LISX2
MCID: LSS037
MIFTS: 32

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 73
Hydranencephaly with Abnormal Genitalia 57 13 6
Lissencephaly, X-Linked 2 57 75
Lisx2 57 75
Xlisg 57 75
Xlag 57 75
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 75
X-Linked Lissencephaly with Abnormal Genitalia 59
Chromosome Xq26.3 Duplication Syndrome 73
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:



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 thick skin and snoring. An important gene associated with Lissencephaly, X-Linked, 2 is ARX (Aristaless Related Homeobox). Affiliated tissues include brain, skin and testes, and related phenotypes are agenesis of corpus callosum and seizures

UniProtKB/Swiss-Prot : 75 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

Diseases in the Lissencephaly, X-Linked, 1 family:

Lissencephaly, X-Linked, 2

Diseases related to Lissencephaly, X-Linked, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 12)
# Related Disease Score Top Affiliating Genes
1 x-linked lissencephaly with abnormal genitalia 11.5
2 lissencephaly 11.4
3 chromosome xq26.3 duplication syndrome 11.4
4 corpus callosum, agenesis of, with abnormal genitalia 11.0
5 mental retardation, x-linked, with or without seizures, arx-related 11.0
6 epileptic encephalopathy, early infantile, 1 11.0
7 partington x-linked mental retardation syndrome 11.0
8 lissencephaly, x-linked, 1 10.2
9 diarrhea 10.2
10 epilepsy 10.0
11 hypogonadism 10.0
12 hypogonadotropism 10.0

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

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
high-arched palate
thin upper lip

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

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 death in infancy 59 Frequent (79-30%)
21 patent ductus arteriosus 59 Occasional (29-5%)
22 severe global developmental delay 32 HP:0011344
23 cryptorchidism 59 Very frequent (99-80%)
24 hypohidrosis 59 Frequent (79-30%)
25 specific learning disability 32 HP:0001328
26 exocrine pancreatic insufficiency 59 Occasional (29-5%)
27 prominent nasal bridge 32 HP:0000426
28 aganglionic megacolon 59 Occasional (29-5%)
29 decreased testicular size 32 HP:0008734
30 ventricular septal defect 59 Occasional (29-5%)
31 thin upper lip vermilion 32 HP:0000219
32 diarrhea 32 HP:0002014
33 hypoplasia of penis 59 Very frequent (99-80%)
34 high forehead 32 HP:0000348
35 wide anterior fontanel 32 HP:0000260
36 micropenis 32 HP:0000054
37 generalized hypotonia 32 HP:0001290
38 gliosis 32 HP:0002171
39 profound global developmental delay 32 HP:0012736
40 long upper lip 32 HP:0011341
41 duane anomaly 32 HP:0009921

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


thick skin, snoring

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

Anatomical Context for Lissencephaly, X-Linked, 2

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

41
Brain, Skin, Testes, Cortex

Publications for Lissencephaly, X-Linked, 2

Articles related to Lissencephaly, X-Linked, 2:

# Title Authors Year
1
A Neonate with X-linked Lissencephaly with Ambiguous Genitalia. ( 28553390 )
2017
2
Association between X-linked lissencephaly with ambiguous genitalia syndrome and lenticulostriate vasculopathy in neonate. ( 18412232 )
2008
3
Inactivation of Arx, the murine ortholog of the X-linked lissencephaly with ambiguous genitalia gene, leads to severe disorganization of the ventral telencephalon with impaired neuronal migration and differentiation. ( 17460091 )
2007
4
X-linked lissencephaly with ambiguous genitalia: delineation of further case. ( 10982975 )
2000

