ACCAG
MCID: CRP033
MIFTS: 39

Corpus Callosum, Agenesis of, with Abnormal Genitalia (ACCAG)

Categories: Fetal diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Corpus Callosum, Agenesis of, with Abnormal Genitalia

MalaCards integrated aliases for Corpus Callosum, Agenesis of, with Abnormal Genitalia:

Name: Corpus Callosum, Agenesis of, with Abnormal Genitalia 57 53 74
Proud Syndrome 57 53 59 74 37 13 40 72
Proud Levine Carpenter Syndrome 53 29 6
Acc with Abnormal Genitalia 57 53 74
Proud-Levine-Carpenter Syndrome 59 74
New X-Linked Syndrome with Seizures, Acquired Micrencephaly, and Agenesis of the Corpus Callosum 53
Microcephaly-Corpus Callosum Agenesis-Abnormal Genitalia Syndrome 59
Micrencephaly-Corpus Callosum Agenesis-Abnormal Genitalia 74
Agenesis of the Corpus Callosum, with Abnormal Genitalia 74
Corpus Callosum Agenesis-Abnormal Genitalia Syndrome 59
Acc-Abnormal Genitalia Syndrome 59
Congenital Neurologic Anomalies 72
Nervous System Malformations 44
Accag 74

Characteristics:

Orphanet epidemiological data:

59
corpus callosum agenesis-abnormal genitalia syndrome
Inheritance: X-linked recessive; Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
x-linked

Miscellaneous:
some females are affected


HPO:

32
corpus callosum, agenesis of, with abnormal genitalia:
Inheritance x-linked inheritance


Classifications:



External Ids:

OMIM 57 300004
KEGG 37 H01919
MeSH 44 D009421
ICD10 via Orphanet 34 Q87.8
Orphanet 59 ORPHA2508
MedGen 42 C0796124
UMLS 72 C0497552 C0796124

Summaries for Corpus Callosum, Agenesis of, with Abnormal Genitalia

OMIM : 57 Proud syndrome is an X-linked developmental disorder characterized by agenesis of the corpus callosum, severe mental retardation, seizures, and spasticity. Males are severely affected, whereas females may be unaffected or have a milder phenotype (Proud et al., 1992). Proud syndrome 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 lissencephaly (LISX2; 300215) to Proud syndrome to infantile spasms without brain malformations (EIEE1; 308350) to syndromic (309510) and nonsyndromic (300419) mental retardation (Kato et al., 2004; Wallerstein et al., 2008). (300004)

MalaCards based summary : Corpus Callosum, Agenesis of, with Abnormal Genitalia, also known as proud syndrome, is related to central nervous system malformation and genetic central nervous system malformation, and has symptoms including constitutional symptom An important gene associated with Corpus Callosum, Agenesis of, with Abnormal Genitalia is ARX (Aristaless Related Homeobox). The drugs Abacavir and Lamivudine have been mentioned in the context of this disorder. Affiliated tissues include brain, eye and testis, and related phenotypes are agenesis of corpus callosum and seizures

NIH Rare Diseases : 53 Proud syndrome is a rare neurological condition that is primarily characterized by severe intellectual disability, agenesis of the corpus callosum, seizures, and spasticity. It usually occurs in males; when it occurs in females, the signs and symptoms are often less severe. Proud syndrome is caused by changes (mutations) in the ARX gene and is inherited in an X-linked recessive manner. Treatment is based on the signs and symptoms present in each person.

KEGG : 37
Proud syndrome is a syndromic X-linked mental retardation, characterized by agenesis of the corpus callosum, and abnormal genitalia. ARX is considered to have an important role in neuronal proliferation, interneuronal migration and differentiation in the embryonic brain, and also in the differentiation of the testis. Phenotypes associated with ARX mutations include both brain malformation and non-malformation syndromes. Premature termination mutations and missense mutations in the homeobox domain cause malformation syndromes such as Proud syndrome.

UniProtKB/Swiss-Prot : 74 Agenesis of the corpus callosum, with abnormal genitalia: A X-linked syndrome with variable expression in females. It is characterized by agenesis of corpus callosum, mental retardation and seizures. Manifestations in surviving males include severe acquired micrencephaly, mental retardation, limb contractures, scoliosis, tapered fingers with hyperconvex nails, a characteristic face with large eyes, prominent supraorbital ridges, synophrys, optic atrophy, broad alveolar ridges, and seizures. Urologic anomalies include renal dysplasia, cryptorchidism, and hypospadias.

