neuropathological findings. 56 6
11891829 2002
4
Distinct DNA binding and transcriptional repression characteristics related to different ARX mutations. 6
22252899 2012
5
Targeted loss of Arx results in a developmental epilepsy mouse model and recapitulates the human phenotype in heterozygous females. 56
19439424 2009
6
Expansion of the ARX spectrum. 56
18462864 2008
7
ARX mutations in X-linked lissencephaly with abnormal genitalia. 6
12874405 2003
8
X-linked lissencephaly with ambiguous genitalia: delineation of further case. 56
10982975 2000
9
X-linked lissencephaly with absent corpus callosum and ambiguous genitalia. 56
10494089 1999
10
New X-linked syndrome with seizures, acquired micrencephaly, and agenesis of the corpus callosum. 56
1605226 1992

Variations for Lissencephaly, X-Linked, 2

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

6 (show all 35) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ARX NM_139058.3(ARX):c.525C>G (p.Tyr175Ter)SNV Pathogenic 689380 X:25031587-25031587 X:25013470-25013470
2 ARX NM_139058.3(ARX):c.306_308GGC[17] (p.Ala109_Ala115dup)short repeat Pathogenic 11186 rs387906492 X:25031776-25031777 X:25013659-25013660
3 ARX ARX, 32-BP DEL, NT420deletion Pathogenic 11190
4 ARX NM_139058.3(ARX):c.995G>A (p.Arg332His)SNV Pathogenic 11192 rs111033612 X:25031117-25031117 X:25013000-25013000
5 ARX NM_139058.3(ARX):c.1117C>T (p.Gln373Ter)SNV Pathogenic 11193 rs104894740 X:25028379-25028379 X:25010262-25010262
6 ARX NM_139058.3(ARX):c.1187dup (p.Gly397fs)duplication Pathogenic 11194 rs1328291159 X:25025488-25025489 X:25007371-25007372
7 ARX ARX, EX1-2DELdeletion Pathogenic 11195
8 ARX NM_139058.3(ARX):c.1028T>A (p.Leu343Gln)SNV Pathogenic 11197 rs104894741 X:25031084-25031084 X:25012967-25012967
9 ARX NM_139058.3(ARX):c.1105G>T (p.Glu369Ter)SNV Pathogenic 11201 rs104894746 X:25028391-25028391 X:25010274-25010274
10 ARX NM_139058.3(ARX):c.232G>T (p.Glu78Ter)SNV Pathogenic 11205 rs267606666 X:25031880-25031880 X:25013763-25013763
11 ARX NM_139058.3(ARX):c.441_464dup (p.Ala148_Ala155dup)duplication Pathogenic 96455 rs398124510 X:25031647-25031648 X:25013530-25013531
12 ARX NM_139058.3(ARX):c.1372del (p.Ala458fs)deletion Pathogenic 157744 rs587783187 X:25025304-25025304 X:25007187-25007187
13 ARX NM_139058.3(ARX):c.1414C>T (p.Arg472Ter)SNV Pathogenic 157746 rs587783189 X:25025262-25025262 X:25007145-25007145
14 ARX NM_139058.3(ARX):c.1465del (p.Ala489fs)deletion Pathogenic 157748 rs587783191 X:25023011-25023011 X:25004894-25004894
15 ARX NM_139058.3(ARX):c.335_368del (p.Ala112fs)deletion Pathogenic 157756 rs587783199 X:25031744-25031777 X:25013627-25013660
16 ARX NM_139058.3(ARX):c.617del (p.Gly206fs)deletion Pathogenic 157759 rs587783202 X:25031495-25031495 X:25013378-25013378
17 ARX NM_139058.3(ARX):c.995G>T (p.Arg332Leu)SNV Pathogenic 157765 rs111033612 X:25031117-25031117 X:25013000-25013000
18 ARX NM_139058.3(ARX):c.1337dup (p.Pro447fs)duplication Pathogenic 210319 rs797045291 X:25025338-25025339 X:25007221-25007222
19 ARX NM_139058.3(ARX):c.1164_1165insCAAAG (p.Ala389fs)insertion Pathogenic 210318 rs797045290 X:25025511-25025512 X:25007394-25007395
20 ARX NM_139058.3(ARX):c.1471dup (p.Leu491fs)duplication Pathogenic 210321 rs797045292 X:25023004-25023005 X:25004887-25004888
21 ARX NM_139058.3(ARX):c.1449-82_1469dupduplication Pathogenic 210320 rs1556046904 X:25023006-25023007 X:25004889-25004890
22 ARX NM_139058.3(ARX):c.1096del (p.Asp366fs)deletion Pathogenic 210316 rs797045289 X:25028400-25028400 X:25010283-25010283
23 ARX NM_139058.3(ARX):c.562_563delinsTA (p.Ala188Ter)indel Pathogenic 210335 rs797045303 X:25031549-25031550 X:25013432-25013433
24 ARX NM_139058.3(ARX):c.409dup (p.Glu137fs)duplication Pathogenic 210330 rs797045298 X:25031702-25031703 X:25013585-25013586
25 ARX NM_139058.3(ARX):c.306_308GGC[18] (p.Ala108_Ala115dup)short repeat Pathogenic 210327 rs387906492 X:25031776-25031777 X:25013659-25013660
26 ARX NM_139058.2(ARX):c.304_305ins21 (p.?)insertion Pathogenic 210326 X:25031807-25031808 X:25013690-25013691
27 ARX NM_139058.2(ARX):c.1120-82_1469dupduplication Pathogenic 210317
28 ARX NM_139058.3(ARX):c.1535_1549delinsGGCGCAG (p.Val512fs)indel Pathogenic 434399 rs1556046720 X:25022927-25022941 X:25004810-25004824
29 ARX NM_139058.3(ARX):c.1141del (p.Ala381fs)deletion Pathogenic 434396 rs1556049694 X:25025535-25025535 X:25007418-25007418
30 ARX NM_139058.3(ARX):c.790del (p.Arg264fs)deletion Pathogenic 287023 rs886043552 X:25031322-25031322 X:25013205-25013205
31 ARX NM_139058.3(ARX):c.426_461dup (p.Gly143_Ala154dup)duplication Likely pathogenic 210331 rs1556056131 X:25031650-25031651 X:25013533-25013534
32 ARX NM_139058.3(ARX):c.1121T>A (p.Val374Asp)SNV Likely pathogenic 157740 rs587783183 X:25025555-25025555 X:25007438-25007438
33 ARX NM_139058.3(ARX):c.1134C>A (p.Asn378Lys)SNV Likely pathogenic 157741 rs587783184 X:25025542-25025542 X:25007425-25007425
34 ARX NM_139058.3(ARX):c.1170C>T (p.Gly390=)SNV Conflicting interpretations of pathogenicity 234531 rs761632870 X:25025506-25025506 X:25007389-25007389
35 ARX NM_139058.3(ARX):c.187G>A (p.Ala63Thr)SNV Uncertain significance 581240 rs769996976 X:25033668-25033668 X:25015551-25015551

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

73
# 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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
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50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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