MCID: XLN107
MIFTS: 29

X-Linked Lissencephaly with Abnormal Genitalia

Categories: Rare diseases, Reproductive diseases

Aliases & Classifications for X-Linked Lissencephaly with Abnormal Genitalia

MalaCards integrated aliases for X-Linked Lissencephaly with Abnormal Genitalia:

Name: X-Linked Lissencephaly with Abnormal Genitalia 53 25
X-Linked Lissencephaly with Ambiguous Genitalia 53 25
Lissencephaly 2, X-Linked 29 6
Xlisg 53 25
X-Linked Lissencephaly-Agenesis of the Corpus Callosum-Genital Anomalies Syndrome 53
X-Linked Lissencephaly - Agenesis of the Corpus Callosum - Genital Anomalies 53
X-Linked Lissencephaly-Corpus Callosum Agenesis-Genital Anomalies Syndrome 53
Lissencephaly, X-Linked, with Ambiguous Genitalia 53
Hydranencephaly with Abnormal Genitalia 53
Chromosome Xq26.3 Duplication Syndrome 73
Lissencephaly, X-Linked, Type 2 ) 40
Lissencephaly, X-Linked, 2 73
Lissencephaly, X-Linked 2 53
X-Linked Lissencephaly 2 25
Xlag Syndrome 53
Xlag Syndrome 53
Lisx2 25
Xlag 25

Characteristics:

HPO:

32
x-linked lissencephaly with abnormal genitalia:
Mortality/Aging death in infancy


Classifications:



Summaries for X-Linked Lissencephaly with Abnormal Genitalia

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 452Disease definitionX-linked lissencephaly with abnormal genitalia (XLAG) is a severe neurological disorder that only manifests in genotypic males and includes lissencephaly with posterior-to-anterior gradient and only moderate increase in thickness of the cortex, absent corpus callosum, neonatal-onset severe epilepsy, hypothalamic dysfunction including defective temperature regulation, and ambiguous genitalia with micropenis and cryptorchidism. XLAG differs considerably from classical lissencephaly, as the resulting cortical thickness is only 6-7 mm in XLAG, rather than 15-20 mm seen in classical lissencephaly due to mutations of the PAFAH1B1 or DCX genes. In 2002, mutations in the X-linked aristaless-related homeobox gene (ARX; Xp21.3) were identified in individuals with XLAG and in some of their female relatives. Mouse Arx and human ARX are highly expressed in both dorsal and ventral telencephalon, including the neocortical ventricular zone and germinal zone of the ganglionic eminence, with less intense signals in the subventricular zone, cortical plate, hippocampus, basal ganglia and ventral thalamus. Arx-deficient mice showed deficient tangential migration and abnormal differentiation of GABAergic interneurons in the ganglionic eminence and neocortex, as well as abnormal testicular differentiation. These characteristics include some of the clinical features of XLAG in humans. The ARX mutations in XLAG patients were predominantly premature termination mutations (large deletions, frameshift, nonsense mutations, splice site mutations) while the missense mutations were less common and located essentially in the homeobox domain. Patients carrying nonconservative missense mutations within the homeobox, showed less severe XLAG, while conservative substitution in the homeodomain caused Proud syndrome (ACC with abnormal genitalia). A non conservative missense mutation near the C-terminal aristaless domain caused unusually severe XLAG with microcephaly and mild cerebellar hypoplasia. The ARX mutations are also associated with a spectrum of milder phenotypes, without macroscopic malformations of the brain, such as X-linked infantile spasms, a syndrome featuring mental retardation associated with distal dystonic movements (Partington syndrome; see this term), autistic features and nonsyndromicintellectual deficit.Visit the Orphanet disease page for more resources.

MalaCards based summary : X-Linked Lissencephaly with Abnormal Genitalia, also known as x-linked lissencephaly with ambiguous genitalia, is related to chromosome xq26.3 duplication syndrome and lissencephaly, x-linked, 2, and has symptoms including snoring and thick skin. An important gene associated with X-Linked Lissencephaly with Abnormal Genitalia is ARX (Aristaless Related Homeobox). Affiliated tissues include brain, cortex and thalamus, and related phenotypes are cryptorchidism and ambiguous genitalia

Genetics Home Reference : 25 X-linked lissencephaly with abnormal genitalia (XLAG) is a condition that affects the development of the brain and genitalia. It occurs most often in males.