Variations for Lissencephaly, X-Linked, 2

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

75
# 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

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

6 (show top 50) (show all 62)
# Gene Variation Type Significance SNP ID Assembly Location
1 ARX NM_139058.2(ARX): c.1105G> T (p.Glu369Ter) single nucleotide variant Pathogenic rs104894746 GRCh37 Chromosome X, 25028391: 25028391
2 ARX NM_139058.2(ARX): c.1105G> T (p.Glu369Ter) single nucleotide variant Pathogenic rs104894746 GRCh38 Chromosome X, 25010274: 25010274
3 ARX NM_139058.2(ARX): c.232G> T (p.Glu78Ter) single nucleotide variant Pathogenic rs267606666 GRCh37 Chromosome X, 25031880: 25031880
4 ARX NM_139058.2(ARX): c.232G> T (p.Glu78Ter) single nucleotide variant Pathogenic rs267606666 GRCh38 Chromosome X, 25013763: 25013763
5 ARX NM_139058.2(ARX) duplication Pathogenic rs398124511 GRCh37 Chromosome X, 25031648: 25031671
6 ARX NM_139058.2(ARX) duplication Pathogenic rs398124511 GRCh38 Chromosome X, 25013531: 25013554
7 ARX NM_139058.2(ARX): c.1121T> A (p.Val374Asp) single nucleotide variant Likely pathogenic rs587783183 GRCh37 Chromosome X, 25025555: 25025555
8 ARX NM_139058.2(ARX): c.1121T> A (p.Val374Asp) single nucleotide variant Likely pathogenic rs587783183 GRCh38 Chromosome X, 25007438: 25007438
9 ARX NM_139058.2(ARX): c.1134C> A (p.Asn378Lys) single nucleotide variant Likely pathogenic rs587783184 GRCh37 Chromosome X, 25025542: 25025542
10 ARX NM_139058.2(ARX): c.1134C> A (p.Asn378Lys) single nucleotide variant Likely pathogenic rs587783184 GRCh38 Chromosome X, 25007425: 25007425
11 ARX NM_139058.2(ARX): c.1372delG (p.Ala458Argfs) deletion Pathogenic rs587783187 GRCh37 Chromosome X, 25025304: 25025304
12 ARX NM_139058.2(ARX): c.1372delG (p.Ala458Argfs) deletion Pathogenic rs587783187 GRCh38 Chromosome X, 25007187: 25007187
13 ARX NM_139058.2(ARX): c.1414C> T (p.Arg472Ter) single nucleotide variant Pathogenic rs587783189 GRCh37 Chromosome X, 25025262: 25025262
14 ARX NM_139058.2(ARX): c.1414C> T (p.Arg472Ter) single nucleotide variant Pathogenic rs587783189 GRCh38 Chromosome X, 25007145: 25007145
15 ARX NM_139058.2(ARX): c.1465delG (p.Ala489Profs) deletion Pathogenic rs587783191 GRCh37 Chromosome X, 25023011: 25023011
16 ARX NM_139058.2(ARX): c.1465delG (p.Ala489Profs) deletion Pathogenic rs587783191 GRCh38 Chromosome X, 25004894: 25004894
17 ARX NM_139058.2(ARX): c.335_368del34 (p.Ala112Glyfs) deletion Pathogenic rs587783199 GRCh37 Chromosome X, 25031744: 25031777
18 ARX NM_139058.2(ARX): c.335_368del34 (p.Ala112Glyfs) deletion Pathogenic rs587783199 GRCh38 Chromosome X, 25013627: 25013660
19 ARX NM_139058.2(ARX): c.1471dupC (p.Leu491Profs) duplication Pathogenic rs797045292 GRCh37 Chromosome X, 25023005: 25023005
20 ARX NM_139058.2(ARX): c.1471dupC (p.Leu491Profs) duplication Pathogenic rs797045292 GRCh38 Chromosome X, 25004888: 25004888
21 ARX NM_139058.2(ARX): c.1449-82_1469dup duplication Pathogenic GRCh37 Chromosome X, 25023007: 25023109
22 ARX NM_139058.2(ARX): c.1449-82_1469dup duplication Pathogenic GRCh38 Chromosome X, 25004890: 25004992
23 ARX NM_139058.2(ARX): c.1337dupC (p.Pro447Alafs) duplication Pathogenic rs797045291 GRCh38 Chromosome X, 25007222: 25007222
24 ARX NM_139058.2(ARX): c.1337dupC (p.Pro447Alafs) duplication Pathogenic rs797045291 GRCh37 Chromosome X, 25025339: 25025339
