NEDBEH
MCID: NRD024
MIFTS: 32

Neurodevelopmental Disorder with or Without Anomalies of the Brain, Eye, or Heart (NEDBEH)

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

Aliases & Classifications for Neurodevelopmental Disorder with or Without Anomalies of the...

MalaCards integrated aliases for Neurodevelopmental Disorder with or Without Anomalies of the Brain, Eye, or Heart:

Name: Neurodevelopmental Disorder with or Without Anomalies of the Brain, Eye, or Heart 57 43 72 29 6 17
Rere-Related Neurodevelopmental Syndrome 43 58 36
Nedbeh 57 43 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
onset in infancy
de novo mutation
highly variable extraneurologic manifestations that occur in less than 50% of patients


HPO:

31
neurodevelopmental disorder with or without anomalies of the brain, eye, or heart:
Inheritance autosomal dominant inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


Summaries for Neurodevelopmental Disorder with or Without Anomalies of the...

MedlinePlus Genetics : 43 Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH) is a neurological disorder that can also affect many other body systems. This condition primarily affects neurological development, causing intellectual disability, delayed development of speech and motor skills (such as sitting and walking), or autism spectrum disorder, which is a condition that affects communication and social interaction. Some affected individuals have additional neurological features, such as weak muscle tone (hypotonia), behavioral problems, and seizures.NEDBEH can affect development of many other parts of the body. Some affected individuals have abnormalities of brain structures, such as the tissue that connects the left and right halves of the brain (the corpus callosum), a tissue called white matter, the fluid-filled cavities (ventricles) near the center of the brain, or a structure at the back of the brain known as the cerebellar vermis. Eye abnormalities that can occur include a gap or hole in one of the structures of the eye (coloboma), underdevelopment (hypoplasia) or breakdown (atrophy) of the nerves that carry information from the eyes to the brain (optic nerves), or unusually small eyeballs (microphthalmia). These eye problems can cause vision impairment. Some affected individuals have heart defects, most commonly ventricular septal defect, which is a hole in the muscular wall (septum) that separates the right and left sides of the heart's lower chambers.Less commonly, other systems are affected in NEDBEH, including the kidneys and inner ear. Problems with the inner ear can lead to hearing impairment (sensorineural hearing loss).The signs and symptoms in some people with NEDBEH resemble those of another condition known as CHARGE syndrome; however, people with NEDBEH do not have changes in the gene associated with CHARGE syndrome.

MalaCards based summary : Neurodevelopmental Disorder with or Without Anomalies of the Brain, Eye, or Heart, also known as rere-related neurodevelopmental syndrome, is related to rere-related disorders and chromosome 1p36 deletion syndrome. An important gene associated with Neurodevelopmental Disorder with or Without Anomalies of the Brain, Eye, or Heart is RERE (Arginine-Glutamic Acid Dipeptide Repeats). Affiliated tissues include eye, brain and heart, and related phenotypes are intellectual disability and global developmental delay

OMIM® : 57 Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart is an autosomal dominant syndrome characterized by onset in infancy of developmental delay, intellectual disability, and behavioral disorders, such as autism spectrum disorders. About half of patients have additional abnormalities, most commonly involving the eye, heart, and genitourinary system. The phenotype is reminiscent of that observed in patients with 1p36 deletion syndrome (607872); RERE is located in the proximal 1p36 critical region (summary by Fregeau et al., 2016). (616975) (Updated 20-May-2021)

KEGG : 36 RERE-related neurodevelopmental syndrome, also known as neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH), is a rare autosomal dominant disorder. Patients with intellectual disability, developmental delay, and autism spectrum disorder who carry mutations in RERE have been described. RERE is a widely-expressed nuclear receptor coregulator that positively regulates retinoic acid signaling.

UniProtKB/Swiss-Prot : 72 Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart: An autosomal dominant syndrome characterized by developmental delay, intellectual disability, brain anomalies, and neurological abnormalities including seizures, hypotonia, and behavioral problems such as autism spectrum disorders. Brain anomalies include abnormalities and/or thinning of the corpus callosum, diminished white matter volume, abnormal cerebellar vermis, and ventriculomegaly. Congenital defects of the eye, heart and genitourinary system are present in half of the patients.

Related Diseases for Neurodevelopmental Disorder with or Without Anomalies of the...