Related Diseases for X-Linked Lissencephaly with Abnormal Genitalia

Diseases related to X-Linked Lissencephaly with Abnormal Genitalia via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 chromosome xq26.3 duplication syndrome 11.7
2 lissencephaly, x-linked, 2 11.4
3 lissencephaly, x-linked, 1 10.5
4 lissencephaly 10.5
5 diarrhea 10.1
6 epilepsy 10.1

Graphical network of the top 20 diseases related to X-Linked Lissencephaly with Abnormal Genitalia:



Diseases related to X-Linked Lissencephaly with Abnormal Genitalia

Symptoms & Phenotypes for X-Linked Lissencephaly with Abnormal Genitalia

Human phenotypes related to X-Linked Lissencephaly with Abnormal Genitalia:

32 (show all 20)
# Description HPO Frequency HPO Source Accession
1 cryptorchidism 32 hallmark (90%) HP:0000028
2 ambiguous genitalia 32 hallmark (90%) HP:0000062
3 microcephaly 32 hallmark (90%) HP:0000252
4 micrognathia 32 occasional (7.5%) HP:0000347
5 hypohidrosis 32 frequent (33%) HP:0000966
6 intellectual disability 32 hallmark (90%) HP:0001249
7 seizures 32 hallmark (90%) HP:0001250
8 muscular hypotonia 32 frequent (33%) HP:0001252
9 spasticity 32 occasional (7.5%) HP:0001257
10 global developmental delay 32 hallmark (90%) HP:0001263
11 agenesis of corpus callosum 32 hallmark (90%) HP:0001274
12 pachygyria 32 hallmark (90%) HP:0001302
13 ventricular septal defect 32 occasional (7.5%) HP:0001629
14 patent ductus arteriosus 32 occasional (7.5%) HP:0001643
15 exocrine pancreatic insufficiency 32 occasional (7.5%) HP:0001738
16 malabsorption 32 frequent (33%) HP:0002024
17 ventriculomegaly 32 frequent (33%) HP:0002119
18 aganglionic megacolon 32 occasional (7.5%) HP:0002251
19 hypoplasia of penis 32 hallmark (90%) HP:0008736
20 prominent forehead 32 occasional (7.5%) HP:0011220

UMLS symptoms related to X-Linked Lissencephaly with Abnormal Genitalia:


snoring, thick skin

Drugs & Therapeutics for X-Linked Lissencephaly with Abnormal Genitalia

Search Clinical Trials , NIH Clinical Center for X-Linked Lissencephaly with Abnormal Genitalia

Genetic Tests for X-Linked Lissencephaly with Abnormal Genitalia

Genetic tests related to X-Linked Lissencephaly with Abnormal Genitalia:

# Genetic test Affiliating Genes
1 Lissencephaly 2, X-Linked 29 ARX

Anatomical Context for X-Linked Lissencephaly with Abnormal Genitalia

MalaCards organs/tissues related to X-Linked Lissencephaly with Abnormal Genitalia:

41
Brain, Cortex, Thalamus, Skin, Hypothalamus, Testes

Publications for X-Linked Lissencephaly with Abnormal Genitalia

Articles related to X-Linked Lissencephaly with Abnormal Genitalia:

