ACCAG
MCID: CRP033
MIFTS: 39

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

Categories: Fetal diseases, Genetic diseases, Neuronal diseases, Rare 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 20 72
Proud Syndrome 57 12 20 58 72 36 13 39 70
Corpus Callosum Agenesis-Abnormal Genitalia Syndrome 12 58 29 6
Acc with Abnormal Genitalia 57 12 20 72
Proud-Levine-Carpenter Syndrome 12 58 72
Microcephaly-Corpus Callosum Agenesis-Abnormal Genitalia Syndrome 12 58
New X-Linked Syndrome with Seizures, Acquired Micrencephaly, and Agenesis of the Corpus Callosum 20
Micrencephaly-Corpus Callosum Agenesis-Abnormal Genitalia 72
Agenesis of the Corpus Callosum, with Abnormal Genitalia 72
Corpus Callosum Agenesis with Abnormal Genitalia 12
Proud Levine Carpenter Syndrome 20
Acc-Abnormal Genitalia Syndrome 58
Congenital Neurologic Anomalies 70
Nervous System Malformations 44
Accag 72

Characteristics:

Orphanet epidemiological data:

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

OMIM®:

57 (Updated 20-May-2021)
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® : 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 (DEE1; 308350) to syndromic (309510) and nonsyndromic (300419) mental retardation (Kato et al., 2004; Wallerstein et al., 2008). (300004) (Updated 20-May-2021)

MalaCards based summary : Corpus Callosum, Agenesis of, with Abnormal Genitalia, also known as proud syndrome, is related to scalp syndrome and lissencephaly, x-linked, 2, 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 testis, bone and spinal cord, and related phenotypes are spasticity and agenesis of corpus callosum

Disease Ontology : 12 A syndrome characterized by agenesis of the corpus callosum, severe intellectual disability, seizures, and spasticity with males showing a severe phenotype and females showing a mild or non-affected phenotype that has material basis in mutation in ARX on chromosome Xp21.3.

GARD : 20 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 : 72 Agenesis of the corpus callosum, with abnormal genitalia: An 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 120)
# Related Disease Score Top Affiliating Genes
1 scalp syndrome 11.2
2 lissencephaly, x-linked, 2 11.2
3 mental retardation, x-linked, with or without seizures, arx-related 11.0
4 developmental and epileptic encephalopathy 1 11.0
5 partington x-linked mental retardation syndrome 11.0
6 hydrolethalus syndrome 1 11.0
7 meckel syndrome, type 1 11.0
8 spondylometaphyseal dysplasia, sedaghatian type 11.0
9 acromelic frontonasal dysostosis 11.0
10 microphthalmia, syndromic 5 11.0
11 west syndrome 11.0
12 craniosynostosis with fibular aplasia 10.5
13 cryptorchidism, unilateral or bilateral 10.5
14 3-methylglutaconic aciduria, type iii 10.5
15 coffin-lowry syndrome 10.5
16 opitz-kaveggia syndrome 10.5
17 scoliosis 10.5
18 hypospadias 10.5
19 spastic quadriplegia 10.5
20 quadriplegia 10.5
21 seizure disorder 10.5
22 renal dysplasia 10.5
23 hydrocephalus 10.5
24 neural tube defects 10.4
25 holoprosencephaly 10.4
26 anencephaly 10.3
27 myelomeningocele 10.3
28 encephalocele 10.2
29 down syndrome 10.1
30 holoprosencephaly 1 10.1
31 hydrocephalus, congenital, 1 10.1
32 lissencephaly 10.1
33 meningocele 10.1
34 microcephaly 10.1
35 chromosomal triplication 10.1
36 aplasia cutis congenita, nonsyndromic 10.0
37 holoprosencephaly 2 10.0
38 joubert syndrome 1 10.0
39 dandy-walker syndrome 10.0
40 schizencephaly 10.0
41 porencephaly 10.0
42 cerebellar hypoplasia 10.0
43 microphthalmia 10.0
44 ventricular septal defect 10.0
45 craniosynostosis 10.0
46 hydranencephaly 10.0
47 congenital hydrocephalus 10.0
48 encephalopathy 10.0
49 neuronal migration disorders 10.0
50 occipital encephalocele 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 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0001257
2 agenesis of corpus callosum 58 31 hallmark (90%) Very frequent (99-80%) HP:0001274
3 microcephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000252
4 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
5 intellectual disability, severe 58 31 hallmark (90%) Very frequent (99-80%) HP:0010864
6 severe global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0011344
7 seizure 31 hallmark (90%) HP:0001250
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 strabismus 58 31 frequent (33%) Frequent (79-30%) HP:0000486
12 abnormality of the hip bone 58 31 frequent (33%) Frequent (79-30%) HP:0003272
13 protruding ear 58 31 frequent (33%) Frequent (79-30%) HP:0000411
14 generalized hirsutism 58 31 frequent (33%) Frequent (79-30%) HP:0002230
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 renal hypoplasia/aplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0008678
19 cerebral cortical atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002120
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 seizures 58 Very frequent (99-80%)
23 high palate 31 HP:0000218
24 global developmental delay 31 HP:0001263
25 prominent supraorbital ridges 31 HP:0000336
26 visual impairment 31 HP:0000505
27 optic atrophy 31 HP:0000648
28 neonatal hypotonia 31 HP:0001319
29 spastic tetraplegia 31 HP:0002510
30 cryptorchidism 31 HP:0000028
31 intellectual disability, progressive 31 HP:0006887
32 low anterior hairline 31 HP:0000294
33 synophrys 31 HP:0000664
34 tapered finger 31 HP:0001182
35 hirsutism 31 HP:0001007
36 hyperconvex nail 31 HP:0001795
37 broad alveolar ridges 31 HP:0000187
38 overlapping toe 31 HP:0001845
39 abnormally large globe 31 HP:0001090
40 limb joint contracture 31 HP:0003121

