MRXSC
MCID: MNT303
MIFTS: 37

Mental Retardation, X-Linked, Syndromic, Cabezas Type (MRXSC)

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

Aliases & Classifications for Mental Retardation, X-Linked, Syndromic, Cabezas Type

MalaCards integrated aliases for Mental Retardation, X-Linked, Syndromic, Cabezas Type:

Name: Mental Retardation, X-Linked, Syndromic, Cabezas Type 57
Cabezas Syndrome 57 20 58 72
Mental Retardation, X-Linked, Syndromic 15 57 29 13
Mental Retardation, X-Linked, with Short Stature, Hypogonadism, and Abnormal Gait 57 70
Syndromic X-Linked Mental Retardation, Cabezas Type 29 6
Mental Retardation, X-Linked, with Short Stature 57 70
X-Linked Intellectual Disability, Cabezas Type 20 58
Mrxs15 57 72
Mrxsc 57 72
Mrss 57 72
Mental Retardation X-Linked with Short Stature Small Testes Muscle Wasting and Tremor 72
Mental Retardation X-Linked, with Short Stature, Hypogonadism, and Abnormal Gait 72
Mental Retardation X-Linked with Brachydactyly and Macroglossia 72
Mental Retardation X-Linked-Hypotonic Facies Syndrome Type 2 72
Cabezas Type of X-Linked Syndromic Intellectual Disability 20
Mental Retardation, X-Linked, with Short Stature; Mrss 57
Mental Retardation X-Linked Syndromic, Cabezas Type 72
Mental Retardation, X-Linked, Syndromic 15; Mrxs15 57
Mental Retardation, X-Linked, Syndromic, Type 15 39
Intellectual Disability, X-Linked, Syndromic 15 20
Mental Retardation X-Linked, with Short Stature 72
Cul4b-Related X-Linked Intellectual Disability 20
Cabezas X-Linked Mental Retardation Syndrome 72
Mental Retardation, X-Linked, Syndromic, 15 72
Intellectual Deficit X-Linked Cabezas Type 72
Mrxhf2 72

Characteristics:

Orphanet epidemiological data:

58
x-linked intellectual disability, cabezas type
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
x-linked recessive

Miscellaneous:
dysmorphic facial features are variable


HPO:

31
mental retardation, x-linked, syndromic, cabezas type:
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


Summaries for Mental Retardation, X-Linked, Syndromic, Cabezas Type

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 85293 Definition An X-linked syndromic intellectual disability characterized by developmental delay, intellectual disability with significant speech impairment, and short stature in male patients. Variable additional clinical features have been associated, including macrocephaly, seizures, tremor, gait abnormalities, hypogonadism, truncal obesity, behavioral disturbances and unspecific facial dysmorphism.

MalaCards based summary : Mental Retardation, X-Linked, Syndromic, Cabezas Type, also known as cabezas syndrome, is related to syndromic x-linked intellectual disability cabezas type and alacrima, achalasia, and mental retardation syndrome, and has symptoms including tremor and gait ataxia. An important gene associated with Mental Retardation, X-Linked, Syndromic, Cabezas Type is CUL4B (Cullin 4B). Affiliated tissues include testes and skin, and related phenotypes are short neck and inguinal hernia

OMIM® : 57 This form of syndromic X-linked mental retardation is characterized primarily by short stature, hypogonadism, and abnormal gait, with other more variable features such as speech delay, prominent lower lip, and tremor (Cabezas et al., 2000). (300354) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Mental retardation, X-linked, syndromic, 15: A syndromic form of X-linked mental retardation characterized by severe intellectual deficit associated with short stature, craniofacial dysmorphism, small testes, muscle wasting in lower legs, kyphosis, joint hyperextensibility, pes cavus, small feet, and abnormalities of the toes. Additional neurologic manifestations include speech delay and impairment, tremor, seizures, gait ataxia, hyperactivity and decreased attention span.