Related Diseases for Corpus Callosum, Agenesis of, with Abnormal Genitalia

Diseases related to Corpus Callosum, Agenesis of, with Abnormal Genitalia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 147)
# Related Disease Score Top Affiliating Genes
1 central nervous system malformation 12.5
2 genetic central nervous system malformation 12.3
3 other syndrome with a central nervous system malformation as major feature 12.3
4 genetic non-syndromic central nervous system malformation 12.3
5 genetic syndrome with a central nervous system malformation as major feature 12.3
6 syndrome with a central nervous system malformation as major feature 12.3
7 non-syndromic central nervous system malformation 12.3
8 ectodermal dysplasia, hypohidrotic, with hypothyroidism and agenesis of the corpus callosum 11.7
9 scalp syndrome 11.7
10 x-linked lissencephaly with abnormal genitalia 11.3
11 hydrolethalus syndrome 1 11.2
12 meckel syndrome, type 1 11.2
13 lissencephaly, x-linked, 2 11.2
14 mental retardation, x-linked, with or without seizures, arx-related 11.2
15 epileptic encephalopathy, early infantile, 1 11.2
16 partington x-linked mental retardation syndrome 11.2
17 spondylometaphyseal dysplasia, sedaghatian type 11.1
18 meckel syndrome, type 7 11.1
19 acromelic frontonasal dysostosis 11.1
20 microcephaly, postnatal progressive, with seizures and brain atrophy 11.1
21 west syndrome 11.1
22 dandy-walker malformation with intellectual disability, basal ganglia disease and seizures 11.1
23 microcephaly brain defect spasticity hypernatremia 11.1
24 morse-rawnsley-sargent syndrome 11.1
25 craniosynostosis with fibular aplasia 10.5
26 cryptorchidism, unilateral or bilateral 10.5
27 3-methylglutaconic aciduria, type iii 10.5
28 coffin-lowry syndrome 10.5
29 opitz-kaveggia syndrome 10.5
30 scoliosis 10.5
31 hypospadias 10.5
32 spastic quadriplegia 10.5
33 visual epilepsy 10.5
34 locked-in syndrome 10.5
35 quadriplegia 10.5
36 seizure disorder 10.5
37 renal dysplasia 10.5
38 hydrocephalus 10.4
39 congenital hydrocephalus 10.4
40 neural tube defects 10.3
41 holoprosencephaly 10.3
42 myelomeningocele 10.2
43 anencephaly 10.2
44 encephalocele 10.1
45 down syndrome 10.0
46 holoprosencephaly 1 10.0
47 hydrocephalus, congenital, 1 10.0
48 lissencephaly 10.0
49 meningocele 10.0
50 ectodermal dysplasia 10.0

Graphical network of the top 20 diseases related to Corpus Callosum, Agenesis of, with Abnormal Genitalia:



Diseases related to Corpus Callosum, Agenesis of, with Abnormal Genitalia

Symptoms & Phenotypes for Corpus Callosum, Agenesis of, with Abnormal Genitalia

Human phenotypes related to Corpus Callosum, Agenesis of, with Abnormal Genitalia:

59 32 (show all 39)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 agenesis of corpus callosum 59 32 hallmark (90%) Very frequent (99-80%) HP:0001274
2 seizures 59 32 hallmark (90%) Very frequent (99-80%) HP:0001250
3 spasticity 59 32 hallmark (90%) Very frequent (99-80%) HP:0001257
4 microcephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000252
5 short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0004322
6 intellectual disability, severe 59 32 hallmark (90%) Very frequent (99-80%) HP:0010864
7 severe global developmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0011344
8 nystagmus 59 32 frequent (33%) Frequent (79-30%) HP:0000639
9 scoliosis 59 32 frequent (33%) Frequent (79-30%) HP:0002650
10 coarse facial features 59 32 frequent (33%) Frequent (79-30%) HP:0000280
11 protruding ear 59 32 frequent (33%) Frequent (79-30%) HP:0000411
12 strabismus 59 32 frequent (33%) Frequent (79-30%) HP:0000486
13 generalized hirsutism 59 32 frequent (33%) Frequent (79-30%) HP:0002230
14 abnormality of the hip bone 59 32 frequent (33%) Frequent (79-30%) HP:0003272
15 abnormal hair pattern 59 32 frequent (33%) Frequent (79-30%) HP:0010720
16 tetraplegia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002445
17 inguinal hernia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000023
18 renal hypoplasia/aplasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0008678
19 cerebral cortical atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0002120
20 hypospadias 59 32 occasional (7.5%) Occasional (29-5%) HP:0000047
21 renal dysplasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000110
22 high palate 32 HP:0000218
23 prominent supraorbital ridges 32 HP:0000336
24 global developmental delay 32 HP:0001263
25 visual impairment 32 HP:0000505
26 optic atrophy 32 HP:0000648
27 neonatal hypotonia 32 HP:0001319
28 spastic tetraplegia 32 HP:0002510
29 broad alveolar ridges 32 HP:0000187
30 cryptorchidism 32 HP:0000028
31 intellectual disability, progressive 32 HP:0006887
32 low anterior hairline 32 HP:0000294
33 synophrys 32 HP:0000664
34 tapered finger 32 HP:0001182
35 hirsutism 32 HP:0001007
36 hyperconvex nail 32 HP:0001795
37 abnormally large globe 32 HP:0001090
38 overlapping toe 32 HP:0001845
39 limb joint contracture 32 HP:0003121

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus
visual impairment
optic atrophy
strabismus
synophrys
more
Head And Neck Head:
prominent supraorbital ridges
microcephaly

Growth Height:
short stature

Skin Nails Hair Hair:
low anterior hairline
synophrys
hirsutism

Head And Neck Face:
coarse facies

Skeletal Feet:
tapered digits
overlapping toes

Head And Neck Ears:
prominent ears
auditory impairment

Genitourinary Kidneys:
small kidney (reported in 1 patient)

Skeletal Spine:
scoliosis

Neurologic Central Nervous System:
neonatal hypotonia
agenesis of the corpus callosum
developmental delay, severe
mental retardation, severe
spastic quadriplegia, progressive
more
Genitourinary External Genitalia Male:
cryptorchidism
hypospadias

Head And Neck Mouth:
high-arched palate

Skeletal Hands:
tapered digits

Skin Nails Hair Nails:
hyperconvex nails

Skeletal:
contractures

Clinical features from OMIM:

300004

UMLS symptoms related to Corpus Callosum, Agenesis of, with Abnormal Genitalia:


constitutional symptom

Drugs & Therapeutics for Corpus Callosum, Agenesis of, with Abnormal Genitalia

Drugs for Corpus Callosum, Agenesis of, with Abnormal Genitalia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 18)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Abacavir Approved, Investigational Phase 2 136470-78-5 65140 441300
2
Lamivudine Approved, Investigational Phase 2 134678-17-4 60825
3
Zidovudine Approved Phase 2 30516-87-1 35370
4
Adenosine Approved, Investigational Phase 1, Phase 2 58-61-7 60961
5
Emtricitabine Approved, Investigational Phase 1, Phase 2 143491-57-0 60877
6
Tenofovir Experimental, Investigational Phase 1, Phase 2 147127-20-6 464205
7 Pharmaceutical Solutions Phase 2
8 Antimetabolites Phase 2
9 Protein Kinase Inhibitors Phase 2
10 Janus Kinase Inhibitors Phase 2
11 Nucleic Acid Synthesis Inhibitors Phase 1, Phase 2
12 Reverse Transcriptase Inhibitors Phase 1, Phase 2
13 Anti-HIV Agents Phase 1, Phase 2
14 interferons Phase 1, Phase 2
15 Antiviral Agents Phase 1, Phase 2
16 Anti-Retroviral Agents Phase 1, Phase 2
17 Interleukin 1 Receptor Antagonist Protein Phase 1, Phase 2
18 Antirheumatic Agents Phase 1, Phase 2

Interventional clinical trials:

(show all 13)
# Name Status NCT ID Phase Drugs
1 A Randomized, Double-Blind, Two-Part, Parallel-Group, Comparative Study to Evaluate Blood Folate Levels in Women Taking an Oral Contraceptive With and Without Folic Acid Withdrawn NCT00301587 Phase 3 Norgestimate-ethinyl estradiol, with or without folic acid
2 A Pilot Clinical Trial of Reverse Transcriptase Inhibitors in Children With Aicardi-Goutières Syndrome (AGS) Completed NCT02363452 Phase 2 Reverse transcriptase inhibitors: Zidovudine, Lamivudine, Abacavir
3 Janus Kinase Inhibitor (Baricitinib) for Aicardi Goutières Syndrome Recruiting NCT03921554 Phase 2 Baricitinib
4 Reverse Transcriptase Inhibitors in Aicardi Goutières Syndrome Active, not recruiting NCT03304717 Phase 1, Phase 2 Tenofovir (TDF) and Emtricitabine (FTC)
5 A Randomized, Double-Blind, Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of FLX-787-ODT for Treatment of Muscle Cramps in Adult Subjects With Charcot-Marie-Tooth Disease Terminated NCT03254199 Phase 2 FLX-787-ODT (orally disintegrating tablet);Placebo ODT
6 A Long-Term Outcome Study With the IL-1 Receptor Antagonist Anakinra/Kineret in Patients With Neonatal Onset Multisystem Inflammatory Disease (NOMID/CINCA Syndrome) A Therapeutic Approach to Study the Pathogenesis of This Disease Terminated NCT00069329 Phase 1, Phase 2 anakinra
7 Assessment of the Prevalence and Mutational Spectrum of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome and Cerebello-oculo-renal Syndromes Completed NCT00873678
8 National Health Survey of Gulf War Era Veterans and Their Families - Phase III Physical Examinations Completed NCT00032461
9 Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies Recruiting NCT03059420
10 Studies of Natural History, Pathogenesis, and Outcomes in Autoimmune and Inflammatory Diseases Including Juvenile Dermatomyositis Recruiting NCT00059748
11 Clinical Utility of Prenatal Whole Exome Sequencing Recruiting NCT03482141
12 Compassionate Use Treatment Protocol I4V-MC-JAGA: Treatment of Conditions Expected to Benefit From JAK 1/2 Inhibition: CANDLE, CANDLE-Related Conditions, SAVI and Severe Juvenile Dermatomyositis No longer available NCT01724580 Baricitinib
13 Comparison of Abnormal Cortical Development in Brain Malformations on Postmortem Imaging With Autopsy Withdrawn NCT00686530

Search NIH Clinical Center for Corpus Callosum, Agenesis of, with Abnormal Genitalia

Cochrane evidence based reviews: nervous system malformations

Genetic Tests for Corpus Callosum, Agenesis of, with Abnormal Genitalia

Genetic tests related to Corpus Callosum, Agenesis of, with Abnormal Genitalia:

# Genetic test Affiliating Genes
1 Proud Levine Carpenter Syndrome 29 ARX

Anatomical Context for Corpus Callosum, Agenesis of, with Abnormal Genitalia

MalaCards organs/tissues related to Corpus Callosum, Agenesis of, with Abnormal Genitalia:

41
Brain, Eye, Testis, Bone, Kidney

Publications for Corpus Callosum, Agenesis of, with Abnormal Genitalia

Articles related to Corpus Callosum, Agenesis of, with Abnormal Genitalia:

# Title Authors PMID Year
1
Mutations of ARX are associated with striking pleiotropy and consistent genotype-phenotype correlation. 38 8 71
14722918 2004
2
New X-linked syndrome with seizures, acquired micrencephaly, and agenesis of the corpus callosum. 8 71
1605226 1992
3
Distinct DNA binding and transcriptional repression characteristics related to different ARX mutations. 71
22252899 2012
4
Targeted loss of Arx results in a developmental epilepsy mouse model and recapitulates the human phenotype in heterozygous females. 8
19439424 2009
5
Expansion of the ARX spectrum. 8
18462864 2008
6
X-linked lissencephaly with absent corpus callosum and ambiguous genitalia (XLAG): clinical, magnetic resonance imaging, and neuropathological findings. 8
11891829 2002
7
Mutations in the nuclear localization sequence of the Aristaless related homeobox; sequestration of mutant ARX with IPO13 disrupts normal subcellular distribution of the transcription factor and retards cell division. 38
20148114 2010

Variations for Corpus Callosum, Agenesis of, with Abnormal Genitalia

ClinVar genetic disease variations for Corpus Callosum, Agenesis of, with Abnormal Genitalia:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 ARX NM_139058.3(ARX): c.998C> A (p.Thr333Asn) single nucleotide variant Pathogenic rs104894745 X:25031114-25031114 X:25012997-25012997
2 ARX NM_139058.3(ARX): c.1170C> T (p.Gly390=) single nucleotide variant Conflicting interpretations of pathogenicity rs761632870 X:25025506-25025506 X:25007389-25007389
3 ARX NM_139058.3(ARX): c.187G> A (p.Ala63Thr) single nucleotide variant Uncertain significance X:25033668-25033668 X:25015551-25015551

UniProtKB/Swiss-Prot genetic disease variations for Corpus Callosum, Agenesis of, with Abnormal Genitalia:

74
# Symbol AA change Variation ID SNP ID
1 ARX p.Thr333Asn VAR_033261 rs104894745

Expression for Corpus Callosum, Agenesis of, with Abnormal Genitalia

Search GEO for disease gene expression data for Corpus Callosum, Agenesis of, with Abnormal Genitalia.

Pathways for Corpus Callosum, Agenesis of, with Abnormal Genitalia

GO Terms for Corpus Callosum, Agenesis of, with Abnormal Genitalia

Sources for Corpus Callosum, Agenesis of, with Abnormal Genitalia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
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28 GO
29 GTR
30 HGMD
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32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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