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 49 24
X-Linked Lissencephaly with Ambiguous Genitalia 49 24
Xlisg 49 24
X-Linked Lissencephaly-Agenesis of the Corpus Callosum-Genital Anomalies Syndrome 49
X-Linked Lissencephaly - Agenesis of the Corpus Callosum - Genital Anomalies 49
X-Linked Lissencephaly-Corpus Callosum Agenesis-Genital Anomalies Syndrome 49
Lissencephaly, X-Linked, with Ambiguous Genitalia 49
Hydranencephaly with Abnormal Genitalia 49
Chromosome Xq26.3 Duplication Syndrome 69
Lissencephaly, X-Linked, 2 69
Lissencephaly, X-Linked 2 49
Lissencephaly 2, X-Linked 28
X-Linked Lissencephaly 2 24
Xlag Syndrome 49
Xlag Syndrome 49
Lisx2 24
Xlag 24

Characteristics:

HPO:

31
x-linked lissencephaly with abnormal genitalia:
Mortality/Aging death in infancy


Classifications:



Summaries for X-Linked Lissencephaly with Abnormal Genitalia

NIH Rare Diseases : 49 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. Last updated: 6/17/2004

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 cryptorchidism, ambiguous genitalia and microcephaly. An important gene associated with X-Linked Lissencephaly with Abnormal Genitalia is ARX (Aristaless Related Homeobox). Affiliated tissues include brain, cortex and thalamus.

Genetics Home Reference : 24 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 11.8
2 lissencephaly, x-linked, 2 11.7
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:

31 (show all 20)
# Description HPO Frequency HPO Source Accession
1 cryptorchidism 31 hallmark (90%) HP:0000028
2 ambiguous genitalia 31 hallmark (90%) HP:0000062
3 microcephaly 31 hallmark (90%) HP:0000252
4 micrognathia 31 occasional (7.5%) HP:0000347
5 hypohidrosis 31 frequent (33%) HP:0000966
6 intellectual disability 31 hallmark (90%) HP:0001249
7 seizures 31 hallmark (90%) HP:0001250
8 muscular hypotonia 31 frequent (33%) HP:0001252
9 spasticity 31 occasional (7.5%) HP:0001257
10 global developmental delay 31 hallmark (90%) HP:0001263
11 agenesis of corpus callosum 31 hallmark (90%) HP:0001274
12 pachygyria 31 hallmark (90%) HP:0001302
13 ventricular septal defect 31 occasional (7.5%) HP:0001629
14 patent ductus arteriosus 31 occasional (7.5%) HP:0001643
15 exocrine pancreatic insufficiency 31 occasional (7.5%) HP:0001738
16 malabsorption 31 frequent (33%) HP:0002024
17 ventriculomegaly 31 frequent (33%) HP:0002119
18 aganglionic megacolon 31 occasional (7.5%) HP:0002251
19 hypoplasia of penis 31 hallmark (90%) HP:0008736
20 prominent forehead 31 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 28 ARX

Anatomical Context for X-Linked Lissencephaly with Abnormal Genitalia

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

38
Brain, Cortex, Thalamus, Skin, Hypothalamus, Testes

Publications for X-Linked Lissencephaly with Abnormal Genitalia

Articles related to X-Linked Lissencephaly with Abnormal Genitalia:

# Title Authors Year
1
Watery diarrhea-hypopotassemia-acidosis syndrome like diarrhea in a case with X-linked lissencephaly with abnormal genitalia. ( 26129807 )
2015
2
Analysis of the hypothalamus in a case of X-linked lissencephaly with abnormal genitalia (XLAG). ( 18842366 )
2009
3
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
4
X-linked lissencephaly with abnormal genitalia as a tangential migration disorder causing intractable epilepsy: proposal for a new term, "interneuronopathy". ( 15921244 )
2005
5
X-linked lissencephaly with abnormal genitalia associated with renal phosphate wasting. ( 15248105 )
2004
6
ARX mutations in X-linked lissencephaly with abnormal genitalia. ( 12874405 )
2003
7
Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans. ( 12379852 )
2002

Variations for X-Linked Lissencephaly with Abnormal Genitalia

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

6 (show all 33)
# 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 ARX, 32-BP DEL, NT420 deletion Pathogenic
3 ARX ARX, 1-BP DEL, 790C deletion Pathogenic
4 ARX NM_139058.2(ARX): c.995G> A (p.Arg332His) single nucleotide variant Pathogenic rs111033612 GRCh37 Chromosome X, 25031117: 25031117
5 ARX NM_139058.2(ARX): c.1117C> T (p.Gln373Ter) single nucleotide variant Pathogenic rs104894740 GRCh37 Chromosome X, 25028379: 25028379
6 ARX ARX, 1-BP INS, 1188C insertion Pathogenic
7 ARX ARX, EX1-2DEL deletion Pathogenic
8 ARX ARX, 1-BP DEL, 1372G deletion Pathogenic
9 ARX NM_139058.2(ARX): c.1028T> A (p.Leu343Gln) single nucleotide variant Pathogenic rs104894741 GRCh37 Chromosome X, 25031084: 25031084
10 ARX NM_139058.2(ARX): c.1105G> T (p.Glu369Ter) single nucleotide variant Pathogenic rs104894746 GRCh37 Chromosome X, 25028391: 25028391
11 ARX ARX, 1-BP DEL, 617G deletion Pathogenic
12 ARX NM_139058.2(ARX): c.232G> T (p.Glu78Ter) single nucleotide variant Pathogenic rs267606666 GRCh37 Chromosome X, 25031880: 25031880
13 ARX NM_139058.2(ARX) duplication Pathogenic rs398124511 GRCh37 Chromosome X, 25031648: 25031671
14 ARX NM_139058.2(ARX): c.1372delG (p.Ala458Argfs) deletion Pathogenic rs587783187 GRCh37 Chromosome X, 25025304: 25025304
15 ARX NM_139058.2(ARX): c.1414C> T (p.Arg472Ter) single nucleotide variant Pathogenic rs587783189 GRCh38 Chromosome X, 25007145: 25007145
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 GRCh38 Chromosome X, 25013627: 25013660
18 ARX NM_139058.2(ARX): c.617delG (p.Gly206Alafs) deletion Pathogenic rs587783202 GRCh37 Chromosome X, 25031495: 25031495
19 ARX NM_139058.2(ARX): c.995G> T (p.Arg332Leu) single nucleotide variant Pathogenic rs111033612 GRCh38 Chromosome X, 25013000: 25013000
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.1337dupC (p.Pro447Alafs) duplication Pathogenic rs797045291 GRCh37 Chromosome X, 25025339: 25025339
23 ARX NM_139058.2(ARX): c.1164_1165insCAAAG (p.Ala389Glnfs) insertion Pathogenic rs797045290 GRCh38 Chromosome X, 25007394: 25007395
24 ARX NM_139058.2(ARX): c.1096delG (p.Asp366Thrfs) deletion Pathogenic rs797045289 GRCh38 Chromosome X, 25010283: 25010283
25 ARX NM_139058.2(ARX): c.562_563delGCinsTA (p.Ala188Ter) indel Pathogenic rs797045303 GRCh38 Chromosome X, 25013432: 25013433
26 ARX NM_139058.2(ARX): c.409_410insG (p.Glu137Glyfs) duplication Pathogenic rs797045298 GRCh38 Chromosome X, 25013586: 25013586
27 ARX NM_139058.2(ARX) duplication Pathogenic rs587783198 GRCh38 Chromosome X, 25013660: 25013683
28 ARX NM_139058.2(ARX): c.304_305ins21 (p.?) insertion Pathogenic rs797045296 GRCh37 Chromosome X, 25031807: 25031808
29 ARX NM_139058.2(ARX): c.1120-82_1469dup duplication Pathogenic
30 ARX NM_139058.2(ARX): c.790delC (p.Arg264Glyfs) deletion Pathogenic rs886043552 GRCh37 Chromosome X, 25031322: 25031322
31 ARX NM_139058.2(ARX): c.614_642del29 (p.Leu205Profs) deletion Pathogenic rs886043728 GRCh37 Chromosome X, 25031470: 25031498
32 ARX NM_139058.2(ARX): c.1535_1549delTGGCATCGGGCGCCCinsGGCGCAG (p.Val512Glyfs) indel Pathogenic GRCh37 Chromosome X, 25022927: 25022941
33 ARX NM_139058.2(ARX): c.1141delG (p.Ala381Profs) deletion Pathogenic GRCh37 Chromosome X, 25025535: 25025535

Expression for X-Linked Lissencephaly with Abnormal Genitalia

Search GEO for disease gene expression data for X-Linked Lissencephaly with Abnormal Genitalia.

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

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