25 ARX NM_139058.2(ARX): c.1164_1165insCAAAG (p.Ala389Glnfs) insertion Pathogenic rs797045290 GRCh37 Chromosome X, 25025511: 25025512
26 ARX NM_139058.2(ARX): c.1164_1165insCAAAG (p.Ala389Glnfs) insertion Pathogenic rs797045290 GRCh38 Chromosome X, 25007394: 25007395
27 ARX NM_139058.2(ARX): c.1096delG (p.Asp366Thrfs) deletion Pathogenic rs797045289 GRCh37 Chromosome X, 25028400: 25028400
28 ARX NM_139058.2(ARX): c.1096delG (p.Asp366Thrfs) deletion Pathogenic rs797045289 GRCh38 Chromosome X, 25010283: 25010283
29 ARX NM_139058.2(ARX): c.562_563delGCinsTA (p.Ala188Ter) indel Pathogenic rs797045303 GRCh37 Chromosome X, 25031549: 25031550
30 ARX NM_139058.2(ARX): c.562_563delGCinsTA (p.Ala188Ter) indel Pathogenic rs797045303 GRCh38 Chromosome X, 25013432: 25013433
31 ARX NM_139058.2(ARX) duplication Likely pathogenic rs587776869 GRCh37 Chromosome X, 25031651: 25031686
32 ARX NM_139058.2(ARX) duplication Likely pathogenic rs587776869 GRCh38 Chromosome X, 25013534: 25013569
33 ARX NM_139058.2(ARX): c.409_410insG (p.Glu137Glyfs) duplication Pathogenic rs797045298 GRCh37 Chromosome X, 25031703: 25031703
34 ARX NM_139058.2(ARX): c.409_410insG (p.Glu137Glyfs) duplication Pathogenic rs797045298 GRCh38 Chromosome X, 25013586: 25013586
35 ARX NM_139058.2(ARX) duplication Pathogenic rs587783198 GRCh37 Chromosome X, 25031777: 25031800
36 ARX NM_139058.2(ARX) duplication Pathogenic rs587783198 GRCh38 Chromosome X, 25013660: 25013683
37 ARX NM_139058.2(ARX): c.304_305ins21 (p.?) insertion Pathogenic rs797045296 GRCh38 Chromosome X, 25013690: 25013691
38 ARX NM_139058.2(ARX): c.304_305ins21 (p.?) insertion Pathogenic rs797045296 GRCh37 Chromosome X, 25031807: 25031808
39 ARX NM_139058.2(ARX): c.1120-82_1469dup duplication Pathogenic
40 ARX NM_139058.2(ARX): c.790delC (p.Arg264Glyfs) deletion Pathogenic rs886043552 GRCh37 Chromosome X, 25031322: 25031322
41 ARX NM_139058.2(ARX): c.790delC (p.Arg264Glyfs) deletion Pathogenic rs886043552 GRCh38 Chromosome X, 25013205: 25013205
42 ARX NM_139058.2(ARX): c.614_642del29 (p.Leu205Profs) deletion Pathogenic rs886043728 GRCh37 Chromosome X, 25031470: 25031498
43 ARX NM_139058.2(ARX): c.614_642del29 (p.Leu205Profs) deletion Pathogenic rs886043728 GRCh38 Chromosome X, 25013353: 25013381
44 ARX NM_139058.2(ARX): c.1535_1549delTGGCATCGGGCGCCCinsGGCGCAG (p.Val512Glyfs) indel Pathogenic GRCh38 Chromosome X, 25004810: 25004824
45 ARX NM_139058.2(ARX): c.1535_1549delTGGCATCGGGCGCCCinsGGCGCAG (p.Val512Glyfs) indel Pathogenic GRCh37 Chromosome X, 25022927: 25022941
46 ARX NM_139058.2(ARX): c.1141delG (p.Ala381Profs) deletion Pathogenic GRCh37 Chromosome X, 25025535: 25025535
47 ARX NM_139058.2(ARX): c.1141delG (p.Ala381Profs) deletion Pathogenic GRCh38 Chromosome X, 25007418: 25007418
48 ARX NM_139058.2(ARX): c.995G> T (p.Arg332Leu) single nucleotide variant Pathogenic rs111033612 GRCh38 Chromosome X, 25013000: 25013000
49 ARX NM_139058.2(ARX): c.995G> T (p.Arg332Leu) single nucleotide variant Pathogenic rs111033612 GRCh37 Chromosome X, 25031117: 25031117
50 ARX NM_139058.2(ARX): c.617delG (p.Gly206Alafs) deletion Pathogenic rs587783202 GRCh38 Chromosome X, 25013378: 25013378

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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