MCID: ALP014
MIFTS: 53

Alpha-Thalassemia/mental Retardation Syndrome malady

Genetic diseases, Neuronal diseases, Reproductive diseases, Endocrine diseases, Fetal diseases, Blood diseases, Rare diseases, Mental diseases categories
Download this MalaCard

Summaries for Alpha-Thalassemia/mental Retardation Syndrome

About this section


Fully expand this MalaCard
Genetics Home Reference:21 Alpha thalassemia X-linked intellectual disability syndrome is an inherited disorder that affects many parts of the body. This condition occurs almost exclusively in males.

MalaCards based summary: Alpha-Thalassemia/mental Retardation Syndrome, also known as atr-x syndrome, is related to mental retardation and thalassemia, and has symptoms including microcephaly, large fontanelle/delayed fontanelle closure and face/facial anomalies. An important gene associated with Alpha-Thalassemia/mental Retardation Syndrome is ATRX (alpha thalassemia/mental retardation syndrome X-linked), and among its related pathways are Post NMDA receptor activation events and Transcription CREB pathway. The compounds p003 and hpaii have been mentioned in the context of this disorder. Affiliated tissues include eye, testes and colon, and related mouse phenotypes are adipose tissue and no phenotypic analysis.

Wikipedia:65 Alpha-thalassemia mental retardation syndrome (ATRX), also called alpha-thalassemia X-linked mental... more...

Description from OMIM:46 301040

Aliases & Classifications for Alpha-Thalassemia/mental Retardation Syndrome

About this section
Sources:
48Orphanet, 62UMLS, 46OMIM, 26ICD10 via Orphanet, 63UMLS via Orphanet
See all sources

Alpha-Thalassemia/mental Retardation Syndrome, Aliases & Descriptions:

Name: Alpha-Thalassemia/mental Retardation Syndrome 46
Atr-X Syndrome 48 62
 
Alpha-Thalassemia - X-Linked Intellectual Disability Syndrome 48
Alpha Thalassaemia-Mental Retardation Syndrome 62


Classifications:



Characteristics (Orphanet epidemiological data):

48
atr-x syndrome:
Inheritance: X-linked recessive; Age of onset: Neonatal/infancy


External Ids:

OMIM46 301040
ICD10 via Orphanet26 D56.0
UMLS via Orphanet63 C1845055

Related Diseases for Alpha-Thalassemia/mental Retardation Syndrome

About this section

Graphical network of diseases related to Alpha-Thalassemia/mental Retardation Syndrome:



Diseases related to alpha-thalassemia/mental retardation syndrome

Symptoms for Alpha-Thalassemia/mental Retardation Syndrome

About this section

Symptoms by clinical synopsis from OMIM:

301040

Clinical features from OMIM:

301040

Symptoms:

48 (show all 55)
  • microcephaly
  • large fontanelle/delayed fontanelle closure
  • face/facial anomalies
  • flat face
  • hypertelorism
  • gastroesophageal reflux/pyrosis/esophagitis/hiatal hernia/gastroparesia
  • structural anomalies of the genital system
  • ambiguous genitalia
  • male pseudohermaphrodism/lack of virilisation
  • undescended/ectopic testes/cryptorchidia/unfixed testes
  • speech troubles/aphasia/dysphasia/echolalia/mutism/logorrhea/dysprosodia
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • psychic/behavioural troubles
  • x-linked recessive inheritance
  • mid-facial hypoplasia/short/small midface
  • epicanthic folds
  • telecanthus/canthal dystopy
  • flattened nose
  • anteverted nares/nostrils
  • thick lips
  • everted lower lip
  • macroglossia/tongue protrusion/proeminent/hypertrophic
  • talipes-varus/metatarsal varus
  • micropenis/small penis/agenesis
  • hypotonia
  • seizures/epilepsy/absences/spasms/status epilepticus
  • autism/autistic disoders
  • hemoglobinosis/hemoglobinopathy
  • short stature/dwarfism/nanism
  • optic nerve anomaly/optic atrophy/anomaly of the papilla
  • visual loss/blindness/amblyopia
  • myopia
  • anomalies of teeth and dentition
  • sensorineural deafness/hearing loss
  • short hand/brachydactyly
  • clinodactyly of fifth finger
  • dolichocolon/megacolon/megadolichocolon/hirschsprung's disease
  • colonic/intestinal volvulus
  • feeding disorder/dysphagia/swallowing/sucking disorder/esophageal dyskinesia
  • nausea/vomiting/regurgitation/merycism/hyperemesis
  • constipation
  • renal/kidney anomalies
  • megaureter/hydronephrosis/pyeloureteral junction syndrome
  • recurrent urinary infections
  • cortical atrophy without hydrocephaly/cerebral hemiatrophy/subcortical atrophy
  • corpus callosum/septum pellucidum total/partial agenesis
  • encephalitis
  • movement disorder
  • hemiplegia/diplegia/hemiparesia/limb palsy
  • humour troubles/anxiety/depression/apathy/euphoria/irritability
  • auto-aggressivity/auto-mutilation
  • contractures/cramps/trismus/tetania/claudication/opisthotonos
  • restricted joint mobility/joint stiffness/ankylosis
  • anaemia
  • death in infancy

