MCID: ALL001
MIFTS: 49

Allan-Herndon-Dudley Syndrome

Categories: Genetic diseases, Rare diseases

Aliases & Classifications for Allan-Herndon-Dudley Syndrome

MalaCards integrated aliases for Allan-Herndon-Dudley Syndrome:

Name: Allan-Herndon-Dudley Syndrome 53 12 49 24 71 36 28 13 14 69
Allan-Herndon Syndrome 53 12 49 24
Ahds 53 49 71
Mental Retardation, X-Linked, with Hypotonia 53 24
Monocarboxylate Transporter 8 Deficiency 53 71
Mct8 -Specific Thyroid Hormone Cell Transporter Deficiency 24
X-Linked Intellectual Disability with Hypotonia 49
Intellectual Disability and Muscular Atrophy 49
Monocarboxylate Transporter 8 Deficiency 24
Monocarboxylate Transporter-8 Deficiency 49
Mental Retardation and Muscular Atrophy 53
Triiodothyronine Resistance 53
Triiodothyronine Resistence 49
Mct8 Deficiency 71
T3 Resisitence 49
T3 Resistance 53

Characteristics:

OMIM:

53
Miscellaneous:
onset at birth
heterozygous females may have milder thyroid phenotype and no neurologic abnormalities
no peripheral signs of hypothyroidism

Inheritance:
x-linked


HPO:

31
allan-herndon-dudley syndrome:
Onset and clinical course congenital onset
Inheritance x-linked dominant inheritance


Classifications:



Summaries for Allan-Herndon-Dudley Syndrome

UniProtKB/Swiss-Prot : 71 Monocarboxylate transporter 8 deficiency: Consists of a severe form of X-linked psychomotor retardation combined with abnormal thyroid hormone (TH) levels. Thyroid hormone deficiency can be caused by defects of hormone synthesis and action, but it has also been linked to a defect in cellular hormone transport. Affected patients are males with abnormal relative concentrations of three circulating iodothyronines, as well as severe neurological abnormalities, including global developmental delay, central hypotonia, spastic quadriplegia, dystonic movements, rotary nystagmus, and impaired gaze and hearing. Heterozygous females had a milder thyroid phenotype and no neurological defects.

MalaCards based summary : Allan-Herndon-Dudley Syndrome, also known as allan-herndon syndrome, is related to mct8-specific thyroid hormone cell-membrane transporter deficiency and pelizaeus-merzbacher-like disease, and has symptoms including ataxia, joint stiffness and athetosis. An important gene associated with Allan-Herndon-Dudley Syndrome is SLC16A2 (Solute Carrier Family 16 Member 2), and among its related pathways/superpathways are Blood-Brain Barrier and Immune Cell Transmigration: Pathways Overview and Thyroid hormone signaling pathway. The drugs Ephedrine and Guaifenesin have been mentioned in the context of this disorder. Affiliated tissues include thyroid, brain and eye.

Disease Ontology : 12 An X-linked disease that has material basis in mutation at is in the gene encoding the monocarboxylate transporter-8 which alters the structure and function of the SLC16A2 protein which is then unable to transport the thyroid triiodothyronine (T3) hormone into nerve cells of the developing brain affecting normal brain development resulting in intellectual disability and problems with movement.

Genetics Home Reference : 24 Allan-Herndon-Dudley syndrome is a rare disorder of brain development that causes moderate to severe intellectual disability and problems with movement. This condition, which occurs exclusively in males, disrupts development from before birth. Although affected males have impaired speech and a limited ability to communicate, they seem to enjoy interaction with other people.

