MCID: LSS037
MIFTS: 30

Lissencephaly, X-Linked, 2

Categories: Genetic diseases, Neuronal diseases, Endocrine diseases, Fetal 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 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 ambiguous genitalia and micrognathia

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:

# Related Disease Score Top Affiliating Genes
1 x-linked lissencephaly with abnormal genitalia 11.4
2 lissencephaly 11.3
3 chromosome xq26.3 duplication syndrome 11.2

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

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

Anatomical Context for Lissencephaly, X-Linked, 2

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

41
Brain, Testes, Cortex, Skin

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 65)
# Gene Variation Type Significance SNP ID Assembly Location
1 ARX NM_139058.2(ARX) NT expansion Pathogenic rs387906492 GRCh37 Chromosome X, 25031779: 25031781
2 ARX NM_139058.2(ARX) NT expansion Pathogenic rs387906492 GRCh38 Chromosome X, 25013662: 25013664
3 ARX ARX, 32-BP DEL, NT420 deletion Pathogenic
4 ARX ARX, 1-BP DEL, 790C deletion Pathogenic
5 ARX NM_139058.2(ARX): c.995G> A (p.Arg332His) single nucleotide variant Pathogenic rs111033612 GRCh37 Chromosome X, 25031117: 25031117
6 ARX NM_139058.2(ARX): c.995G> A (p.Arg332His) single nucleotide variant Pathogenic rs111033612 GRCh38 Chromosome X, 25013000: 25013000
7 ARX NM_139058.2(ARX): c.1117C> T (p.Gln373Ter) single nucleotide variant Pathogenic rs104894740 GRCh37 Chromosome X, 25028379: 25028379
8 ARX NM_139058.2(ARX): c.1117C> T (p.Gln373Ter) single nucleotide variant Pathogenic rs104894740 GRCh38 Chromosome X, 25010262: 25010262
9 ARX ARX, 1-BP INS, 1188C insertion Pathogenic
10 ARX ARX, EX1-2DEL deletion Pathogenic
11 ARX ARX, 1-BP DEL, 1372G deletion Pathogenic
12 ARX NM_139058.2(ARX): c.1028T> A (p.Leu343Gln) single nucleotide variant Pathogenic rs104894741 GRCh37 Chromosome X, 25031084: 25031084
13 ARX NM_139058.2(ARX): c.1028T> A (p.Leu343Gln) single nucleotide variant Pathogenic rs104894741 GRCh38 Chromosome X, 25012967: 25012967
14 ARX NM_139058.2(ARX): c.1105G> T (p.Glu369Ter) single nucleotide variant Pathogenic rs104894746 GRCh37 Chromosome X, 25028391: 25028391
15 ARX NM_139058.2(ARX): c.1105G> T (p.Glu369Ter) single nucleotide variant Pathogenic rs104894746 GRCh38 Chromosome X, 25010274: 25010274
16 ARX ARX, 1-BP DEL, 617G deletion Pathogenic
17 ARX NM_139058.2(ARX): c.232G> T (p.Glu78Ter) single nucleotide variant Pathogenic rs267606666 GRCh37 Chromosome X, 25031880: 25031880
18 ARX NM_139058.2(ARX): c.232G> T (p.Glu78Ter) single nucleotide variant Pathogenic rs267606666 GRCh38 Chromosome X, 25013763: 25013763
19 ARX NM_139058.2(ARX) duplication Pathogenic rs398124511 GRCh37 Chromosome X, 25031648: 25031671
20 ARX NM_139058.2(ARX) duplication Pathogenic rs398124511 GRCh38 Chromosome X, 25013531: 25013554
21 ARX NM_139058.2(ARX): c.1465delG (p.Ala489Profs) deletion Pathogenic rs587783191 GRCh37 Chromosome X, 25023011: 25023011
22 ARX NM_139058.2(ARX): c.1465delG (p.Ala489Profs) deletion Pathogenic rs587783191 GRCh38 Chromosome X, 25004894: 25004894
23 ARX NM_139058.2(ARX): c.1121T> A (p.Val374Asp) single nucleotide variant Likely pathogenic rs587783183 GRCh37 Chromosome X, 25025555: 25025555
24 ARX NM_139058.2(ARX): c.1121T> A (p.Val374Asp) single nucleotide variant Likely pathogenic rs587783183 GRCh38 Chromosome X, 25007438: 25007438
25 ARX NM_139058.2(ARX): c.1134C> A (p.Asn378Lys) single nucleotide variant Likely pathogenic rs587783184 GRCh37 Chromosome X, 25025542: 25025542