HPO human phenotypes related to Alpha-Thalassemia/mental Retardation Syndrome:

(show all 93)
id Description Frequency HPO Source Accession
1 cryptorchidism hallmark (90%) HP:0000028
2 male pseudohermaphroditism hallmark (90%) HP:0000037
3 ambiguous genitalia hallmark (90%) HP:0000062
4 abnormality of the fontanelles or cranial sutures hallmark (90%) HP:0000235
5 microcephaly hallmark (90%) HP:0000252
6 malar flattening hallmark (90%) HP:0000272
7 hypertelorism hallmark (90%) HP:0000316
8 neurological speech impairment hallmark (90%) HP:0002167
9 cognitive impairment hallmark (90%) HP:0100543
10 abnormality of the tongue typical (50%) HP:0000157
11 thick lower lip vermilion typical (50%) HP:0000179
12 everted lower lip vermilion typical (50%) HP:0000232
13 malar flattening typical (50%) HP:0000272
14 epicanthus typical (50%) HP:0000286
15 depressed nasal ridge typical (50%) HP:0000457
16 anteverted nares typical (50%) HP:0000463
17 telecanthus typical (50%) HP:0000506
18 autism typical (50%) HP:0000717
19 seizures typical (50%) HP:0001250
20 muscular hypotonia typical (50%) HP:0001252
21 talipes typical (50%) HP:0001883
22 short stature typical (50%) HP:0004322
23 hypoplasia of penis typical (50%) HP:0008736
24 abnormality of the heme biosynthetic pathway typical (50%) HP:0010472
25 seizures frequent (33%) HP:0001250
26 recurrent urinary tract infections occasional (7.5%) HP:0000010
27 abnormality of the kidney occasional (7.5%) HP:0000077
28 abnormality of the teeth occasional (7.5%) HP:0000164
29 sensorineural hearing impairment occasional (7.5%) HP:0000407
30 visual impairment occasional (7.5%) HP:0000505
31 myopia occasional (7.5%) HP:0000545
32 optic atrophy occasional (7.5%) HP:0000648
33 brachydactyly syndrome occasional (7.5%) HP:0001156
34 flexion contracture occasional (7.5%) HP:0001371
35 limitation of joint mobility occasional (7.5%) HP:0001376
36 anemia occasional (7.5%) HP:0001903
37 nausea and vomiting occasional (7.5%) HP:0002017
38 constipation occasional (7.5%) HP:0002019
39 cerebral cortical atrophy occasional (7.5%) HP:0002120
40 aganglionic megacolon occasional (7.5%) HP:0002251
41 encephalitis occasional (7.5%) HP:0002383
42 volvulus occasional (7.5%) HP:0002580
43 clinodactyly of the 5th finger occasional (7.5%) HP:0004209
44 hemiplegia/hemiparesis occasional (7.5%) HP:0004374
45 aplasia/hypoplasia of the corpus callosum occasional (7.5%) HP:0007370
46 feeding difficulties in infancy occasional (7.5%) HP:0008872
47 abnormality of movement occasional (7.5%) HP:0100022
48 self-injurious behavior occasional (7.5%) HP:0100716
49 cryptorchidism HP:0000028
50 hypospadias HP:0000047
51 shawl scrotum HP:0000049
52 micropenis HP:0000054
53 renal agenesis HP:0000104
54 hydronephrosis HP:0000126
55 macroglossia HP:0000158
56 thick lower lip vermilion HP:0000179
57 microcephaly HP:0000252
58 malar flattening HP:0000272
59 epicanthus HP:0000286
60 hypertelorism HP:0000316
61 posteriorly rotated ears HP:0000358
62 low-set ears HP:0000369
63 sensorineural hearing impairment HP:0000407
64 anteverted nares HP:0000463
65 tapered finger HP:0001182
66 intellectual disability HP:0001249
67 spasticity HP:0001257
68 global developmental delay HP:0001263
69 x-linked dominant inheritance HP:0001423
70 umbilical hernia HP:0001537
71 widely-spaced maxillary central incisors HP:0001566
72 talipes equinovarus HP:0001762
73 abnormality of metabolism/homeostasis HP:0001939
74 constipation HP:0002019
75 gastroesophageal reflux HP:0002020
76 cerebral atrophy HP:0002059
77 coxa valga HP:0002673
78 absent frontal sinuses HP:0002688
79 kyphoscoliosis HP:0002751
80 hemivertebrae HP:0002937
81 short nose HP:0003196
82 phenotypic variability HP:0003812
83 hypochromic microcytic anemia HP:0004840
84 depressed nasal bridge HP:0005280
85 microtia HP:0008551
86 postnatal growth retardation HP:0008897
87 infantile muscular hypotonia HP:0008947
88 radial deviation of finger HP:0009466
89 u-shaped upper lip vermilion HP:0010806
90 protruding tongue HP:0010808
91 perimembranous ventricular septal defect HP:0011682
92 reduced alpha/beta synthesis ratio HP:0011907
93 clinodactyly HP:0030084