Related Diseases for Mental Retardation, X-Linked, Syndromic, Cabezas Type

Diseases related to Mental Retardation, X-Linked, Syndromic, Cabezas Type via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 syndromic x-linked intellectual disability cabezas type 11.0
2 alacrima, achalasia, and mental retardation syndrome 10.0
3 hypogonadism 10.0
4 fibrosis of extraocular muscles, congenital, 1 10.0
5 scleroderma, familial progressive 10.0

Graphical network of the top 20 diseases related to Mental Retardation, X-Linked, Syndromic, Cabezas Type:



Diseases related to Mental Retardation, X-Linked, Syndromic, Cabezas Type

Symptoms & Phenotypes for Mental Retardation, X-Linked, Syndromic, Cabezas Type

Human phenotypes related to Mental Retardation, X-Linked, Syndromic, Cabezas Type:

58 31 (show top 50) (show all 82)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short neck 58 31 hallmark (90%) Very frequent (99-80%) HP:0000470
2 inguinal hernia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000023
3 open bite 58 31 hallmark (90%) Very frequent (99-80%) HP:0010807
4 intellectual disability, severe 58 31 hallmark (90%) Very frequent (99-80%) HP:0010864
5 absent speech 58 31 hallmark (90%) Very frequent (99-80%) HP:0001344
6 wide mouth 58 31 hallmark (90%) Very frequent (99-80%) HP:0000154
7 downslanted palpebral fissures 58 31 hallmark (90%) Very frequent (99-80%) HP:0000494
8 clinodactyly of the 5th finger 58 31 hallmark (90%) Very frequent (99-80%) HP:0004209
9 intellectual disability, moderate 58 31 hallmark (90%) Very frequent (99-80%) HP:0002342
10 short philtrum 58 31 hallmark (90%) Very frequent (99-80%) HP:0000322
11 hypoplasia of penis 58 31 hallmark (90%) Very frequent (99-80%) HP:0008736
12 down-sloping shoulders 58 31 hallmark (90%) Very frequent (99-80%) HP:0200021
13 small hand 58 31 hallmark (90%) Very frequent (99-80%) HP:0200055
14 synophrys 58 31 hallmark (90%) Very frequent (99-80%) HP:0000664
15 abnormal hair pattern 58 31 hallmark (90%) Very frequent (99-80%) HP:0010720
16 abnormality of earlobe 58 31 hallmark (90%) Very frequent (99-80%) HP:0000363
17 short palm 58 31 hallmark (90%) Very frequent (99-80%) HP:0004279
18 prominent nose 58 31 hallmark (90%) Very frequent (99-80%) HP:0000448
19 hyperactivity 58 31 hallmark (90%) Very frequent (99-80%) HP:0000752
20 macrocephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000256
21 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
22 tremor 58 31 very rare (1%) Frequent (79-30%) HP:0001337
23 high palate 58 31 frequent (33%) Frequent (79-30%) HP:0000218
24 short stature 58 31 frequent (33%) Frequent (79-30%) HP:0004322
25 thick lower lip vermilion 58 31 very rare (1%) Frequent (79-30%) HP:0000179
26 obesity 58 31 frequent (33%) Frequent (79-30%) HP:0001513
27 cachexia 58 31 frequent (33%) Frequent (79-30%) HP:0004326
28 sandal gap 58 31 frequent (33%) Frequent (79-30%) HP:0001852
29 blepharophimosis 58 31 frequent (33%) Frequent (79-30%) HP:0000581
30 pes cavus 58 31 frequent (33%) Frequent (79-30%) HP:0001761
31 decreased testicular size 58 31 very rare (1%) Frequent (79-30%) HP:0008734
32 broad-based gait 58 31 frequent (33%) Frequent (79-30%) HP:0002136
33 short foot 58 31 very rare (1%) Frequent (79-30%) HP:0001773
34 aggressive behavior 58 31 very rare (1%) Frequent (79-30%) HP:0000718
35 eeg abnormality 58 31 occasional (7.5%) Occasional (29-5%) HP:0002353
36 hyperhidrosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000975
37 kyphosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002808
38 microcephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000252
39 immunodeficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0002721
40 biparietal narrowing 58 31 occasional (7.5%) Occasional (29-5%) HP:0004422
41 cubitus valgus 58 31 occasional (7.5%) Occasional (29-5%) HP:0002967
42 epicanthus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000286
43 joint hyperflexibility 58 31 occasional (7.5%) Occasional (29-5%) HP:0005692
44 camptodactyly of finger 58 31 occasional (7.5%) Occasional (29-5%) HP:0100490
45 toe syndactyly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001770
46 acanthosis nigricans 58 31 occasional (7.5%) Occasional (29-5%) HP:0000956
47 hypogonadism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000135
48 brachydactyly 31 occasional (7.5%) HP:0001156
49 polymicrogyria 31 occasional (7.5%) HP:0002126
50 hypoplasia of the corpus callosum 31 occasional (7.5%) HP:0002079