26 ARX NM_139058.2(ARX): c.1134C> A (p.Asn378Lys) single nucleotide variant Likely pathogenic rs587783184 GRCh38 Chromosome X, 25007425: 25007425
27 ARX NM_139058.2(ARX): c.1372delG (p.Ala458Argfs) deletion Pathogenic rs587783187 GRCh37 Chromosome X, 25025304: 25025304
28 ARX NM_139058.2(ARX): c.1372delG (p.Ala458Argfs) deletion Pathogenic rs587783187 GRCh38 Chromosome X, 25007187: 25007187
29 ARX NM_139058.2(ARX): c.1414C> T (p.Arg472Ter) single nucleotide variant Pathogenic rs587783189 GRCh37 Chromosome X, 25025262: 25025262
30 ARX NM_139058.2(ARX): c.1414C> T (p.Arg472Ter) single nucleotide variant Pathogenic rs587783189 GRCh38 Chromosome X, 25007145: 25007145
31 ARX NM_139058.2(ARX): c.335_368del34 (p.Ala112Glyfs) deletion Pathogenic rs587783199 GRCh37 Chromosome X, 25031744: 25031777
32 ARX NM_139058.2(ARX): c.335_368del34 (p.Ala112Glyfs) deletion Pathogenic rs587783199 GRCh38 Chromosome X, 25013627: 25013660
33 ARX NM_139058.2(ARX): c.617delG (p.Gly206Alafs) deletion Pathogenic rs587783202 GRCh37 Chromosome X, 25031495: 25031495
34 ARX NM_139058.2(ARX): c.617delG (p.Gly206Alafs) deletion Pathogenic rs587783202 GRCh38 Chromosome X, 25013378: 25013378
35 ARX NM_139058.2(ARX): c.995G> T (p.Arg332Leu) single nucleotide variant Pathogenic rs111033612 GRCh37 Chromosome X, 25031117: 25031117
36 ARX NM_139058.2(ARX): c.995G> T (p.Arg332Leu) single nucleotide variant Pathogenic rs111033612 GRCh38 Chromosome X, 25013000: 25013000
37 ARX NM_139058.2(ARX): c.1471dupC (p.Leu491Profs) duplication Pathogenic rs797045292 GRCh37 Chromosome X, 25023005: 25023005
38 ARX NM_139058.2(ARX): c.1471dupC (p.Leu491Profs) duplication Pathogenic rs797045292 GRCh38 Chromosome X, 25004888: 25004888
39 ARX NM_139058.2(ARX): c.1449-82_1469dup duplication Pathogenic GRCh37 Chromosome X, 25023007: 25023109
40 ARX NM_139058.2(ARX): c.1449-82_1469dup duplication Pathogenic GRCh38 Chromosome X, 25004890: 25004992
41 ARX NM_139058.2(ARX): c.1337dupC (p.Pro447Alafs) duplication Pathogenic rs797045291 GRCh38 Chromosome X, 25007222: 25007222
42 ARX NM_139058.2(ARX): c.1337dupC (p.Pro447Alafs) duplication Pathogenic rs797045291 GRCh37 Chromosome X, 25025339: 25025339
43 ARX NM_139058.2(ARX): c.1164_1165insCAAAG (p.Ala389Glnfs) insertion Pathogenic rs797045290 GRCh37 Chromosome X, 25025511: 25025512
44 ARX NM_139058.2(ARX): c.1164_1165insCAAAG (p.Ala389Glnfs) insertion Pathogenic rs797045290 GRCh38 Chromosome X, 25007394: 25007395
45 ARX NM_139058.2(ARX): c.1096delG (p.Asp366Thrfs) deletion Pathogenic rs797045289 GRCh37 Chromosome X, 25028400: 25028400
46 ARX NM_139058.2(ARX): c.1096delG (p.Asp366Thrfs) deletion Pathogenic rs797045289 GRCh38 Chromosome X, 25010283: 25010283
47 ARX NM_139058.2(ARX): c.562_563delGCinsTA (p.Ala188Ter) indel Pathogenic rs797045303 GRCh37 Chromosome X, 25031549: 25031550
48 ARX NM_139058.2(ARX): c.562_563delGCinsTA (p.Ala188Ter) indel Pathogenic rs797045303 GRCh38 Chromosome X, 25013432: 25013433
49 ARX NM_139058.2(ARX) duplication Likely pathogenic rs587776869 GRCh37 Chromosome X, 25031651: 25031686
50 ARX NM_139058.2(ARX) duplication Likely pathogenic rs587776869 GRCh38 Chromosome X, 25013534: 25013569

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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69 SNOMED-CT via HPO
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71 TGDB
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74 UMLS via Orphanet
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