NIH Rare Diseases : 49 Allan-Herndon-Dudley syndrome is a disorder of brain development that causes moderate to severe intellectual disability and problems with movement. This condition, which occurs exclusively in males, disrupts development from before birth. Although affected males have speech and a limited ability to communicate, they seem to enjoy interaction with others. Allan-Herndon-Dudley syndrome is caused by mutations in the SLC16A2 gene. It is inherited in an X-linked recessive manner.  Last updated: 6/12/2014

Description from OMIM: 300523

Related Diseases for Allan-Herndon-Dudley Syndrome

Diseases related to Allan-Herndon-Dudley Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 11)
# Related Disease Score Top Affiliating Genes
1 mct8-specific thyroid hormone cell-membrane transporter deficiency 11.7
2 pelizaeus-merzbacher-like disease 11.5
3 alagille syndrome 1 11.1
4 alveolar echinococcosis 11.0
5 thyroiditis 10.5
6 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.4
7 hereditary spastic paraplegia 10.4
8 sensorineural hearing loss 10.4
9 paraplegia 10.4
10 neuronitis 10.4
11 spasticity 10.4

Graphical network of the top 20 diseases related to Allan-Herndon-Dudley Syndrome:



Diseases related to Allan-Herndon-Dudley Syndrome

Symptoms & Phenotypes for Allan-Herndon-Dudley Syndrome

Symptoms via clinical synopsis from OMIM:

53
NeurologicCentralNervousSystem:
ataxia
clonus
dysarthria
hyperreflexia
neonatal hypotonia
more
HeadAndNeckHead:
microcephaly

SkeletalFeet:
flat feet
lateral deviation of great toe

HeadAndNeckFace:
bitemporal narrowing
elongated face

HeadAndNeckEyes:
disconjugate eye movements
nystagmus, rotary (in some patients)

Skeletal:
joint contractures (small and large joints affected)

SkeletalSpine:
scoliosis

NeurologicBehavioralPsychiatricManifestations:
irritability

HeadAndNeckEars:
large ears
simple ears
prominent antihelix
pinna modeling anomalies
flattened antihelix

AbdomenGastrointestinal:
poor feeding

ChestRibsSternumClaviclesAndScapulae:
pectus excavatum, broad, shallow

LaboratoryAbnormalities:
decreased serum thyroxine (t4)
decreased serum free thyroxine
normal or mildly increased thyroid-stimulating hormone (tsh)
increased serum triiodothyronine (t3)
decreased serum rt3


Clinical features from OMIM:

300523

Human phenotypes related to Allan-Herndon-Dudley Syndrome:

31 (show top 50) (show all 54)
# Description HPO Frequency HPO Source Accession
1 ataxia 31 hallmark (90%) HP:0001251
2 joint stiffness 31 frequent (33%) HP:0001387
3 athetosis 31 HP:0002305
4 clonus 31 HP:0002169
5 pectus excavatum 31 HP:0000767
6 ptosis 31 occasional (7.5%) HP:0000508
7 hypothyroidism 31 HP:0000821
8 dysarthria 31 HP:0001260
9 hyperreflexia 31 hallmark (90%) HP:0001347
10 cerebral calcification 31 occasional (7.5%) HP:0002514
11 bowel incontinence 31 hallmark (90%) HP:0002607
12 scoliosis 31 occasional (7.5%) HP:0002650
13 macrotia 31 frequent (33%) HP:0000400
14 pes planus 31 HP:0001763
15 microcephaly 31 HP:0000252
16 neonatal hypotonia 31 HP:0001319
17 flexion contracture 31 HP:0001371
18 feeding difficulties in infancy 31 HP:0008872
19 type i diabetes mellitus 31 occasional (7.5%) HP:0100651
20 spastic tetraplegia 31 HP:0002510
21 intellectual disability, severe 31 hallmark (90%) HP:0010864
22 skeletal muscle atrophy 31 hallmark (90%) HP:0003202
23 irritability 31 HP:0000737
24 severe global developmental delay 31 hallmark (90%) HP:0011344
25 absent speech 31 hallmark (90%) HP:0001344
26 biparietal narrowing 31 hallmark (90%) HP:0004422
27 babinski sign 31 HP:0003487
28 inability to walk 31 hallmark (90%) HP:0002540
29 protruding ear 31 occasional (7.5%) HP:0000411
30 aphasia 31 hallmark (90%) HP:0002381
31 intellectual disability, progressive 31 hallmark (90%) HP:0006887
32 narrow face 31 hallmark (90%) HP:0000275
33 open mouth 31 frequent (33%) HP:0000194
34 upslanted palpebral fissure 31 hallmark (90%) HP:0000582
35 bilateral single transverse palmar creases 31 frequent (33%) HP:0007598
36 abnormality of the neck 31 hallmark (90%) HP:0000464
37 hallux valgus 31 HP:0001822
38 proptosis 31 occasional (7.5%) HP:0000520
39 spastic paraplegia 31 HP:0001258
40 camptodactyly of finger 31 occasional (7.5%) HP:0100490
41 leukodystrophy 31 HP:0002415
42 drooling 31 HP:0002307
43 generalized amyotrophy 31 HP:0003700
44 urinary incontinence 31 hallmark (90%) HP:0000020
45 hypoplasia of the musculature 31 hallmark (90%) HP:0009004
46 narrow forehead 31 HP:0000341
47 delayed cns myelination 31 HP:0002188
48 abnormal conjugate eye movement 31 HP:0000549
49 prominent antihelix 31 HP:0000395
50 rotary nystagmus 31 occasional (7.5%) HP:0001583