Diseases related to Neurodevelopmental Disorder with or Without Anomalies of the Brain, Eye, or Heart via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 rere-related disorders 11.7
2 chromosome 1p36 deletion syndrome 11.4

Symptoms & Phenotypes for Neurodevelopmental Disorder with or Without Anomalies of the...

Human phenotypes related to Neurodevelopmental Disorder with or Without Anomalies of the Brain, Eye, or Heart:

58 31 (show top 50) (show all 94)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
2 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
3 intrauterine growth retardation 58 31 very rare (1%) Frequent (79-30%) HP:0001511
4 postnatal growth retardation 58 31 frequent (33%) Frequent (79-30%) HP:0008897
5 brain imaging abnormality 58 31 frequent (33%) Frequent (79-30%) HP:0410263
6 hypotonia 31 very rare (1%) HP:0001252
7 frontal bossing 58 31 very rare (1%) Occasional (29-5%) HP:0002007
8 scoliosis 58 31 very rare (1%) Occasional (29-5%) HP:0002650
9 ptosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000508
10 dysphagia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002015
11 self-injurious behavior 58 31 occasional (7.5%) Occasional (29-5%) HP:0100716
12 hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000365
13 hip dysplasia 58 31 very rare (1%) Occasional (29-5%) HP:0001385
14 abnormal facial shape 58 31 occasional (7.5%) Occasional (29-5%) HP:0001999
15 anteverted nares 58 31 very rare (1%) Occasional (29-5%) HP:0000463
16 optic atrophy 58 31 very rare (1%) Occasional (29-5%) HP:0000648
17 gastroesophageal reflux 58 31 very rare (1%) Occasional (29-5%) HP:0002020
18 cryptorchidism 58 31 very rare (1%) Occasional (29-5%) HP:0000028
19 attention deficit hyperactivity disorder 58 31 very rare (1%) Occasional (29-5%) HP:0007018
20 micrognathia 58 31 very rare (1%) Occasional (29-5%) HP:0000347
21 epicanthus 58 31 very rare (1%) Occasional (29-5%) HP:0000286
22 myopia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000545
23 iris coloboma 58 31 occasional (7.5%) Occasional (29-5%) HP:0000612
24 low-set, posteriorly rotated ears 58 31 occasional (7.5%) Occasional (29-5%) HP:0000368
25 choanal atresia 58 31 very rare (1%) Occasional (29-5%) HP:0000453
26 chorioretinal coloboma 58 31 occasional (7.5%) Occasional (29-5%) HP:0000567
27 microphthalmia 58 31 very rare (1%) Occasional (29-5%) HP:0000568
28 vesicoureteral reflux 58 31 very rare (1%) Occasional (29-5%) HP:0000076
29 ventriculomegaly 58 31 very rare (1%) Occasional (29-5%) HP:0002119
30 hypospadias 58 31 very rare (1%) Occasional (29-5%) HP:0000047
31 ventricular septal defect 58 31 very rare (1%) Occasional (29-5%) HP:0001629
32 blepharophimosis 58 31 very rare (1%) Occasional (29-5%) HP:0000581
33 astigmatism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000483
34 hypoplasia of the corpus callosum 58 31 very rare (1%) Occasional (29-5%) HP:0002079
35 poor suck 58 31 occasional (7.5%) Occasional (29-5%) HP:0002033
36 autistic behavior 58 31 very rare (1%) Occasional (29-5%) HP:0000729
37 cerebellar vermis hypoplasia 58 31 very rare (1%) Occasional (29-5%) HP:0001320
38 peters anomaly 58 31 very rare (1%) Occasional (29-5%) HP:0000659
39 cerebral visual impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0100704
40 esotropia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000565
41 exotropia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000577
42 broad eyebrow 58 31 very rare (1%) Occasional (29-5%) HP:0011229
43 cns demyelination 58 31 occasional (7.5%) Occasional (29-5%) HP:0007305
44 anisometropia 58 31 occasional (7.5%) Occasional (29-5%) HP:0012803
45 abnormal cranial nerve physiology 58 31 occasional (7.5%) Occasional (29-5%) HP:0031910
46 seizure 31 very rare (1%) HP:0001250
47 strabismus 58 31 very rare (1%) Occasional (29-5%) HP:0000486
48 feeding difficulties 58 31 very rare (1%) Frequent (79-30%) HP:0011968
49 macrocephaly 31 very rare (1%) HP:0000256
50 dysarthria 31 very rare (1%) HP:0001260

