HADDS
MCID: HYP711
MIFTS: 28

Hypotonia, Ataxia, and Delayed Development Syndrome (HADDS)

Categories: Genetic diseases, Neuronal diseases

Aliases & Classifications for Hypotonia, Ataxia, and Delayed Development Syndrome

MalaCards integrated aliases for Hypotonia, Ataxia, and Delayed Development Syndrome:

Name: Hypotonia, Ataxia, and Delayed Development Syndrome 57 72 36 29 6
Hadds 57 72

Characteristics:

OMIM®:

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

Miscellaneous:
onset in infancy
dysmorphic features are variable
de novo mutations (in most patients)


HPO:

31
hypotonia, ataxia, and delayed development syndrome:
Inheritance autosomal dominant inheritance
Onset and clinical course infantile onset neonatal onset


Classifications:



Summaries for Hypotonia, Ataxia, and Delayed Development Syndrome

KEGG : 36 Hypotonia, ataxia, and delayed development syndrome (HADDS) is a complex neurodevelopmental syndrome, characterized by intellectual disability, speech delay, ataxia, and facial dysmorphism. It has been reported that de novo mutations in EBF3 cause HADDS. EBF3 belongs to the early B cell factor (EBF) family (also known as Olf, COE, or O/E) and is a transcription factor involved in neuronal differentiation and maturation.

MalaCards based summary : Hypotonia, Ataxia, and Delayed Development Syndrome, is also known as hadds. An important gene associated with Hypotonia, Ataxia, and Delayed Development Syndrome is EBF3 (EBF Transcription Factor 3). Affiliated tissues include eye, and related phenotypes are intellectual disability and dysarthria

OMIM® : 57 Hypotonia, ataxia, and delayed development syndrome (HADDS) is a neurodevelopmental syndrome characterized by congenital hypotonia, delayed psychomotor development, variable intellectual disability with speech delay, variable dysmorphic facial features, and ataxia, often associated with cerebellar hypoplasia. Some patients may have urogenital abnormalities (summary by Sleven et al., 2017). (617330) (Updated 20-May-2021)

UniProtKB/Swiss-Prot : 72 Hypotonia, ataxia, and delayed development syndrome: An autosomal dominant neurodevelopmental syndrome characterized by global developmental delay, moderate to severe intellectual disability, cerebellar ataxia, hypotonia, speech delay, variable dysmorphic features, and genitourinary abnormalities including vesicoureteric reflux.

Related Diseases for Hypotonia, Ataxia, and Delayed Development Syndrome

Symptoms & Phenotypes for Hypotonia, Ataxia, and Delayed Development Syndrome

Human phenotypes related to Hypotonia, Ataxia, and Delayed Development Syndrome:

31 (show top 50) (show all 64)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 very rare (1%) HP:0001249
2 dysarthria 31 very rare (1%) HP:0001260
3 dysphagia 31 very rare (1%) HP:0002015
4 global developmental delay 31 very rare (1%) HP:0001263
5 hypertelorism 31 very rare (1%) HP:0000316
6 delayed speech and language development 31 very rare (1%) HP:0000750
7 microcephaly 31 very rare (1%) HP:0000252
8 smooth philtrum 31 very rare (1%) HP:0000319
9 thick eyebrow 31 very rare (1%) HP:0000574
10 short stature 31 very rare (1%) HP:0004322
11 gastroesophageal reflux 31 very rare (1%) HP:0002020
12 stereotypy 31 very rare (1%) HP:0000733
13 prominent forehead 31 very rare (1%) HP:0011220
14 thick lower lip vermilion 31 very rare (1%) HP:0000179
15 strabismus 31 very rare (1%) HP:0000486
16 cryptorchidism 31 very rare (1%) HP:0000028
17 low-set ears 31 very rare (1%) HP:0000369
18 inverted nipples 31 very rare (1%) HP:0003186
19 dolichocephaly 31 very rare (1%) HP:0000268
20 downslanted palpebral fissures 31 very rare (1%) HP:0000494
21 upslanted palpebral fissure 31 very rare (1%) HP:0000582
22 downturned corners of mouth 31 very rare (1%) HP:0002714
23 micropenis 31 very rare (1%) HP:0000054
24 overfolded helix 31 very rare (1%) HP:0000396
25 vesicoureteral reflux 31 very rare (1%) HP:0000076
26 thin upper lip vermilion 31 very rare (1%) HP:0000219
27 long face 31 very rare (1%) HP:0000276
28 deeply set eye 31 very rare (1%) HP:0000490
29 deep philtrum 31 very rare (1%) HP:0002002
30 small earlobe 31 very rare (1%) HP:0000385
31 prominent nasal bridge 31 very rare (1%) HP:0000426
32 broad forehead 31 very rare (1%) HP:0000337
33 high forehead 31 very rare (1%) HP:0000348
34 dysmetria 31 very rare (1%) HP:0001310
35 decreased fetal movement 31 very rare (1%) HP:0001558
36 triangular face 31 very rare (1%) HP:0000325
37 synophrys 31 very rare (1%) HP:0000664
38 tapered finger 31 very rare (1%) HP:0001182
39 gait ataxia 31 very rare (1%) HP:0002066
40 broad-based gait 31 very rare (1%) HP:0002136
41 oligohydramnios 31 very rare (1%) HP:0001562
42 astigmatism 31 very rare (1%) HP:0000483
43 cerebellar atrophy 31 very rare (1%) HP:0001272
44 posteriorly rotated ears 31 very rare (1%) HP:0000358
45 thick upper lip vermilion 31 very rare (1%) HP:0000215
46 cerebellar vermis hypoplasia 31 very rare (1%) HP:0001320
47 broad nasal tip 31 very rare (1%) HP:0000455
48 generalized hypotonia 31 very rare (1%) HP:0001290
49 speech apraxia 31 very rare (1%) HP:0011098
50 pain insensitivity 31 very rare (1%) HP:0007021

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
intellectual disability
ataxia
dysarthria
global developmental delay
dysmetria
more
Head And Neck Eyes:
hypertelorism
strabismus
synophrys
astigmatism
downslanting palpebral fissures
more
Genitourinary External Genitalia Male:
cryptorchidism
micropenis
testicular failure

Chest Breasts:
inverted nipples

Head And Neck Nose:
broad nasal tip
high nasal bridge
short anteverted nostrils

Head And Neck Mouth:
thin upper lip
downturned corners of the mouth

Head And Neck Head:
microcephaly (in some patients)

Genitourinary External Genitalia Female:
hypoplasia of the labia majora

Abdomen Gastrointestinal:
dysphagia
gastroesophageal reflux

Head And Neck Face:
prominent forehead
long face
deep philtrum
triangular face
short chin
more
Head And Neck Ears:
low-set ears
posteriorly rotated ears
overfolded helices

Genitourinary Bladder:
vesicoureteral reflux

Muscle Soft Tissue:
hypotonia

Growth Height:
short stature (in some patients)

Neurologic Behavioral Psychiatric Manifestations:
stereotypic behaviors

Prenatal Manifestations Movement:
reduced fetal movements (in some patients)

Clinical features from OMIM®:

617330 (Updated 20-May-2021)

Drugs & Therapeutics for Hypotonia, Ataxia, and Delayed Development Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Deep High-Frequency Repetitive Transcranial Magnetic Stimulation for Smoking Cessation in Patients With Chronic Obstructive Pulmonary Disease (COPD) Completed NCT00951782 Phase 2, Phase 3
2 A Comparison of the Long Term Effects of the Traditional and Modified Posterior Shoulder Stretching Exercise on Shoulder Mobility, Pain, Ultrasonographic Parameters, Proprioception, Strength, Functionality, and Disability Level in Subacromial Impingement Syndrome Not yet recruiting NCT04660682

Search NIH Clinical Center for Hypotonia, Ataxia, and Delayed Development Syndrome

Genetic Tests for Hypotonia, Ataxia, and Delayed Development Syndrome

Genetic tests related to Hypotonia, Ataxia, and Delayed Development Syndrome:

# Genetic test Affiliating Genes
1 Hypotonia, Ataxia, and Delayed Development Syndrome 29 EBF3

Anatomical Context for Hypotonia, Ataxia, and Delayed Development Syndrome

MalaCards organs/tissues related to Hypotonia, Ataxia, and Delayed Development Syndrome:

40
Eye

Publications for Hypotonia, Ataxia, and Delayed Development Syndrome

Articles related to Hypotonia, Ataxia, and Delayed Development Syndrome:

# Title Authors PMID Year
1
De Novo Mutations in EBF3 Cause a Neurodevelopmental Syndrome. 6 57
28017370 2017
2
Mutations in EBF3 Disturb Transcriptional Profiles and Cause Intellectual Disability, Ataxia, and Facial Dysmorphism. 57 6
28017373 2017
3
A Syndromic Neurodevelopmental Disorder Caused by De Novo Variants in EBF3. 57 6
28017372 2017
4
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. 6
25741868 2015
5
Compliance with Canada's Fisheries Act: a field audit of habitat compensation projects. 61
16456632 2006
6
No net loss of fish habitat: a review and analysis of habitat compensation in Canada. 61
16082569 2005

Variations for Hypotonia, Ataxia, and Delayed Development Syndrome

ClinVar genetic disease variations for Hypotonia, Ataxia, and Delayed Development Syndrome:

6 (show all 28)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 EBF3 NM_001005463.3(EBF3):c.196A>G (p.Asn66Asp) SNV Pathogenic 375495 rs1057519518 GRCh37: 10:131761726-131761726
GRCh38: 10:129963462-129963462
2 EBF3 NM_001005463.3(EBF3):c.488G>A (p.Arg163Gln) SNV Pathogenic 268156 rs1057519389 GRCh37: 10:131755588-131755588
GRCh38: 10:129957324-129957324
3 EBF3 NM_001005463.3(EBF3):c.579G>T (p.Lys193Asn) SNV Pathogenic 375501 rs1057519520 GRCh37: 10:131676089-131676089
GRCh38: 10:129877825-129877825
4 EBF3 NM_001005463.3(EBF3):c.488G>T (p.Arg163Leu) SNV Pathogenic 268155 rs1057519389 GRCh37: 10:131755588-131755588
GRCh38: 10:129957324-129957324
5 EBF3 NM_001005463.3(EBF3):c.280_283del (p.Glu94fs) Deletion Pathogenic 375502 rs1057519521 GRCh37: 10:131761639-131761642
GRCh38: 10:129963375-129963378
6 EBF3 NM_001005463.3(EBF3):c.422A>G (p.Tyr141Cys) SNV Pathogenic 375497 rs1057519519 GRCh37: 10:131757261-131757261
GRCh38: 10:129958997-129958997
7 EBF3 NM_001005463.3(EBF3):c.625C>T (p.Arg209Trp) SNV Pathogenic 375494 rs779003155 GRCh37: 10:131676043-131676043
GRCh38: 10:129877779-129877779
8 EBF3 NM_001005463.3(EBF3):c.616C>T (p.Arg206Ter) SNV Pathogenic 375503 rs1057519522 GRCh37: 10:131676052-131676052
GRCh38: 10:129877788-129877788
9 EBF3 NM_001005463.3(EBF3):c.488G>C (p.Arg163Pro) SNV Pathogenic 375500 rs1057519389 GRCh37: 10:131755588-131755588
GRCh38: 10:129957324-129957324
10 EBF3 NM_001005463.3(EBF3):c.163G>T (p.Glu55Ter) SNV Pathogenic 692039 rs1589974634 GRCh37: 10:131761759-131761759
GRCh38: 10:129963495-129963495
11 EBF3 NM_001375380.1(EBF3):c.1128+1G>C SNV Pathogenic 802637 rs797046136 GRCh37: 10:131646655-131646655
GRCh38: 10:129848391-129848391
12 EBF3 NM_001375380.1(EBF3):c.636+1G>A SNV Pathogenic 828034 rs1589767274 GRCh37: 10:131676031-131676031
GRCh38: 10:129877767-129877767
13 EBF3 NM_001005463.3(EBF3):c.593G>A (p.Cys198Tyr) SNV Pathogenic 545444 rs1554904330 GRCh37: 10:131676075-131676075
GRCh38: 10:129877811-129877811
14 EBF3 NM_001375380.1(EBF3):c.481T>A (p.Cys161Ser) SNV Pathogenic 975542 GRCh37: 10:131757202-131757202
GRCh38: 10:129958938-129958938
15 EBF3 NM_001005463.3(EBF3):c.907C>T (p.Arg303Ter) SNV Pathogenic 423864 rs1064796669 GRCh37: 10:131665510-131665510
GRCh38: 10:129867246-129867246
16 EBF3 NM_001375380.1(EBF3):c.291+2del Deletion Pathogenic 1032516 GRCh37: 10:131761629-131761629
GRCh38: 10:129963365-129963365
17 EBF3 NM_001005463.3(EBF3):c.530C>T (p.Pro177Leu) SNV Pathogenic 224085 rs869312668 GRCh37: 10:131755546-131755546
GRCh38: 10:129957282-129957282
18 EBF3 NM_001375380.1(EBF3):c.412-2A>T SNV Likely pathogenic 993019 GRCh37: 10:131757273-131757273
GRCh38: 10:129959009-129959009
19 EBF3 NM_001375380.1(EBF3):c.1151C>T (p.Ala384Val) SNV Likely pathogenic 1029992 GRCh37: 10:131641444-131641444
GRCh38: 10:129843180-129843180
20 EBF3 NM_001375380.1(EBF3):c.656T>C (p.Val219Ala) SNV Likely pathogenic 976694 GRCh37: 10:131671841-131671841
GRCh38: 10:129873577-129873577
21 EBF3 NM_001005463.3(EBF3):c.461_462delinsCT (p.Leu154Pro) Indel Likely pathogenic 560684 rs1564927062 GRCh37: 10:131757221-131757222
GRCh38: 10:129958957-129958958
22 EBF3 NM_001375380.1(EBF3):c.428G>A (p.Gly143Asp) SNV Likely pathogenic 828142 rs1589962586 GRCh37: 10:131757255-131757255
GRCh38: 10:129958991-129958991
23 EBF3 NM_001005463.3(EBF3):c.554G>A (p.Arg185Lys) SNV Likely pathogenic 488452 rs1554934855 GRCh37: 10:131755522-131755522
GRCh38: 10:129957258-129957258
24 EBF3 NM_001375380.1(EBF3):c.1372+3A>G SNV Uncertain significance 1029993 GRCh37: 10:131640377-131640377
GRCh38: 10:129842113-129842113
25 EBF3 NM_001375380.1(EBF3):c.220C>T (p.Leu74Phe) SNV Uncertain significance 1032515 GRCh37: 10:131761702-131761702
GRCh38: 10:129963438-129963438
26 EBF3 NM_001005463.3(EBF3):c.487C>T (p.Arg163Trp) SNV Uncertain significance 374797 rs1057519092 GRCh37: 10:131755589-131755589
GRCh38: 10:129957325-129957325
27 EBF3 NM_001375380.1(EBF3):c.82C>A (p.Arg28Ser) SNV Uncertain significance 1032517 GRCh37: 10:131761951-131761951
GRCh38: 10:129963687-129963687
28 EBF3 NM_001005463.3(EBF3):c.806del (p.Gly269fs) Deletion not provided 684472 rs1589745620 GRCh37: 10:131666125-131666125
GRCh38: 10:129867861-129867861

UniProtKB/Swiss-Prot genetic disease variations for Hypotonia, Ataxia, and Delayed Development Syndrome:

72
# Symbol AA change Variation ID SNP ID
1 EBF3 p.Asn66Asp VAR_078033 rs105751951
2 EBF3 p.Tyr141Cys VAR_078034 rs105751951
3 EBF3 p.Arg163Leu VAR_078036 rs105751938
4 EBF3 p.Arg163Pro VAR_078037 rs105751938
5 EBF3 p.Arg163Gln VAR_078038 rs105751938
6 EBF3 p.Gly171Asp VAR_078039 rs105751943
7 EBF3 p.Pro177Leu VAR_078040 rs869312668
8 EBF3 p.Lys193Asn VAR_078041 rs105751952
9 EBF3 p.Arg209Trp VAR_078042 rs779003155

Expression for Hypotonia, Ataxia, and Delayed Development Syndrome

Search GEO for disease gene expression data for Hypotonia, Ataxia, and Delayed Development Syndrome.

Pathways for Hypotonia, Ataxia, and Delayed Development Syndrome

GO Terms for Hypotonia, Ataxia, and Delayed Development Syndrome

Sources for Hypotonia, Ataxia, and Delayed Development Syndrome

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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