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Skeletal Spine:
scoliosis

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)

Head And Neck Eyes:
nystagmus
visual impairment
optic atrophy
strabismus
synophrys
more
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 (Updated 20-May-2021)

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
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 Janus Kinase Inhibitors Phase 2
8 Antimetabolites Phase 2
9 Pharmaceutical Solutions 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 Anti-HIV Agents Phase 1, Phase 2
14 interferons Phase 1, Phase 2
15 Dideoxynucleosides Phase 2
16 Interferon Type I Phase 2
17 Antirheumatic Agents Phase 1, Phase 2
18 Interleukin 1 Receptor Antagonist Protein 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 Active, not recruiting NCT03921554 Phase 2 Baricitinib
4 Reverse Transcriptase Inhibitors in Aicardi Goutières Syndrome Not yet recruiting NCT03304717 Phase 1, Phase 2 Tenofovir (TDF) and Emtricitabine (FTC)
5 Inhibition of Reverse Transcription in Type I Interferon Mediated Neuropathology Not yet recruiting NCT04731103 Phase 2 Abacavir (ABC);Lamivudine (3TC);Abacavir (ABC)+Lamivudine (3TC)+Zidovudine (AZT)
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 National Health Survey of Gulf War Era Veterans and Their Families - Phase III Physical Examinations Completed NCT00032461
8 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
9 Clinical Utility of Prenatal Whole Exome Sequencing Recruiting NCT03482141
10 Neurological Abnormalities in SARS-CoV-2 ICU Patients. A Prospective Study. NeuroCOVID Study Recruiting NCT04643548
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 Corpus Callosum Agenesis-Abnormal Genitalia 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
Testis, Bone, Spinal Cord, Heart, 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. 6 61 57
14722918 2004
2
New X-linked syndrome with seizures, acquired micrencephaly, and agenesis of the corpus callosum. 57 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. 57
19439424 2009
5
Expansion of the ARX spectrum. 57
18462864 2008
6
X-linked lissencephaly with absent corpus callosum and ambiguous genitalia (XLAG): clinical, magnetic resonance imaging, and neuropathological findings. 57
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 Position
1 ARX NM_139058.3(ARX):c.998C>A (p.Thr333Asn) SNV Pathogenic 11200 rs104894745 GRCh37: X:25031114-25031114
GRCh38: X:25012997-25012997
2 ARX NM_139058.3(ARX):c.1170C>T (p.Gly390=) SNV Uncertain significance 234531 rs761632870 GRCh37: X:25025506-25025506
GRCh38: X:25007389-25007389
3 ARX NM_139058.3(ARX):c.187G>A (p.Ala63Thr) SNV Uncertain significance 581240 rs769996976 GRCh37: X:25033668-25033668
GRCh38: X:25015551-25015551
4 LOC109610631 , ARX NM_139058.3(ARX):c.441_455dup (p.Ala151_Ala155dup) Duplication not provided 818170 rs750585274 GRCh37: X:25031656-25031657
GRCh38: X:25013539-25013540

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

72
# 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
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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