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 56 52 73
Proud Syndrome 56 52 58 73 36 13 39 71
Proud Levine Carpenter Syndrome 52 29 6
Acc with Abnormal Genitalia 56 52 73
Proud-Levine-Carpenter Syndrome 58 73
New X-Linked Syndrome with Seizures, Acquired Micrencephaly, and Agenesis of the Corpus Callosum 52
Microcephaly-Corpus Callosum Agenesis-Abnormal Genitalia Syndrome 58
Micrencephaly-Corpus Callosum Agenesis-Abnormal Genitalia 73
Agenesis of the Corpus Callosum, with Abnormal Genitalia 73
Corpus Callosum Agenesis-Abnormal Genitalia Syndrome 58
Acc-Abnormal Genitalia Syndrome 58
Congenital Neurologic Anomalies 71
Nervous System Malformations 43
Accag 73

Characteristics:

Orphanet epidemiological data:

58
corpus callosum agenesis-abnormal genitalia syndrome
Inheritance: X-linked recessive; Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
x-linked

Miscellaneous:
some females are affected


HPO:

31
corpus callosum, agenesis of, with abnormal genitalia:
Inheritance x-linked inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


Summaries for Corpus Callosum, Agenesis of, with Abnormal Genitalia

OMIM : 56 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 Zidovudine 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 : 52 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 : 36 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 : 73 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 pettigrew syndrome 11.1
20 holoprosencephaly with fetal akinesia/hypokinesia sequence 11.1
21 acromelic frontonasal dysostosis 11.1
22 microphthalmia, syndromic 5 11.1
23 microcephaly, postnatal progressive, with seizures and brain atrophy 11.1
24 west syndrome 11.1
25 microcephaly brain defect spasticity hypernatremia 11.1
26 craniosynostosis with fibular aplasia 10.5
27 cryptorchidism, unilateral or bilateral 10.5
28 3-methylglutaconic aciduria, type iii 10.5
29 coffin-lowry syndrome 10.5
30 opitz-kaveggia syndrome 10.5
31 scoliosis 10.5
32 hypospadias 10.5
33 spastic quadriplegia 10.5
34 visual epilepsy 10.5
35 locked-in syndrome 10.5
36 quadriplegia 10.5
37 seizure disorder 10.5
38 renal dysplasia 10.5
39 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 dandy-walker syndrome 10.1
46 aplasia cutis congenita, nonsyndromic 10.0
47 down syndrome 10.0
48 holoprosencephaly 1 10.0
49 hydrocephalus, congenital, 1 10.0
50 lissencephaly 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:

58 31 (show all 39)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 agenesis of corpus callosum 58 31 hallmark (90%) Very frequent (99-80%) HP:0001274
2 seizures 58 31 hallmark (90%) Very frequent (99-80%) HP:0001250
3 spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0001257
4 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
5 microcephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000252
6 intellectual disability, severe 58 31 hallmark (90%) Very frequent (99-80%) HP:0010864
7 severe global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0011344
8 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
9 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
10 coarse facial features 58 31 frequent (33%) Frequent (79-30%) HP:0000280
11 protruding ear 58 31 frequent (33%) Frequent (79-30%) HP:0000411
12 strabismus 58 31 frequent (33%) Frequent (79-30%) HP:0000486
13 generalized hirsutism 58 31 frequent (33%) Frequent (79-30%) HP:0002230
14 abnormality of the hip bone 58 31 frequent (33%) Frequent (79-30%) HP:0003272
15 abnormal hair pattern 58 31 frequent (33%) Frequent (79-30%) HP:0010720
16 tetraplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002445
17 inguinal hernia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000023
18 cerebral cortical atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002120
19 renal hypoplasia/aplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0008678
20 hypospadias 58 31 occasional (7.5%) Occasional (29-5%) HP:0000047
21 renal dysplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000110
22 high palate 31 HP:0000218
23 global developmental delay 31 HP:0001263
24 prominent supraorbital ridges 31 HP:0000336
25 cryptorchidism 31 HP:0000028
26 neonatal hypotonia 31 HP:0001319
27 visual impairment 31 HP:0000505
28 optic atrophy 31 HP:0000648
29 spastic tetraplegia 31 HP:0002510
30 broad alveolar ridges 31 HP:0000187
31 intellectual disability, progressive 31 HP:0006887
32 synophrys 31 HP:0000664
33 overlapping toe 31 HP:0001845
34 low anterior hairline 31 HP:0000294
35 tapered finger 31 HP:0001182
36 limb joint contracture 31 HP:0003121
37 hirsutism 31 HP:0001007
38 hyperconvex nail 31 HP:0001795
39 abnormally large globe 31 HP:0001090

Symptoms via clinical synopsis from OMIM:

56
Skeletal Spine:
scoliosis

Head And Neck Head:
prominent supraorbital ridges
microcephaly

Genitourinary External Genitalia Male:
cryptorchidism
hypospadias

Skin Nails Hair Hair:
synophrys
low anterior hairline
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)

Head And Neck Eyes:
nystagmus
visual impairment
optic atrophy
strabismus
synophrys
more
Growth Height:
short stature

Neurologic Central Nervous System:
neonatal hypotonia
agenesis of the corpus callosum
developmental delay, severe
mental retardation, severe
spastic quadriplegia, progressive
more
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 16)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Abacavir Approved, Investigational Phase 2 136470-78-5 65140 441300
2
Zidovudine Approved Phase 2 30516-87-1 35370
3
Lamivudine Approved, Investigational Phase 2 134678-17-4 60825
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 Janus Kinase Inhibitors Phase 2
10 Reverse Transcriptase Inhibitors Phase 1, Phase 2
11 Anti-Retroviral Agents Phase 1, Phase 2
12 Antiviral Agents Phase 1, Phase 2
13 interferons Phase 1, Phase 2
14 Anti-HIV Agents Phase 1, Phase 2
15 Interleukin 1 Receptor Antagonist Protein Phase 1, Phase 2
16 Antirheumatic Agents Phase 1, Phase 2

Interventional clinical trials:

(show all 11)
# 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 NeuroSeq: A Prospective Trial to Evaluate the Diagnostic Yield of Human Whole Genome Sequencing (WGS) Compared to Standard of Care in Adults With Suspected Genetic Neurological Disorders Recruiting NCT04170985
10 Clinical Utility of Prenatal Whole Exome Sequencing Recruiting NCT03482141
11 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:

40
Brain, Eye, Testis, Bone, Kidney, Heart

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. 61 56 6
14722918 2004
2
New X-linked syndrome with seizures, acquired micrencephaly, and agenesis of the corpus callosum. 56 6
1605226 1992
3
Distinct DNA binding and transcriptional repression characteristics related to different ARX mutations. 6
22252899 2012
4
Targeted loss of Arx results in a developmental epilepsy mouse model and recapitulates the human phenotype in heterozygous females. 56
19439424 2009
5
Expansion of the ARX spectrum. 56
18462864 2008
6
X-linked lissencephaly with absent corpus callosum and ambiguous genitalia (XLAG): clinical, magnetic resonance imaging, and neuropathological findings. 56
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. 61
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 Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ARX NM_139058.3(ARX):c.998C>A (p.Thr333Asn)SNV Pathogenic 11200 rs104894745 X:25031114-25031114 X:25012997-25012997
2 ARX NM_139058.3(ARX):c.1170C>T (p.Gly390=)SNV Conflicting interpretations of pathogenicity 234531 rs761632870 X:25025506-25025506 X:25007389-25007389
3 ARX NM_139058.3(ARX):c.187G>A (p.Ala63Thr)SNV Uncertain significance 581240 rs769996976 X:25033668-25033668 X:25015551-25015551

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

73
# 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

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35 IUPHAR
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43 MeSH
44 MESH via Orphanet
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53 NINDS
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56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
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72 UMLS via Orphanet
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