(show all 11)
# Title Authors Year
1
A Neonate with X-linked Lissencephaly with Ambiguous Genitalia. ( 28553390 )
2017
2
Watery diarrhea-hypopotassemia-acidosis syndrome like diarrhea in a case with X-linked lissencephaly with abnormal genitalia. ( 26129807 )
2015
3
Analysis of the hypothalamus in a case of X-linked lissencephaly with abnormal genitalia (XLAG). ( 18842366 )
2009
4
Aristaless-related homeobox gene disruption leads to abnormal distribution of GABAergic interneurons in human neocortex: evidence based on a case of X-linked lissencephaly with abnormal genitalia (XLAG). ( 18458920 )
2008
5
Association between X-linked lissencephaly with ambiguous genitalia syndrome and lenticulostriate vasculopathy in neonate. ( 18412232 )
2008
6
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
7
X-linked lissencephaly with abnormal genitalia as a tangential migration disorder causing intractable epilepsy: proposal for a new term, "interneuronopathy". ( 15921244 )
2005
8
X-linked lissencephaly with abnormal genitalia associated with renal phosphate wasting. ( 15248105 )
2004
9
ARX mutations in X-linked lissencephaly with abnormal genitalia. ( 12874405 )
2003
10
Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans. ( 12379852 )
2002
11
X-linked lissencephaly with ambiguous genitalia: delineation of further case. ( 10982975 )
2000

Variations for X-Linked Lissencephaly with Abnormal Genitalia

ClinVar genetic disease variations for X-Linked Lissencephaly with Abnormal Genitalia:

6
(show top 50) (show all 61)
# 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 ARX, 1-BP DEL, 617G deletion Pathogenic
15 ARX NM_139058.2(ARX): c.232G> T (p.Glu78Ter) single nucleotide variant Pathogenic rs267606666 GRCh37 Chromosome X, 25031880: 25031880
16 ARX NM_139058.2(ARX): c.232G> T (p.Glu78Ter) single nucleotide variant Pathogenic rs267606666 GRCh38 Chromosome X, 25013763: 25013763
17 ARX NM_139058.2(ARX) duplication Pathogenic rs398124511 GRCh37 Chromosome X, 25031648: 25031671
18 ARX NM_139058.2(ARX) duplication Pathogenic rs398124511 GRCh38 Chromosome X, 25013531: 25013554
19 ARX NM_139058.2(ARX): c.1465delG (p.Ala489Profs) deletion Pathogenic rs587783191 GRCh37 Chromosome X, 25023011: 25023011
20 ARX NM_139058.2(ARX): c.1465delG (p.Ala489Profs) deletion Pathogenic rs587783191 GRCh38 Chromosome X, 25004894: 25004894
21 ARX NM_139058.2(ARX): c.1121T> A (p.Val374Asp) single nucleotide variant Likely pathogenic rs587783183 GRCh37 Chromosome X, 25025555: 25025555
22 ARX NM_139058.2(ARX): c.1121T> A (p.Val374Asp) single nucleotide variant Likely pathogenic rs587783183 GRCh38 Chromosome X, 25007438: 25007438
23 ARX NM_139058.2(ARX): c.1134C> A (p.Asn378Lys) single nucleotide variant Likely pathogenic rs587783184 GRCh37 Chromosome X, 25025542: 25025542
24 ARX NM_139058.2(ARX): c.1134C> A (p.Asn378Lys) single nucleotide variant Likely pathogenic rs587783184 GRCh38 Chromosome X, 25007425: 25007425
25 ARX NM_139058.2(ARX): c.1372delG (p.Ala458Argfs) deletion Pathogenic rs587783187 GRCh37 Chromosome X, 25025304: 25025304
26 ARX NM_139058.2(ARX): c.1372delG (p.Ala458Argfs) deletion Pathogenic rs587783187 GRCh38 Chromosome X, 25007187: 25007187
27 ARX NM_139058.2(ARX): c.1414C> T (p.Arg472Ter) single nucleotide variant Pathogenic rs587783189 GRCh37 Chromosome X, 25025262: 25025262
28 ARX NM_139058.2(ARX): c.1414C> T (p.Arg472Ter) single nucleotide variant Pathogenic rs587783189 GRCh38 Chromosome X, 25007145: 25007145
29 ARX NM_139058.2(ARX): c.335_368del34 (p.Ala112Glyfs) deletion Pathogenic rs587783199 GRCh37 Chromosome X, 25031744: 25031777
30 ARX NM_139058.2(ARX): c.335_368del34 (p.Ala112Glyfs) deletion Pathogenic rs587783199 GRCh38 Chromosome X, 25013627: 25013660
31 ARX NM_139058.2(ARX): c.617delG (p.Gly206Alafs) deletion Pathogenic rs587783202 GRCh37 Chromosome X, 25031495: 25031495
32 ARX NM_139058.2(ARX): c.617delG (p.Gly206Alafs) deletion Pathogenic rs587783202 GRCh38 Chromosome X, 25013378: 25013378
33 ARX NM_139058.2(ARX): c.995G> T (p.Arg332Leu) single nucleotide variant Pathogenic rs111033612 GRCh37 Chromosome X, 25031117: 25031117
34 ARX NM_139058.2(ARX): c.995G> T (p.Arg332Leu) single nucleotide variant Pathogenic rs111033612 GRCh38 Chromosome X, 25013000: 25013000
35 ARX NM_139058.2(ARX): c.1471dupC (p.Leu491Profs) duplication Pathogenic rs797045292 GRCh37 Chromosome X, 25023005: 25023005
36 ARX NM_139058.2(ARX): c.1471dupC (p.Leu491Profs) duplication Pathogenic rs797045292 GRCh38 Chromosome X, 25004888: 25004888
37 ARX NM_139058.2(ARX): c.1449-82_1469dup duplication Pathogenic GRCh37 Chromosome X, 25023007: 25023109
38 ARX NM_139058.2(ARX): c.1449-82_1469dup duplication Pathogenic GRCh38 Chromosome X, 25004890: 25004992
39 ARX NM_139058.2(ARX): c.1337dupC (p.Pro447Alafs) duplication Pathogenic rs797045291 GRCh38 Chromosome X, 25007222: 25007222
40 ARX NM_139058.2(ARX): c.1337dupC (p.Pro447Alafs) duplication Pathogenic rs797045291 GRCh37 Chromosome X, 25025339: 25025339
41 ARX NM_139058.2(ARX): c.1164_1165insCAAAG (p.Ala389Glnfs) insertion Pathogenic rs797045290 GRCh37 Chromosome X, 25025511: 25025512
42 ARX NM_139058.2(ARX): c.1164_1165insCAAAG (p.Ala389Glnfs) insertion Pathogenic rs797045290 GRCh38 Chromosome X, 25007394: 25007395
43 ARX NM_139058.2(ARX): c.1096delG (p.Asp366Thrfs) deletion Pathogenic rs797045289 GRCh37 Chromosome X, 25028400: 25028400
44 ARX NM_139058.2(ARX): c.1096delG (p.Asp366Thrfs) deletion Pathogenic rs797045289 GRCh38 Chromosome X, 25010283: 25010283
45 ARX NM_139058.2(ARX): c.562_563delGCinsTA (p.Ala188Ter) indel Pathogenic rs797045303 GRCh37 Chromosome X, 25031549: 25031550
46 ARX NM_139058.2(ARX): c.562_563delGCinsTA (p.Ala188Ter) indel Pathogenic rs797045303 GRCh38 Chromosome X, 25013432: 25013433
47 ARX NM_139058.2(ARX) duplication Likely pathogenic rs587776869 GRCh37 Chromosome X, 25031651: 25031686
48 ARX NM_139058.2(ARX) duplication Likely pathogenic rs587776869 GRCh38 Chromosome X, 25013534: 25013569
49 ARX NM_139058.2(ARX): c.409_410insG (p.Glu137Glyfs) duplication Pathogenic rs797045298 GRCh37 Chromosome X, 25031703: 25031703
50 ARX NM_139058.2(ARX): c.409_410insG (p.Glu137Glyfs) duplication Pathogenic rs797045298 GRCh38 Chromosome X, 25013586: 25013586

Expression for X-Linked Lissencephaly with Abnormal Genitalia

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Pathways for X-Linked Lissencephaly with Abnormal Genitalia

GO Terms for X-Linked Lissencephaly with Abnormal Genitalia

Sources for X-Linked Lissencephaly with Abnormal Genitalia

3 CDC
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9 Cosmic
10 dbSNP
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17 ExPASy
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74 UMLS via Orphanet
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