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Face:
frontal bossing
micrognathia

Head And Neck Nose:
anteverted nares

Growth Height:
short stature

Genitourinary Internal Genitalia Male:
cryptorchidism

Head And Neck Ears:
low-set ears
posteriorly rotated ears

Genitourinary External Genitalia Male:
hypospadias

Muscle Soft Tissue:
hypotonia

Genitourinary Kidneys:
cystic kidney

Neurologic Central Nervous System:
dysarthria
global developmental delay
ventriculomegaly
cerebellar vermis hypoplasia
thin corpus callosum
more
Head And Neck Eyes:
optic atrophy
strabismus
microphthalmia
blepharophimosis
coloboma
more
Abdomen Gastrointestinal:
gastroesophageal reflux
poor feeding

Growth Other:
intrauterine growth retardation
poor postnatal growth

Genitourinary Bladder:
vesicoureteral reflux

Cardiovascular Heart:
ventricular septal defect
congenital heart defects (40% of patients)

Neurologic Behavioral Psychiatric Manifestations:
behavioral abnormalities
autism spectrum disorder

Clinical features from OMIM®:

616975 (Updated 20-May-2021)

Drugs & Therapeutics for Neurodevelopmental Disorder with or Without Anomalies of the...

Search Clinical Trials , NIH Clinical Center for Neurodevelopmental Disorder with or Without Anomalies of the Brain, Eye, or Heart

Genetic Tests for Neurodevelopmental Disorder with or Without Anomalies of the...

Genetic tests related to Neurodevelopmental Disorder with or Without Anomalies of the Brain, Eye, or Heart:

# Genetic test Affiliating Genes
1 Neurodevelopmental Disorder with or Without Anomalies of the Brain, Eye, or Heart 29 RERE

Anatomical Context for Neurodevelopmental Disorder with or Without Anomalies of the...

MalaCards organs/tissues related to Neurodevelopmental Disorder with or Without Anomalies of the Brain, Eye, or Heart:

40
Eye, Brain, Heart, Pancreas, Pons, Tongue, Kidney

Publications for Neurodevelopmental Disorder with or Without Anomalies of the...

Articles related to Neurodevelopmental Disorder with or Without Anomalies of the Brain, Eye, or Heart:

# Title Authors PMID Year
1
De Novo Mutations of RERE Cause a Genetic Syndrome with Features that Overlap Those Associated with Proximal 1p36 Deletions. 6 57
27087320 2016
2
Novel genetic causes for cerebral visual impairment. 6 57
26350515 2016
3
Excess of rare, inherited truncating mutations in autism. 57
25961944 2015
4
Mouse model reveals the role of RERE in cerebellar foliation and the migration and maturation of Purkinje cells. 57
24466353 2014
5
An allelic series of mice reveals a role for RERE in the development of multiple organs affected in chromosome 1p36 deletions. 57
23451234 2013
6
RERE deficiency contributes to the development of orofacial clefts in humans and mice. 61
33772547 2021
7
RERE deficiency causes retinal and optic nerve atrophy through degeneration of retinal cells. 61
33742727 2021
8
Genotype-phenotype correlations in individuals with pathogenic RERE variants. 61
29330883 2018

Variations for Neurodevelopmental Disorder with or Without Anomalies of the...

ClinVar genetic disease variations for Neurodevelopmental Disorder with or Without Anomalies of the Brain, Eye, or Heart:

6 (show all 40)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 RERE NM_001042681.2(RERE):c.4319A>G (p.Gln1440Arg) SNV Pathogenic 562007 rs1321809020 GRCh37: 1:8418276-8418276
GRCh38: 1:8358216-8358216
2 RERE NM_001042681.2(RERE):c.2249_2270dup (p.Thr758fs) Duplication Pathogenic 236219 rs878853252 GRCh37: 1:8421296-8421297
GRCh38: 1:8361236-8361237
3 RERE NM_001042681.2(RERE):c.3466G>A (p.Gly1156Arg) SNV Pathogenic 236216 rs766951273 GRCh37: 1:8419976-8419976
GRCh38: 1:8359916-8359916
4 RERE NM_001042681.2(RERE):c.3785C>G (p.Pro1262Arg) SNV Pathogenic 236217 rs878853270 GRCh37: 1:8418810-8418810
GRCh38: 1:8358750-8358750
5 RERE NM_001042681.2(RERE):c.4293C>A (p.His1431Gln) SNV Pathogenic 224822 rs869312871 GRCh37: 1:8418302-8418302
GRCh38: 1:8358242-8358242
6 RERE Deletion Pathogenic 562002 GRCh37: 1:8497191-8813784
GRCh38:
7 RERE NM_001042681.2(RERE):c.248dup (p.Ser84fs) Duplication Pathogenic 562003 rs1557461427 GRCh37: 1:8716108-8716109
GRCh38: 1:8656049-8656050
8 RERE NM_001042681.2(RERE):c.3146C>T (p.Pro1049Leu) SNV Pathogenic 235329 rs878853011 GRCh37: 1:8420421-8420421
GRCh38: 1:8360361-8360361
9 RERE NM_001042681.2(RERE):c.4300T>C (p.Ser1434Pro) SNV Pathogenic 562004 rs1557582271 GRCh37: 1:8418295-8418295
GRCh38: 1:8358235-8358235
10 RERE NM_001042681.2(RERE):c.4303C>T (p.His1435Tyr) SNV Pathogenic 562005 rs1557582259 GRCh37: 1:8418292-8418292
GRCh38: 1:8358232-8358232
11 RERE NM_001042681.2(RERE):c.4307_4312TCCACC[3] (p.1436_1437LH[3]) Microsatellite Pathogenic 418456 rs1064793252 GRCh37: 1:8418276-8418277
GRCh38: 1:8358216-8358217
12 RERE NM_001042681.2(RERE):c.4304A>G (p.His1435Arg) SNV Pathogenic/Likely pathogenic 522858 rs1553154130 GRCh37: 1:8418291-8418291
GRCh38: 1:8358231-8358231
13 RERE NM_001042681.2(RERE):c.4304A>T (p.His1435Leu) SNV Likely pathogenic 452391 rs1553154130 GRCh37: 1:8418291-8418291
GRCh38: 1:8358231-8358231
14 RERE NM_001042681.2(RERE):c.3292C>G (p.Leu1098Val) SNV Uncertain significance 562006 rs1215653376 GRCh37: 1:8420275-8420275
GRCh38: 1:8360215-8360215
15 RERE NM_001042681.2(RERE):c.14A>G (p.Lys5Arg) SNV Uncertain significance 545588 rs1553128615 GRCh37: 1:8716343-8716343
GRCh38: 1:8656284-8656284
16 RERE NM_001042681.2(RERE):c.3346C>A (p.Pro1116Thr) SNV Uncertain significance 587517 rs1557585339 GRCh37: 1:8420221-8420221
GRCh38: 1:8360161-8360161
17 RERE NM_001042681.2(RERE):c.2134T>C (p.Ser712Pro) SNV Uncertain significance 638397 rs1570039432 GRCh37: 1:8421433-8421433
GRCh38: 1:8361373-8361373
18 RERE NM_001042681.2(RERE):c.707A>G (p.Tyr236Cys) SNV Uncertain significance 813923 rs1570434132 GRCh37: 1:8616552-8616552
GRCh38: 1:8556493-8556493
19 RERE NM_001042681.2(RERE):c.241A>G (p.Lys81Glu) SNV Uncertain significance 930458 GRCh37: 1:8716116-8716116
GRCh38: 1:8656057-8656057
20 RERE NM_001042681.2(RERE):c.2507C>T (p.Pro836Leu) SNV Uncertain significance 930549 GRCh37: 1:8421060-8421060
GRCh38: 1:8361000-8361000
21 RERE NM_001042681.2(RERE):c.635G>A (p.Gly212Glu) SNV Uncertain significance 930704 GRCh37: 1:8616624-8616624
GRCh38: 1:8556565-8556565
22 RERE NM_001042681.2(RERE):c.3587G>A (p.Arg1196Gln) SNV Uncertain significance 931352 GRCh37: 1:8419855-8419855
GRCh38: 1:8359795-8359795
23 RERE NM_001042681.2(RERE):c.2422C>A (p.Pro808Thr) SNV Uncertain significance 932086 GRCh37: 1:8421145-8421145
GRCh38: 1:8361085-8361085
24 RERE NM_001042681.2(RERE):c.2861C>T (p.Pro954Leu) SNV Uncertain significance 976254 GRCh37: 1:8420706-8420706
GRCh38: 1:8360646-8360646
25 RERE NM_001042681.2(RERE):c.4354G>A (p.Val1452Ile) SNV Uncertain significance 982578 GRCh37: 1:8416292-8416292
GRCh38: 1:8356232-8356232
26 RERE NM_001042681.2(RERE):c.3466G>T (p.Gly1156Trp) SNV Uncertain significance 986414 GRCh37: 1:8419976-8419976
GRCh38: 1:8359916-8359916
27 RERE NM_001042681.2(RERE):c.2462C>T (p.Ser821Leu) SNV Uncertain significance 373226 rs1057518295 GRCh37: 1:8421105-8421105
GRCh38: 1:8361045-8361045
28 RERE NM_001042681.2(RERE):c.3094C>T (p.Pro1032Ser) SNV Uncertain significance 996896 GRCh37: 1:8420473-8420473
GRCh38: 1:8360413-8360413
29 RERE NM_001042681.2(RERE):c.890C>T (p.Pro297Leu) SNV Uncertain significance 1027760 GRCh37: 1:8557579-8557579
GRCh38: 1:8497519-8497519
30 RERE NM_001042681.2(RERE):c.1681_1684del (p.Glu561fs) Deletion Uncertain significance 1031177 GRCh37: 1:8424172-8424175
GRCh38: 1:8364112-8364115
31 RERE NM_001042681.2(RERE):c.2519C>T (p.Ser840Phe) SNV Uncertain significance 1031178 GRCh37: 1:8421048-8421048
GRCh38: 1:8360988-8360988
32 RERE NM_001042681.2(RERE):c.3095C>A (p.Pro1032His) SNV Uncertain significance 1031179 GRCh37: 1:8420472-8420472
GRCh38: 1:8360412-8360412
33 RERE NM_001042681.2(RERE):c.3158C>T (p.Pro1053Leu) SNV Uncertain significance 1031180 GRCh37: 1:8420409-8420409
GRCh38: 1:8360349-8360349
34 RERE NM_001042681.2(RERE):c.3221C>A (p.Ala1074Glu) SNV Uncertain significance 1031181 GRCh37: 1:8420346-8420346
GRCh38: 1:8360286-8360286
35 RERE NM_001042681.2(RERE):c.3479C>T (p.Ala1160Val) SNV Uncertain significance 1031182 GRCh37: 1:8419963-8419963
GRCh38: 1:8359903-8359903
36 RERE NM_001042681.2(RERE):c.3803C>A (p.Thr1268Asn) SNV Uncertain significance 1031183 GRCh37: 1:8418792-8418792
GRCh38: 1:8358732-8358732
37 RERE NM_001042681.2(RERE):c.3999G>C (p.Glu1333Asp) SNV Uncertain significance 1031184 GRCh37: 1:8418596-8418596
GRCh38: 1:8358536-8358536
38 RERE NM_001042681.2(RERE):c.4042G>T (p.Ala1348Ser) SNV Uncertain significance 1031185 GRCh37: 1:8418553-8418553
GRCh38: 1:8358493-8358493
39 RERE NM_001042681.2(RERE):c.2720T>C (p.Leu907Pro) SNV Uncertain significance 1031739 GRCh37: 1:8420847-8420847
GRCh38: 1:8360787-8360787
40 RERE NM_001042681.2(RERE):c.4571C>T (p.Ser1524Leu) SNV Uncertain significance 1031740 GRCh37: 1:8415575-8415575
GRCh38: 1:8355515-8355515

Expression for Neurodevelopmental Disorder with or Without Anomalies of the...

Search GEO for disease gene expression data for Neurodevelopmental Disorder with or Without Anomalies of the Brain, Eye, or Heart.

Pathways for Neurodevelopmental Disorder with or Without Anomalies of the...

GO Terms for Neurodevelopmental Disorder with or Without Anomalies of the...

Sources for Neurodevelopmental Disorder with or Without Anomalies of the...

3 CDC
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9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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28 GO
29 GTR
30 HMDB
31 HPO
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33 ICD10 via Orphanet
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44 MeSH
45 MESH via Orphanet
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56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
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69 Tocris
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