UMLS symptoms related to Allan-Herndon-Dudley Syndrome:


clonus, ataxia

Drugs & Therapeutics for Allan-Herndon-Dudley Syndrome

Drugs for Allan-Herndon-Dudley Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 18)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Ephedrine Approved Phase 2 299-42-3 9294
2
Guaifenesin Approved, Investigational, Vet_approved Phase 2 93-14-1 3516
3
Pseudoephedrine Approved Phase 2 90-82-4 7028
4 Adrenergic Agents Phase 2
5 Adrenergic Agonists Phase 2
6 Adrenergic alpha-Agonists Phase 2
7 Anti-Obesity Agents Phase 2
8 Appetite Depressants Phase 2
9 Autonomic Agents Phase 2
10
Chlorpheniramine Phase 2 113-92-8, 132-22-9 2725
11 Chlorpheniramine, phenylpropanolamine drug combination Phase 2
12 Expectorants Phase 2
13 Hormones Phase 2
14 Nasal Decongestants Phase 2
15 Neurotransmitter Agents Phase 2
16 Peripheral Nervous System Agents Phase 2
17 Respiratory System Agents Phase 2
18 Vasoconstrictor Agents Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Triac Trial in MCT8 Patients Active, not recruiting NCT02060474 Phase 2 Triac
2 Triac Trial II in MCT8 Patients Not yet recruiting NCT02396459 Phase 2 Triac

Search NIH Clinical Center for Allan-Herndon-Dudley Syndrome

Genetic Tests for Allan-Herndon-Dudley Syndrome

Genetic tests related to Allan-Herndon-Dudley Syndrome:

# Genetic test Affiliating Genes
1 Allan-Herndon-Dudley Syndrome 28 SLC16A2

Anatomical Context for Allan-Herndon-Dudley Syndrome

MalaCards organs/tissues related to Allan-Herndon-Dudley Syndrome:

38
Thyroid, Brain, Eye, Bone, Skeletal Muscle

Publications for Allan-Herndon-Dudley Syndrome

Articles related to Allan-Herndon-Dudley Syndrome:

(show all 27)
# Title Authors Year
1
Erratum: Correction: Novel SLC16A2 mutations in patients with Allan-Herndon-Dudley syndrome. ( 28944150 )
2017
2
A novel A178P mutation in SLC16A2 in a patient with Allan-Herndon-Dudley syndrome. ( 28862359 )
2017
3
The Chemical Chaperone Phenylbutyrate Rescues MCT8 Mutations Associated With Milder Phenotypes in Patients With Allan-Herndon-Dudley Syndrome. ( 27977298 )
2017
4
Clinical and Molecular Characteristics of SLC16A2 (MCT8) Mutations in Three Families with the Allan-Herndon-Dudley Syndrome. ( 27805744 )
2016
5
Novel SLC16A2 mutations in patients with Allan-Herndon-Dudley syndrome. ( 27672545 )
2016
6
Allan-Herndon-Dudley syndrome with unusual profound sensorineural hearing loss. ( 25850411 )
2015
7
Further Insights into the Allan-Herndon-Dudley Syndrome: Clinical and Functional Characterization of a Novel MCT8 Mutation. ( 26426690 )
2015
8
Deletion of exon 1 of the SLC16A2 gene: a common occurrence in patients with Allan-Herndon-Dudley syndrome. ( 25517855 )
2015
9
Clinical and Endocrine Features of Two Allan-Herndon-Dudley Syndrome Patients with Monocarboxylate Transporter 8 Mutations. ( 25896225 )
2015
10
Comment on "Delayed myelination is not a constant feature of Allan-Herndon-Dudley syndrome: Report of a new case and review of the literature" by Azzolini S et al. Brain & Development 2014;36:716-720. ( 25863745 )
2015
11
A 7-month-old male with Allan-Herndon-Dudley syndrome and the power of T3. ( 25755011 )
2015
12
SLC16A2 mutations in two Japanese patients with Allan-Herndon-Dudley syndrome. ( 27081503 )
2014
13
Myelination Delay and Allan-Herndon-Dudley Syndrome Caused by a Novel Mutation in the SLC16A2 Gene. ( 25380603 )
2014
14
Clinical course and images of four familial cases of Allan-Herndon-Dudley syndrome with a novel monocarboxylate transporter 8 gene mutation. ( 25160547 )
2014
15
Mutations in MCT8 in patients with Allan-Herndon-Dudley-syndrome affecting its cellular distribution. ( 23550058 )
2013
16
Delayed myelination is not a constant feature of Allan-Herndon-Dudley syndrome: Report of a new case and review of the literature. ( 24268987 )
2013
17
Allan-Herndon-Dudley syndrome (AHDS) in two consecutive generations caused by a missense MCT8 gene mutation. Phenotypic variability with the presence of normal serum T3 levels. ( 23419639 )
2013
18
A Novel Deletion Mutation of SLC16A2 Encoding Monocarboxylate Transporter (MCT) 8 in a 26-year-old Japanese Patient with Allan-Herndon-Dudley Syndrome. ( 24170966 )
2013
19
Allan-Herndon-Dudley syndrome (AHDS) caused by a novel SLC16A2 gene mutation showing severe neurologic features and unexpectedly low TRH-stimulated serum TSH. ( 20713192 )
2010
20
Neuronal 3',3,5-triiodothyronine (T3) uptake and behavioral phenotype of mice deficient in Mct8, the neuronal T3 transporter mutated in Allan-Herndon-Dudley syndrome. ( 19641107 )
2009
21
Allan-Herndon-Dudley syndrome. ( 18589880 )
2008
22
MCT8 mutation analysis and identification of the first female with Allan-Herndon-Dudley syndrome due to loss of MCT8 expression. ( 18398436 )
2008
23
The MCT8 thyroid hormone transporter and Allan-Herndon-Dudley syndrome. ( 17574010 )
2007
24
Decreased cellular uptake and metabolism in Allan-Herndon-Dudley syndrome (AHDS) due to a novel mutation in the MCT8 thyroid hormone transporter. ( 15980113 )
2006
25
Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene. ( 15889350 )
2005
26
Allan-Herndon-Dudley syndrome: should the locus for this hereditary spastic paraplegia be designated SPG 22? ( 15364700 )
2004
27
Allan-Herndon-Dudley syndrome: clinical and linkage studies on a second family. ( 1605231 )
1992

Variations for Allan-Herndon-Dudley Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Allan-Herndon-Dudley Syndrome:

71 (show all 20)
# Symbol AA change Variation ID SNP ID
1 SLC16A2 p.Ala150Val VAR_022348 rs104894936
2 SLC16A2 p.Leu397Pro VAR_022349 rs122455132
3 SLC16A2 p.Leu438Pro VAR_022350 rs104894931
4 SLC16A2 p.Ser120Phe VAR_059054 rs113994162
5 SLC16A2 p.Val161Met VAR_059056
6 SLC16A2 p.Leu360Trp VAR_059057 rs104894939
7 SLC16A2 p.Gly490Arg VAR_059059 rs794727799
8 SLC16A2 p.Leu494Pro VAR_059060 rs104894938
9 SLC16A2 p.Gly147Arg VAR_074572
10 SLC16A2 p.Ala150Thr VAR_074573 rs373279555
11 SLC16A2 p.Arg197His VAR_074574 rs727504155
12 SLC16A2 p.Gly208Cys VAR_074575
13 SLC16A2 p.Pro247Leu VAR_074576
14 SLC16A2 p.Arg371Cys VAR_074577 rs587784384
15 SLC16A2 p.Asp379Val VAR_074578
16 SLC16A2 p.Pro463Leu VAR_074579
17 SLC16A2 p.Gly484Asp VAR_074580
18 SLC16A2 p.Ser216Phe VAR_075145 rs398124232
19 SLC16A2 p.Leu217Arg VAR_078497
20 SLC16A2 p.Gly490Glu VAR_078498

ClinVar genetic disease variations for Allan-Herndon-Dudley Syndrome:

6 (show all 29)
# Gene Variation Type Significance SNP ID Assembly Location
1 SLC16A2 NM_006517.4(SLC16A2): c.1313T> C (p.Leu438Pro) single nucleotide variant Pathogenic rs104894931 GRCh37 Chromosome X, 73749190: 73749190
2 SLC16A2 SLC16A2, 1-BP DEL, 1212T deletion Pathogenic
3 SLC16A2 NM_006517.4(SLC16A2): c.449C> T (p.Ala150Val) single nucleotide variant Pathogenic rs104894936 GRCh37 Chromosome X, 73740843: 73740843
4 SLC16A2 SLC16A2, EX1DEL deletion Pathogenic
5 SLC16A2 NM_006517.4(SLC16A2): c.1190T> C (p.Leu397Pro) single nucleotide variant Pathogenic rs122455132 GRCh37 Chromosome X, 73749067: 73749067
6 SLC16A2 nsv513796 deletion Pathogenic
7 SLC16A2 NM_006517.4(SLC16A2): c.1481T> C (p.Leu494Pro) single nucleotide variant Pathogenic rs104894938 GRCh37 Chromosome X, 73751249: 73751249
8 SLC16A2 NM_006517.4(SLC16A2): c.1079T> G (p.Leu360Trp) single nucleotide variant Pathogenic rs104894939 GRCh37 Chromosome X, 73745637: 73745637
9 SLC16A2 NM_006517.4(SLC16A2): c.1121C> A (p.Ser374Ter) single nucleotide variant Pathogenic rs104894940 GRCh37 Chromosome X, 73745679: 73745679
10 SLC16A2 NM_006517.4(SLC16A2): c.461_463delTCT (p.Phe156del) deletion Pathogenic/Likely pathogenic rs387906501 GRCh38 Chromosome X, 74521026: 74521028
11 SLC16A2 NM_006517.4(SLC16A2): c.1612delC (p.Pro538Glnfs) deletion Pathogenic rs113994166 GRCh37 Chromosome X, 73751380: 73751380
12 SLC16A2 NM_006517.4(SLC16A2): c.1278_1280delCTT (p.Phe427del) deletion Pathogenic rs113994164 GRCh37 Chromosome X, 73749155: 73749157
13 SLC16A2 NM_006517.4(SLC16A2): c.359C> T (p.Ser120Phe) single nucleotide variant Pathogenic rs113994162 GRCh37 Chromosome X, 73641831: 73641831
14 SLC16A2 NM_006517.4(SLC16A2): c.1253T> C (p.Leu418Pro) single nucleotide variant Pathogenic rs367543059 GRCh37 Chromosome X, 73749130: 73749130
15 SLC16A2 NM_006517.4(SLC16A2): c.916C> T (p.Gln306Ter) single nucleotide variant Pathogenic rs587784382 GRCh37 Chromosome X, 73744534: 73744534
16 SLC16A2 NM_006517.4(SLC16A2): c.277C> T (p.Gln93Ter) single nucleotide variant Pathogenic rs587784386 GRCh37 Chromosome X, 73641749: 73641749
17 SLC16A2 NM_006517.4(SLC16A2): c.449C> A (p.Ala150Glu) single nucleotide variant Likely pathogenic rs104894936 GRCh37 Chromosome X, 73740843: 73740843
18 SLC16A2 NM_006517.4(SLC16A2): c.979G> A (p.Gly327Arg) single nucleotide variant Likely pathogenic rs587784383 GRCh37 Chromosome X, 73744597: 73744597
19 SLC16A2 NM_006517.4(SLC16A2): c.1111C> T (p.Arg371Cys) single nucleotide variant Pathogenic/Likely pathogenic rs587784384 GRCh37 Chromosome X, 73745669: 73745669
20 SLC16A2 NM_006517.4(SLC16A2): c.326G> A (p.Trp109Ter) single nucleotide variant Pathogenic rs794726932 GRCh37 Chromosome X, 73641798: 73641798
21 SLC16A2 NM_006517.4(SLC16A2): c.353A> C (p.His118Pro) single nucleotide variant Likely pathogenic rs794726933 GRCh37 Chromosome X, 73641825: 73641825
22 SLC16A2 NM_006517.4(SLC16A2): c.256delC (p.Arg86Alafs) deletion Pathogenic rs797045965 GRCh37 Chromosome X, 73641728: 73641728
23 SLC16A2 NM_006517.4(SLC16A2): c.374delA (p.Tyr125Serfs) deletion Pathogenic rs797045966 GRCh37 Chromosome X, 73641846: 73641846
24 SLC16A2 NM_006517.4(SLC16A2): c.940C> T (p.Arg314Ter) single nucleotide variant Pathogenic rs766773277 GRCh38 Chromosome X, 74524723: 74524723
25 SLC16A2 NM_006517.4(SLC16A2): c.1392dupC (p.Ile465Hisfs) duplication Pathogenic rs797045962 GRCh38 Chromosome X, 74529434: 74529434
26 SLC16A2 NM_006517.4(SLC16A2): c.1474_1481delGTAATCCT (p.Val492Leufs) deletion Pathogenic rs797045963 GRCh37 Chromosome X, 73751242: 73751249
27 SLC16A2 NM_006517.4(SLC16A2): c.576-1G> A single nucleotide variant Pathogenic rs886042238 GRCh37 Chromosome X, 73744193: 73744193
28 SLC16A2 NM_006517.4(SLC16A2): c.532delG (p.Ala178Leufs) deletion Pathogenic GRCh38 Chromosome X, 74521091: 74521091
29 SLC16A2 NM_006517.4(SLC16A2): c.1026+1G> T single nucleotide variant Pathogenic GRCh38 Chromosome X, 74524810: 74524810

Expression for Allan-Herndon-Dudley Syndrome

Search GEO for disease gene expression data for Allan-Herndon-Dudley Syndrome.

Pathways for Allan-Herndon-Dudley Syndrome

GO Terms for Allan-Herndon-Dudley Syndrome

Biological processes related to Allan-Herndon-Dudley Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 sodium-independent organic anion transport GO:0043252 8.96 SLC16A2 SLCO1C1
2 thyroid hormone transport GO:0070327 8.62 SLC16A2 SLCO1C1

Molecular functions related to Allan-Herndon-Dudley Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 thyroid hormone transmembrane transporter activity GO:0015349 8.62 SLC16A2 SLCO1C1

Sources for Allan-Herndon-Dudley Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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