Drugs & Therapeutics for Alpha-Thalassemia/mental Retardation Syndrome

About this section

Drug clinical trials:

Search ClinicalTrials for Alpha-Thalassemia/mental Retardation Syndrome

Search NIH Clinical Center for Alpha-Thalassemia/mental Retardation Syndrome

Genetic Tests for Alpha-Thalassemia/mental Retardation Syndrome

About this section

Anatomical Context for Alpha-Thalassemia/mental Retardation Syndrome

About this section

MalaCards organs/tissues related to Alpha-Thalassemia/mental Retardation Syndrome:

32
Eye, Testes, Colon, Kidney, Tongue

Animal Models for Alpha-Thalassemia/mental Retardation Syndrome or affiliated genes

About this section

MGI Mouse Phenotypes related to Alpha-Thalassemia/mental Retardation Syndrome:

36
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053758.9CREBBP, RPS6KA3, MECP2
2MP:00030128.4NSD1, MECP2, RPS6KA3, WT1
3MP:00053898.4ATRX, MECP2, RPS6KA3, WT1
4MP:00053888.3MECP2, RPS6KA3, CREBBP, WT1
5MP:00053858.2WT1, CREBBP, RPS6KA3, ATRX
6MP:00053798.2MECP2, RPS6KA3, CREBBP, WT1
7MP:00053787.9WT1, CREBBP, RPS6KA3, MECP2, ATRX
8MP:00053807.9WT1, CREBBP, MECP2, NSD1, ATRX
9MP:00107687.4ATRX, NSD1, MECP2, CREBBP, WT1

Publications for Alpha-Thalassemia/mental Retardation Syndrome

About this section

Articles related to Alpha-Thalassemia/mental Retardation Syndrome:

(show all 20)
idTitleAuthorsYear
1
Alpha thalassemia/mental retardation syndrome X-linked gene product ATRX is required for proper replication restart and cellular resistance to replication stress. (23329831)
2013
2
First case of dizygous twins with X-linked alpha-thalassemia/mental retardation syndrome showing wide clinical variability. (20500465)
2010
3
Decreased expression of GRAF1/OPHN-1-L in the X-linked alpha thalassemia mental retardation syndrome. (20602808)
2010
4
X-linked alpha-thalassemia/mental retardation syndrome]. (19489441)
2009
5
Phenotype-genotype characterization of alpha-thalassemia mental retardation syndrome due to isolated monosomy of 16p13.3. (18076105)
2008
6
Alpha-thalassemia/mental retardation syndrome in a 45,X male. (15633163)
2005
7
Non-skewed X-inactivation may cause mental retardation in a female carrier of X-linked alpha-thalassemia/mental retardation syndrome (ATR-X): X-inactivation study of nine female carriers of ATR-X. (16100724)
2005
8
Alpha-thalassemia/mental retardation syndrome, X-Linked (ATR-X, MIM #301040, ATR-X/XNP/XH2 gene MIM #300032). (12032728)
2002
9
Molecular genetic study of Japanese patients with X-linked alpha- thalassemia/mental retardation syndrome (ATR-X). (10995512)
2000
10
A case of X-linked alpha-thalassemia/mental retardation syndrome: analysis of hemoglobin by an automated glycated hemoglobin analyzer. (9363663)
1997
11
A Japanese patient with X-linked alpha-thalassemia/mental retardation syndrome: an additional case report. (8996969)
1996
12
The alpha-thalassemia/mental retardation syndromes. (8606626)
1996
13
Self-induced vomiting in X-linked alpha-thalassemia/mental retardation syndrome. (8967323)
1996
14
Lumping Juberg-Marsidi syndrome and X-linked alpha-thalassemia/mental retardation syndrome? (7726226)
1995
15
Clinical and hematologic aspects of the X-linked alpha-thalassemia/mental retardation syndrome (ATR-X). (7726225)
1995
16
De novo truncation of chromosome 16p and healing with (TTAGGG)n in the alpha-thalassemia/mental retardation syndrome (ATR-16). (8460633)
1993
17
X-linked alpha-thalassemia/mental retardation syndrome. Linkage analysis in a new family further supports localization in proximal Xq. (8166423)
1993
18
Alpha-thalassemia/mental retardation syndrome often confused with other disorders. (1456302)
1992
19
Clinical features and molecular analysis of the alpha thalassemia/mental retardation syndromes. II. Cases without detectable abnormality of the alpha globin complex. (2339705)
1990
20
Clinical features and molecular analysis of the alpha thalassemia/mental retardation syndromes. I. Cases due to deletions involving chromosome band 16p13.3. (2339704)
1990

Variations for Alpha-Thalassemia/mental Retardation Syndrome

About this section

UniProtKB/Swiss-Prot genetic disease variations for Alpha-Thalassemia/mental Retardation Syndrome:

64 (show all 28)
id Symbol AA change Variation ID SNP ID
1ATRXp.Pro190AlaVAR_001226
2ATRXp.Leu192PheVAR_001227
3ATRXp.Cys200SerVAR_001228
4ATRXp.Cys220ArgVAR_001229
5ATRXp.Trp222SerVAR_001230
6ATRXp.Cys243PheVAR_001231
7ATRXp.Arg246CysVAR_001232
8ATRXp.Gly249AspVAR_001233
9ATRXp.His1609ArgVAR_001234
10ATRXp.Cys1614ArgVAR_001235
11ATRXp.Lys1650AsnVAR_001236
12ATRXp.Asp2035ValVAR_001238
13ATRXp.Tyr2084HisVAR_001239
14ATRXp.Tyr2163CysVAR_001241
15ATRXp.Arg246LeuVAR_010914
16ATRXp.Gly175GluVAR_012113
17ATRXp.Asn179SerVAR_012115
18ATRXp.Pro190LeuVAR_012116
19ATRXp.Pro190SerVAR_012117
20ATRXp.Val194IleVAR_012118
21ATRXp.Gln219ProVAR_012119
22ATRXp.Gly249CysVAR_012120
23ATRXp.Val1552PheVAR_012122
24ATRXp.Leu1645SerVAR_012123
25ATRXp.Pro1713SerVAR_012124
26ATRXp.Arg1742LysVAR_012125
27ATRXp.Tyr1847CysVAR_012126
28ATRXp.Thr1621MetVAR_016916

Clinvar genetic disease variations for Alpha-Thalassemia/mental Retardation Syndrome:

6 (show all 16)
id Gene Name Type Significance SNP ID Assembly Location
1ATRXNM_000489.4(ATRX): c.4826A> G (p.His1609Arg)single nucleotide variantPathogenicrs122445093GRCh37Chr X, 76889184: 76889184
2ATRXNM_000489.4(ATRX): c.4840T> C (p.Cys1614Arg)single nucleotide variantPathogenicrs122445094GRCh37Chr X, 76889170: 76889170
3ATRXNM_000489.4(ATRX): c.4950G> T (p.Lys1650Asn)single nucleotide variantPathogenicrs122445095GRCh37Chr X, 76889060: 76889060
4ATRXNM_000489.4(ATRX): c.5579A> G (p.Asn1860Ser)single nucleotide variantPathogenicrs45439799GRCh37Chr X, 76856021: 76856021
5ATRXNM_000489.4(ATRX): c.6104A> T (p.Asp2035Val)single nucleotide variantPathogenicrs122445096GRCh37Chr X, 76849172: 76849172
6ATRXNM_000489.4(ATRX): c.6250T> C (p.Tyr2084His)single nucleotide variantPathogenicrs122445097GRCh37Chr X, 76829791: 76829791
7ATRXNM_000489.4(ATRX): c.6488A> G (p.Tyr2163Cys)single nucleotide variantPathogenicrs122445098GRCh37Chr X, 76814156: 76814156
8ATRXNM_000489.4(ATRX): c.7156C> T (p.Arg2386Ter)single nucleotide variantPathogenicrs122445099GRCh37Chr X, 76776310: 76776310
9ATRXNM_000489.4(ATRX): c.7162G> T (p.Glu2388Ter)single nucleotide variantPathogenicrs122445100GRCh37Chr X, 76776304: 76776304
10ATRXATRX, IVSAS, T-A, -10single nucleotide variantPathogenic
11ATRXATRX, 751A-Gsingle nucleotide variantPathogenic
12ATRXNM_000489.4(ATRX): c.568C> G (p.Pro190Ala)single nucleotide variantPathogenicrs122445103GRCh37Chr X, 76944337: 76944337
13ATRXATRX, ARG129CYSsingle nucleotide variantPathogenic
14ATRXNM_000489.4(ATRX): c.5225G> A (p.Arg1742Lys)single nucleotide variantPathogenicrs122445104GRCh37Chr X, 76875910: 76875910
15ATRXNM_000489.4(ATRX): c.736C> T (p.Arg246Cys)single nucleotide variantPathogenicrs122445105GRCh37Chr X, 76940012: 76940012
16ATRXNM_000489.4(ATRX): c.4862C> T (p.Thr1621Met)single nucleotide variantPathogenicrs122445106GRCh37Chr X, 76889148: 76889148

Expression for genes affiliated with Alpha-Thalassemia/mental Retardation Syndrome

About this section
Expression patterns in normal tissues for genes affiliated with Alpha-Thalassemia/mental Retardation Syndrome

Search GEO for disease gene expression data for Alpha-Thalassemia/mental Retardation Syndrome.

Pathways for genes affiliated with Alpha-Thalassemia/mental Retardation Syndrome

About this section

Compounds for genes affiliated with Alpha-Thalassemia/mental Retardation Syndrome

About this section
Sources:
44Novoseek, 24HMDB, 61Tocris Bioscience, 11DrugBank
See all sources

Compounds related to Alpha-Thalassemia/mental Retardation Syndrome according to GeneCards/GeneDecks:

idCompoundScoreTop Affiliating Genes
1p003449.4CREBBP, MECP2
2hpaii449.3WT1, MECP2
3cytosine44 2410.0WT1, MECP2, ATRX
4alanine449.0CREBBP, RPS6KA3, MECP2
5lysine448.7WT1, CREBBP, RPS6KA3
6testosterone44 61 24 1111.6MECP2, CREBBP, WT1
7arginine448.5WT1, CREBBP, MECP2
8zinc44 249.4ATRX, MECP2, CREBBP, WT1
9threonine448.3RPS6KA3, CREBBP, WT1

GO Terms for genes affiliated with Alpha-Thalassemia/mental Retardation Syndrome

About this section

Biological processes related to Alpha-Thalassemia/mental Retardation Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1histone methylationGO:0165719.4MECP2, NSD1
2response to hypoxiaGO:0016669.4CREBBP, MECP2
3histone acetylationGO:0165739.1CREBBP, MECP2
4positive regulation of transcription, DNA-templatedGO:0458938.1WT1, CREBBP, MECP2, NSD1
5negative regulation of transcription from RNA polymerase II promoterGO:0001228.1NSD1, MECP2, CREBBP, WT1

Molecular functions related to Alpha-Thalassemia/mental Retardation Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1chromatin bindingGO:0036828.2CREBBP, MECP2, NSD1, ATRX
2zinc ion bindingGO:0082708.1WT1, CREBBP, NSD1, ATRX

Products for genes affiliated with Alpha-Thalassemia/mental Retardation Syndrome

About this section
  • Antibodies
  • Proteins
  • Lysates

Sources for Alpha-Thalassemia/mental Retardation Syndrome

About this section
3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet