Lissencephaly, X-Linked, 2 disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

MCID: LSS037 MIFTS: 30	Lissencephaly, X-Linked, 2 Categories: Genetic diseases, Neuronal diseases, Endocrine diseases, Fetal diseases, Rare diseases, Reproductive diseases
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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:

MalaCards categories:
Global: Genetic diseases Fetal diseases Rare diseases
Anatomical: Neuronal diseases Endocrine diseases Reproductive diseases

See all MalaCards categories (disease lists)

ICD10: ³⁴

Congenital malformations, deformations and chromosomal abnormalities

Congenital malformations of the nervous system

Other congenital malformations of brain

Other reduction deformities of brain

Orphanet: ⁵⁹

Rare neurological diseases

Rare endocrine diseases

Developmental anomalies during embryogenesis

External Ids:

OMIM ⁵⁷ 300215

Orphanet ⁵⁹ ORPHA452

UMLS via Orphanet ⁷⁴ C1846171

ICD10 via Orphanet ³⁴ Q04.3

MedGen ⁴² C1846171 C1846172

MeSH ⁴⁴ D054082

UMLS ⁷³ C1846171 C3891556

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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.

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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
1	x-linked lissencephaly with abnormal genitalia	11.4
2	lissencephaly	11.3
3	chromosome xq26.3 duplication syndrome	11.2

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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	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

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Drugs & Therapeutics for Lissencephaly, X-Linked, 2

Search Clinical Trials , NIH Clinical Center for Lissencephaly, X-Linked, 2

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Genetic Tests for Lissencephaly, X-Linked, 2

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Anatomical Context for Lissencephaly, X-Linked, 2

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

⁴¹

Brain, Testes, Cortex, Skin

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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 )	Minocha P....Sitaraman S.	2017
2	Association between X-linked lissencephaly with ambiguous genitalia syndrome and lenticulostriate vasculopathy in neonate. ( 18412232 )	JagA8a M....Kwinta P.	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 )	Colombo E....Broccoli V.	2007
4	X-linked lissencephaly with ambiguous genitalia: delineation of further case. ( 10982975 )	Ogata T....Hata J.I.	2000

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Genes for Lissencephaly, X-Linked, 2

Genes related to Lissencephaly, X-Linked, 2 (1 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubmedIds
1	ARX	Aristaless Related Homeobox	Protein Coding	1578.27	Molecular basis known ⁵⁷ Pathogenic ⁶ Causative germline mutation (loss of function) ⁵⁹ Causative variation ⁷⁵ GeneCards inferred via : Disorders Variants (show sections)	12379852 12874405 22252899 (more) 14722918 11891829

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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

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Expression for Lissencephaly, X-Linked, 2

Search GEO for disease gene expression data for Lissencephaly, X-Linked, 2.

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Pathways for Lissencephaly, X-Linked, 2

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GO Terms for Lissencephaly, X-Linked, 2

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Sources for Lissencephaly, X-Linked, 2

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