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
tremor
ventriculomegaly
abnormal gait
mental retardation
ataxic gait
more
Head And Neck Mouth:
macroglossia
macrostomia
prominent lower lip

Skeletal Feet:
pes planus
brachydactyly
pes cavus
small feet
wide sandal gap

Skeletal:
joint laxity

Genitourinary External Genitalia Male:
hypospadias
small penis

Chest Breasts:
gynecomastia

Muscle Soft Tissue:
hypotonia
atrophy of the lower leg muscles

Head And Neck Ears:
malformed ears
hypoplastic ear lobes
abnormally positioned ears

Skin Nails Hair Skin:
striae

Growth Height:
short stature (5th percentile)

Voice:
impaired/absent speech

Skeletal Spine:
kyphosis

Head And Neck Nose:
depressed nasal bridge
large bulbous nose

Genitourinary Internal Genitalia Male:
cryptorchidism
small testes

Skeletal Hands:
brachydactyly
small hands

Head And Neck Face:
high forehead
prognathia
coarse face

Neurologic Behavioral Psychiatric Manifestations:
hyperactivity
mood swings
aggressive outbursts
decreased attention span

Head And Neck Head:
macrocephaly, relative

Growth Weight:
central obesity
low birthweight (<10th percentile)

Endocrine Features:
hypogonadism (in some patients)
delayed puberty (in some patients)

Head And Neck Eyes:
small, downslanting palpebral fissures

Clinical features from OMIM®:

300354 (Updated 05-Apr-2021)

UMLS symptoms related to Mental Retardation, X-Linked, Syndromic, Cabezas Type:


tremor; gait ataxia

Drugs & Therapeutics for Mental Retardation, X-Linked, Syndromic, Cabezas Type

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Impact of Education and Training of Modified Rodnan Skin Scoring on the Reliability of Test Unknown status NCT03219606
2 Optical Elastography of Systemic Sclerosis Skin Completed NCT02835196

Search NIH Clinical Center for Mental Retardation, X-Linked, Syndromic, Cabezas Type

Genetic Tests for Mental Retardation, X-Linked, Syndromic, Cabezas Type

Genetic tests related to Mental Retardation, X-Linked, Syndromic, Cabezas Type:

# Genetic test Affiliating Genes
1 Syndromic X-Linked Mental Retardation, Cabezas Type 29 CUL4B
2 Mental Retardation, X-Linked, Syndromic 15 (cabezas Type) 29

Anatomical Context for Mental Retardation, X-Linked, Syndromic, Cabezas Type

MalaCards organs/tissues related to Mental Retardation, X-Linked, Syndromic, Cabezas Type:

40
Testes, Skin

Publications for Mental Retardation, X-Linked, Syndromic, Cabezas Type

Articles related to Mental Retardation, X-Linked, Syndromic, Cabezas Type:

(show all 19)
# Title Authors PMID Year
1
Variants in CUL4B are associated with cerebral malformations. 6 57
25385192 2015
2
Mutation in CUL4B, which encodes a member of cullin-RING ubiquitin ligase complex, causes X-linked mental retardation. 57 6
17273978 2007
3
Mutations in CUL4B, which encodes a ubiquitin E3 ligase subunit, cause an X-linked mental retardation syndrome associated with aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus, and tremor. 6 57
17236139 2007
4
A new X linked mental retardation (XLMR) syndrome with short stature, small testes, muscle wasting, and tremor localises to Xq24-q25. 6 57
10978355 2000
5
Smith-Fineman-Myers syndrome: report on a large family. 57 6
8135271 1993
6
Donor splice-site mutation in CUL4B is likely cause of X-linked intellectual disability. 57
24898194 2014
7
Deletion of CUL4B leads to concordant phenotype in a monozygotic twin pair. 57
22182342 2012
8
Mutations in Cullin 4B result in a human syndrome associated with increased camptothecin-induced topoisomerase I-dependent DNA breaks. 57
20064923 2010
9
Deletion of the CUL4B gene in a boy with mental retardation, minor facial anomalies, short stature, hypogonadism, and ataxia. 57
20014135 2010
10
A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. 57
19377476 2009
11
[Fine mapping of Smith-Fineman-Myers syndrome and exclusion of GPC3, GPCR2 MST4 and GLUD2 as candidate genes]. 57
15192816 2004
12
[Linkage analysis of X-linked nuclear protein gene in Smith-Fineman-Myers syndrome]. 57
11836680 2002
13
Novel X-linked mental retardation syndrome with short stature maps to Xq24. 57
11562927 2001
14
[Mapping the gene responsible for Smith-Fineman-Myers syndrome to Xq25]. 57
10514530 1999
15
Familial X-linked mental retardation and isolated growth hormone deficiency: clinical and molecular findings. 57
8826446 1996
16
A 22.5 kb deletion in CUL4B causing Cabezas syndrome identified using CNV approach from WES data. 61
33363903 2020
17
Alu-mediated Xq24 deletion encompassing CUL4B, LAMP2, ATP1B4, TMEM255A, and ZBTB33 genes causes Danon disease in a female patient. 61
31729179 2020
18
Genome-first approach diagnosed Cabezas syndrome via novel CUL4B mutation detection. 61
28144446 2017
19
A novel nonsense mutation in CUL4B gene in three brothers with X-linked mental retardation syndrome. 61
20002452 2010

Variations for Mental Retardation, X-Linked, Syndromic, Cabezas Type

ClinVar genetic disease variations for Mental Retardation, X-Linked, Syndromic, Cabezas Type:

6 (show all 31)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CUL4B NM_003588.3(CUL4B):c.1906+1G>T SNV Pathogenic 208796 rs797044862 GRCh37: X:119672514-119672514
GRCh38: X:120538659-120538659
2 CUL4B NM_003588.3(CUL4B):c.1736_1737del (p.Thr579fs) Deletion Pathogenic 375587 rs1057519396 GRCh37: X:119673181-119673182
GRCh38: X:120539326-120539327
3 CUL4B NM_003588.3(CUL4B):c.1458_1459del (p.Val487fs) Deletion Pathogenic 523617 rs1556206910 GRCh37: X:119675495-119675496
GRCh38: X:120541640-120541641
4 CUL4B NM_001079872.2(CUL4B):c.1386del (p.Phe462fs) Deletion Pathogenic 804080 rs1602577238 GRCh37: X:119675514-119675514
GRCh38: X:120541659-120541659
5 CUL4B NM_003588.3(CUL4B):c.149C>T (p.Pro50Leu) SNV Pathogenic 208797 rs869320682 GRCh37: X:119694399-119694399
GRCh38: X:120560544-120560544
6 CUL4B NM_003588.3(CUL4B):c.1162C>T (p.Arg388Ter) SNV Pathogenic 11339 rs121434616 GRCh37: X:119678034-119678034
GRCh38: X:120544179-120544179
7 CUL4B NM_003588.3(CUL4B):c.1007_1011del (p.Ile336fs) Deletion Pathogenic 426723 rs1085307760 GRCh37: X:119678462-119678466
GRCh38: X:120544607-120544611
8 CUL4B NM_003588.3(CUL4B):c.901-2A>G SNV Pathogenic 11340 rs786200913 GRCh37: X:119679374-119679374
GRCh38: X:120545519-120545519
9 CUL4B NM_003588.3(CUL4B):c.1714C>T (p.Arg572Cys) SNV Pathogenic 11338 rs121434615 GRCh37: X:119673204-119673204
GRCh38: X:120539349-120539349
10 CUL4B NM_001079872.2(CUL4B):c.1396C>T (p.Arg466Ter) SNV Likely pathogenic 666344 rs905353542 GRCh37: X:119675504-119675504
GRCh38: X:120541649-120541649
11 CUL4B NM_001079872.2(CUL4B):c.1428G>A (p.Trp476Ter) SNV Likely pathogenic 976036 GRCh37: X:119675472-119675472
GRCh38: X:120541617-120541617
12 CUL4B NM_001079872.2(CUL4B):c.921_923delinsACC (p.Trp307_Asp308delinsTer) Indel Likely pathogenic 988709 GRCh37: X:119678496-119678498
GRCh38: X:120544641-120544643
13 CUL4B NM_001079872.2(CUL4B):c.1741+4_1741+7del Deletion Likely pathogenic 627585 rs1569389364 GRCh37: X:119673116-119673119
GRCh38: X:120539261-120539264
14 CUL4B NM_003588.3(CUL4B):c.943G>A (p.Val315Ile) SNV Uncertain significance 646026 rs367660624 GRCh37: X:119679330-119679330
GRCh38: X:120545475-120545475
15 CUL4B NM_003588.3(CUL4B):c.373C>G (p.Leu125Val) SNV Uncertain significance 533698 rs760294805 GRCh37: X:119694175-119694175
GRCh38: X:120560320-120560320
16 CUL4B NM_001079872.1(CUL4B):c.951_953TAT[1] (p.Ile319del) Microsatellite Uncertain significance 533699 rs1556214312 GRCh37: X:119678463-119678465
GRCh38: X:120544608-120544610
17 CUL4B NM_003588.3(CUL4B):c.2577G>C (p.Lys859Asn) SNV Uncertain significance 446244 rs1556181426 GRCh37: X:119664026-119664026
GRCh38: X:120530171-120530171
18 CUL4B NM_003588.3(CUL4B):c.1160A>G (p.Gln387Arg) SNV Uncertain significance 465136 rs1556213268 GRCh37: X:119678036-119678036
GRCh38: X:120544181-120544181
19 CUL4B NM_003588.3(CUL4B):c.117A>T (p.Arg39Ser) SNV Uncertain significance 465137 rs757541076 GRCh37: X:119694431-119694431
GRCh38: X:120560576-120560576
20 CUL4B NM_001079872.2(CUL4B):c.995T>C (p.Ile332Thr) SNV Uncertain significance 870383 GRCh37: X:119678424-119678424
GRCh38: X:120544569-120544569
21 CUL4B NM_003588.3(CUL4B):c.348G>T (p.Gln116His) SNV Uncertain significance 465138 rs755306871 GRCh37: X:119694200-119694200
GRCh38: X:120560345-120560345
22 CUL4B NM_001079872.2(CUL4B):c.1738T>C (p.Tyr580His) SNV Uncertain significance 852193 GRCh37: X:119673126-119673126
GRCh38: X:120539271-120539271
23 CUL4B NM_003588.3(CUL4B):c.423_431del Microsatellite Uncertain significance 504176 rs754330779 GRCh37: X:119694117-119694125
GRCh38: X:120560262-120560270
24 CUL4B NM_001079872.2(CUL4B):c.53A>G (p.Gln18Arg) SNV Uncertain significance 959482 GRCh37: X:119694441-119694441
GRCh38: X:120560586-120560586
25 CUL4B NM_001079872.2(CUL4B):c.1588T>C (p.Phe530Leu) SNV Uncertain significance 1029012 GRCh37: X:119674273-119674273
GRCh38: X:120540418-120540418
26 CUL4B NM_001079872.2(CUL4B):c.43G>A (p.Ala15Thr) SNV Uncertain significance 1029013 GRCh37: X:119694451-119694451
GRCh38: X:120560596-120560596
27 CUL4B NM_001079872.2(CUL4B):c.1598T>G (p.Phe533Cys) SNV Uncertain significance 1031339 GRCh37: X:119674263-119674263
GRCh38: X:120540408-120540408
28 CUL4B NM_001079872.2(CUL4B):c.1962G>A (p.Pro654=) SNV Benign 719923 rs185389157 GRCh37: X:119670866-119670866
GRCh38: X:120537011-120537011
29 CUL4B NM_003588.3(CUL4B):c.1911C>T (p.Cys637=) SNV Benign 194630 rs148700620 GRCh37: X:119672060-119672060
GRCh38: X:120538205-120538205
30 CUL4B NM_003588.3(CUL4B):c.2688G>A (p.Arg896=) SNV Benign 506496 rs143580749 GRCh37: X:119660670-119660670
GRCh38: X:120526815-120526815
31 CUL4B NM_003588.3(CUL4B):c.901-10del Deletion Benign 418559 rs762094686 GRCh37: X:119679382-119679382
GRCh38: X:120545527-120545527

UniProtKB/Swiss-Prot genetic disease variations for Mental Retardation, X-Linked, Syndromic, Cabezas Type:

72
# Symbol AA change Variation ID SNP ID
1 CUL4B p.Arg572Cys VAR_032274 rs121434615
2 CUL4B p.Val745Ala VAR_032275

Expression for Mental Retardation, X-Linked, Syndromic, Cabezas Type

Search GEO for disease gene expression data for Mental Retardation, X-Linked, Syndromic, Cabezas Type.

Pathways for Mental Retardation, X-Linked, Syndromic, Cabezas Type

GO Terms for Mental Retardation, X-Linked, Syndromic, Cabezas Type

Sources for Mental Retardation, X-Linked, Syndromic, Cabezas Type

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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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