CDPX2
MCID: CHN074
MIFTS: 46

Chondrodysplasia Punctata 2, X-Linked Dominant (CDPX2)

Categories: Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Chondrodysplasia Punctata 2, X-Linked Dominant

MalaCards integrated aliases for Chondrodysplasia Punctata 2, X-Linked Dominant:

Name: Chondrodysplasia Punctata 2, X-Linked Dominant 57 75
Cdpx2 57 53 59 75 55
Chondrodysplasia Punctata, X-Linked Dominant 57 53 13
Happle Syndrome 57 53 75
Cdpxd 57 53 59
Cpxd 57 53 59
Chondrodysplasia Punctata 2 X-Linked Dominant 29 6
Conradi-Hunermann-Happle Syndrome 57 75
Conradi-Hunermann Syndrome 57 75
Chondrodysplasia Punctata, Type 2, X-Linked Dominant 40
Chondrodysplasia Punctata, X-Linked Dominant Type 73
X-Linked Dominant Chondrodysplasia Punctata 2 53
X-Linked Dominant Chondrodysplasia Punctata 59
X-Linked Chondrodysplasia Punctata Type 2 59
Chondrodystrophia Calcificans Congenita 59
Conradi-Hünermann-Happle Syndrome 59
Conrad Hunermann Happle Syndrome 53
Conradi Hunermann Syndrome 53
Chondrodysplasia Punctata 73
Conradih�nermann Syndrome 76
Cdpxd; Cpxd 57
Chh 75

Characteristics:

Orphanet epidemiological data:

59
x-linked dominant chondrodysplasia punctata
Inheritance: X-linked dominant; Prevalence: 1-9/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

57
Miscellaneous:
variable severity
onset at birth
virtually all patients are female
surviving males are postzygotic mosaic for ebp mutations
skin erythroderma may resolve early, leaving atrophic lesions

Inheritance:
x-linked dominant


HPO:

32
chondrodysplasia punctata 2, x-linked dominant:
Onset and clinical course variable expressivity congenital onset
Inheritance x-linked dominant inheritance


Classifications:



Summaries for Chondrodysplasia Punctata 2, X-Linked Dominant

NIH Rare Diseases : 53 X-linked dominant chondrodysplasia punctata 2 (CDPX2), also known as Conradi-Hünermann-Happle syndrome, is a rare form of skeletal dysplasia characterized by skeletal malformations, skin abnormalities, cataracts and short stature. The specific symptoms and severity of the disorder may vary greatly from one individual to another. CDPX2 is caused by mutations in the emopamil binding proteingene, EBP. In many cases, this mutation occurs randomly, for no apparent reason (i.e., new mutation). The condition  is inherited as an X-linked dominant trait and occurs almost exclusively in females.Treatment of CDPX2 is directed toward the specific symptoms that present in each individual. Such treatment may require the coordinated efforts of a team of medical professionals, including physicians who diagnose and treat disorders of the skeleton, joints, muscles, and related tissues (orthopedists); skin specialists (dermatologists); eye specialists; and/or other health care professionals.

MalaCards based summary : Chondrodysplasia Punctata 2, X-Linked Dominant, also known as cdpx2, is related to chondrodysplasia punctata syndrome and cartilage-hair hypoplasia, and has symptoms including edema An important gene associated with Chondrodysplasia Punctata 2, X-Linked Dominant is EBP (EBP, Cholestenol Delta-Isomerase), and among its related pathways/superpathways are Metabolism and Terpenoid backbone biosynthesis. Affiliated tissues include bone, skin and eye, and related phenotypes are malar flattening and joint dislocation

OMIM : 57 Chondrodysplasia punctata (CDP) is a clinically and genetically heterogeneous disorder characterized by punctiform calcification of the bones. X-linked dominant CDP, also known as Conradi-Hunermann syndrome, is the most well-characterized form. CDPX2 arises almost exclusively in females and is usually lethal in males. In addition to radiographic stippling, the disorder is characterized by rhizomelic shortness, transient congenital ichthyosis following the lines of Blaschko, patchy alopecia, cataracts, and midface hypoplasia. Affected males are extremely rare and the clinical features in males almost always result from postzygotic mosaicism for an EBP mutation (summary by Aughton et al., 2003 and Arnold et al., 2012). (302960)

UniProtKB/Swiss-Prot : 75 Chondrodysplasia punctata 2, X-linked dominant: A clinically and genetically heterogeneous disorder characterized by punctiform calcification of the bones. The key clinical features of CDPX2 are chondrodysplasia punctata, linear ichthyosis, cataracts and short stature. CDPX2 is a rare disorder of defective cholesterol biosynthesis, biochemically characterized by an increased amount of 8- dehydrocholesterol and cholest-8(9)-en-3-beta-ol in the plasma and tissues.

Wikipedia : 76 Conradi�??Hünermann syndrome (also known as "Conradi�??Hünermann�??Happle syndrome", "Happle syndrome,"... more...

Related Diseases for Chondrodysplasia Punctata 2, X-Linked Dominant

Graphical network of the top 20 diseases related to Chondrodysplasia Punctata 2, X-Linked Dominant:



Diseases related to Chondrodysplasia Punctata 2, X-Linked Dominant

Symptoms & Phenotypes for Chondrodysplasia Punctata 2, X-Linked Dominant

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Neck:
short neck

Head And Neck Eyes:
nystagmus
glaucoma
downslanting palpebral fissures
cataracts
microphthalmos

Skin Nails Hair Skin:
ichthyosis
congenital ichthyosiform erythroderma
follicular atrophoderma
'orange peel' skin (large pores)
skin lesions follow the lines of blaschko

Prenatal Manifestations Amniotic Fluid:
polyhydramnios
hydrops

Genitourinary Kidneys:
hydronephrosis

Head And Neck Ears:
hearing loss
dysplastic ears

Head And Neck Nose:
saddle nose

Growth Other:
failure to thrive (early infancy)
mild to moderate growth deficiency

Skeletal Pelvis:
calcific deposits of ischium and pubis

Head And Neck Face:
frontal bossing
flat face
hypoplasia of malar eminences

Skeletal Spine:
scoliosis
hemivertebrae
vertebral calcifications

Skeletal Limbs:
epiphyseal stippling
dislocation of patella
asymmetric limb shortening

Respiratory Airways:
tracheal stenosis
tracheal calcifications

Skin Nails Hair Hair:
sparse eyelashes
sparse eyebrows
coarse, sparse hair
patchy areas of alopecia

Skeletal Feet:
bilateral club feet
punctate calcifications of tarsals

Skeletal Hands:
postaxial polydactyly (rare)
punctate calcifications of carpals

Chest Ribs Sternum Clavicles And Scapulae:
punctate calcific stippling sternum, ribs, coracoid process, and glenoid fossae of scapula

Laboratory Abnormalities:
elevated 8(9)-cholestenol
elevated 8-dehydrocholesterol


Clinical features from OMIM:

302960

Human phenotypes related to Chondrodysplasia Punctata 2, X-Linked Dominant:

59 32 (show top 50) (show all 62)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 malar flattening 59 32 occasional (7.5%) Occasional (29-5%) HP:0000272
2 joint dislocation 59 32 hallmark (90%) Very frequent (99-80%) HP:0001373
3 frontal bossing 59 32 occasional (7.5%) Occasional (29-5%) HP:0002007
4 abnormality of epiphysis morphology 59 32 occasional (7.5%) Occasional (29-5%) HP:0005930
5 ptosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0000508
6 kyphosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0002808
7 cataract 59 32 occasional (7.5%) Occasional (29-5%) HP:0000518
8 hip dysplasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001385
9 abnormality of the dentition 59 32 occasional (7.5%) Occasional (29-5%) HP:0000164
10 abnormal vertebral morphology 59 32 occasional (7.5%) Occasional (29-5%) HP:0003468
11 sensorineural hearing impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0000407
12 optic atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0000648
13 epicanthus 59 32 hallmark (90%) Very frequent (99-80%) HP:0000286
14 flat face 59 32 occasional (7.5%) Occasional (29-5%) HP:0012368
15 abnormality of the fingernails 59 32 hallmark (90%) Very frequent (99-80%) HP:0001231
16 talipes equinovarus 59 32 occasional (7.5%) Occasional (29-5%) HP:0001762
17 microphthalmia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000568
18 rhizomelia 59 32 occasional (7.5%) Occasional (29-5%) HP:0008905
19 clinodactyly of the 5th finger 59 32 occasional (7.5%) Occasional (29-5%) HP:0004209
20 aplasia/hypoplasia of the skin 59 32 occasional (7.5%) Occasional (29-5%) HP:0008065
21 foot polydactyly 59 32 occasional (7.5%) Occasional (29-5%) HP:0001829
22 erythema 59 32 hallmark (90%) Very frequent (99-80%) HP:0010783
23 microcornea 59 32 occasional (7.5%) Occasional (29-5%) HP:0000482
24 hemiatrophy 59 32 hallmark (90%) Very frequent (99-80%) HP:0100556
25 abnormality of hair texture 59 32 occasional (7.5%) Occasional (29-5%) HP:0010719
26 congenital ichthyosiform erythroderma 59 32 hallmark (90%) Very frequent (99-80%) HP:0007431
27 scarring alopecia of scalp 59 32 hallmark (90%) Very frequent (99-80%) HP:0004552
28 short neck 32 HP:0000470
29 nystagmus 32 HP:0000639
30 failure to thrive 32 HP:0001508
31 scoliosis 32 HP:0002650
32 hearing impairment 32 HP:0000365
33 short stature 59 Very frequent (99-80%)
34 edema 32 HP:0000969
35 abnormality of the thorax 32 HP:0000765
36 concave nasal ridge 32 HP:0011120
37 epiphyseal stippling 32 HP:0010655
38 postnatal growth retardation 32 HP:0008897
39 alopecia 32 HP:0001596
40 abnormality of the pinna 32 HP:0000377
41 intellectual disability, moderate 32 HP:0002342
42 glaucoma 32 HP:0000501
43 downslanted palpebral fissures 32 HP:0000494
44 polyhydramnios 32 HP:0001561
45 patellar dislocation 32 HP:0002999
46 tracheal stenosis 32 HP:0002777
47 abnormality of pelvic girdle bone morphology 32 HP:0002644
48 hemivertebrae 32 HP:0002937
49 hydronephrosis 32 HP:0000126
50 dandy-walker malformation 32 HP:0001305

UMLS symptoms related to Chondrodysplasia Punctata 2, X-Linked Dominant:


edema

Drugs & Therapeutics for Chondrodysplasia Punctata 2, X-Linked Dominant

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Novel Treatment for Syndromic Ichthyoses Withdrawn NCT01110642 Phase 2 Lovastatin

Search NIH Clinical Center for Chondrodysplasia Punctata 2, X-Linked Dominant

Genetic Tests for Chondrodysplasia Punctata 2, X-Linked Dominant

Genetic tests related to Chondrodysplasia Punctata 2, X-Linked Dominant:

# Genetic test Affiliating Genes
1 Chondrodysplasia Punctata 2 X-Linked Dominant 29 EBP

Anatomical Context for Chondrodysplasia Punctata 2, X-Linked Dominant

MalaCards organs/tissues related to Chondrodysplasia Punctata 2, X-Linked Dominant:

41
Bone, Skin, Eye, T Cells, B Cells

Publications for Chondrodysplasia Punctata 2, X-Linked Dominant

Articles related to Chondrodysplasia Punctata 2, X-Linked Dominant:

# Title Authors Year
1
Chondrodysplasia punctata (CDPX2) in a male caused by single-gene mosaicism: A 20-year follow-up. ( 30294782 )
2018
2
Clinical variation in X-linked dominant chondrodysplasia punctata (X-linked dominant ichthyosis). ( 16536827 )
2006

Variations for Chondrodysplasia Punctata 2, X-Linked Dominant

UniProtKB/Swiss-Prot genetic disease variations for Chondrodysplasia Punctata 2, X-Linked Dominant:

75
# Symbol AA change Variation ID SNP ID
1 EBP p.Glu80Lys VAR_012105 rs104894800
2 EBP p.Arg110Gln VAR_012106
3 EBP p.Arg147Gly VAR_012107
4 EBP p.Arg147His VAR_012108 rs28935174
5 EBP p.Glu103Lys VAR_074637

ClinVar genetic disease variations for Chondrodysplasia Punctata 2, X-Linked Dominant:

6 (show top 50) (show all 77)
# Gene Variation Type Significance SNP ID Assembly Location
1 EBP NM_006579.2(EBP): c.87G> A (p.Trp29Ter) single nucleotide variant Pathogenic rs104894798 GRCh37 Chromosome X, 48382246: 48382246
2 EBP NM_006579.2(EBP): c.87G> A (p.Trp29Ter) single nucleotide variant Pathogenic rs104894798 GRCh38 Chromosome X, 48523858: 48523858
3 EBP NM_006579.2(EBP): c.187C> T (p.Arg63Ter) single nucleotide variant Pathogenic rs104894799 GRCh37 Chromosome X, 48382346: 48382346
4 EBP NM_006579.2(EBP): c.187C> T (p.Arg63Ter) single nucleotide variant Pathogenic rs104894799 GRCh38 Chromosome X, 48523958: 48523958
5 EBP NM_006579.2(EBP): c.238G> A (p.Glu80Lys) single nucleotide variant Pathogenic rs104894800 GRCh37 Chromosome X, 48382397: 48382397
6 EBP NM_006579.2(EBP): c.238G> A (p.Glu80Lys) single nucleotide variant Pathogenic rs104894800 GRCh38 Chromosome X, 48524009: 48524009
7 EBP EBP, IVS3DS, G-T, +1 single nucleotide variant Pathogenic
8 EBP EBP, 1-BP DEL, 390A deletion Pathogenic
9 EBP EBP, 1-BP INS, 586A insertion Pathogenic
10 EBP NM_006579.2(EBP): c.386G> A (p.Trp129Ter) single nucleotide variant Pathogenic rs104894792 GRCh37 Chromosome X, 48385590: 48385590
11 EBP NM_006579.2(EBP): c.386G> A (p.Trp129Ter) single nucleotide variant Pathogenic rs104894792 GRCh38 Chromosome X, 48527202: 48527202
12 EBP NM_006579.2(EBP): c.523C> T (p.Gln175Ter) single nucleotide variant Pathogenic rs104894793 GRCh37 Chromosome X, 48386675: 48386675
13 EBP NM_006579.2(EBP): c.523C> T (p.Gln175Ter) single nucleotide variant Pathogenic rs104894793 GRCh38 Chromosome X, 48528287: 48528287
14 EBP NM_006579.2(EBP): c.587G> A (p.Trp196Ter) single nucleotide variant Pathogenic rs104894794 GRCh37 Chromosome X, 48386739: 48386739
15 EBP NM_006579.2(EBP): c.587G> A (p.Trp196Ter) single nucleotide variant Pathogenic rs104894794 GRCh38 Chromosome X, 48528351: 48528351
16 EBP NM_006579.2(EBP): c.440G> A (p.Arg147His) single nucleotide variant Pathogenic rs28935174 GRCh37 Chromosome X, 48385644: 48385644
17 EBP NM_006579.2(EBP): c.440G> A (p.Arg147His) single nucleotide variant Pathogenic rs28935174 GRCh38 Chromosome X, 48527256: 48527256
18 EBP NM_006579.2(EBP): c.141G> T (p.Trp47Cys) single nucleotide variant Pathogenic rs587783599 GRCh37 Chromosome X, 48382300: 48382300
19 EBP NM_006579.2(EBP): c.141G> T (p.Trp47Cys) single nucleotide variant Pathogenic rs587783599 GRCh38 Chromosome X, 48523912: 48523912
20 EBP NM_006579.2(EBP): c.182G> A (p.Trp61Ter) single nucleotide variant Pathogenic rs587783600 GRCh37 Chromosome X, 48382341: 48382341
21 EBP NM_006579.2(EBP): c.182G> A (p.Trp61Ter) single nucleotide variant Pathogenic rs587783600 GRCh38 Chromosome X, 48523953: 48523953
22 EBP NM_006579.2(EBP): c.204G> T (p.Trp68Cys) single nucleotide variant Likely pathogenic rs587783601 GRCh37 Chromosome X, 48382363: 48382363
23 EBP NM_006579.2(EBP): c.204G> T (p.Trp68Cys) single nucleotide variant Likely pathogenic rs587783601 GRCh38 Chromosome X, 48523975: 48523975
24 EBP NM_006579.2(EBP): c.214T> C (p.Cys72Arg) single nucleotide variant Likely pathogenic rs587783602 GRCh37 Chromosome X, 48382373: 48382373
25 EBP NM_006579.2(EBP): c.214T> C (p.Cys72Arg) single nucleotide variant Likely pathogenic rs587783602 GRCh38 Chromosome X, 48523985: 48523985
26 EBP NM_006579.2(EBP): c.218G> A (p.Gly73Glu) single nucleotide variant Likely pathogenic rs587783603 GRCh37 Chromosome X, 48382377: 48382377
27 EBP NM_006579.2(EBP): c.218G> A (p.Gly73Glu) single nucleotide variant Likely pathogenic rs587783603 GRCh38 Chromosome X, 48523989: 48523989
28 EBP NM_006579.2(EBP): c.292_296delTCTCA (p.Ser98Thrfs) deletion Pathogenic rs587783604 GRCh37 Chromosome X, 48382451: 48382455
29 EBP NM_006579.2(EBP): c.292_296delTCTCA (p.Ser98Thrfs) deletion Pathogenic rs587783604 GRCh38 Chromosome X, 48524063: 48524067
30 EBP NM_006579.2(EBP): c.299T> C (p.Leu100Pro) single nucleotide variant Likely pathogenic rs587783605 GRCh37 Chromosome X, 48382458: 48382458
31 EBP NM_006579.2(EBP): c.299T> C (p.Leu100Pro) single nucleotide variant Likely pathogenic rs587783605 GRCh38 Chromosome X, 48524070: 48524070
32 EBP NM_006579.2(EBP): c.301+2T> A single nucleotide variant Pathogenic rs587783606 GRCh37 Chromosome X, 48382462: 48382462
33 EBP NM_006579.2(EBP): c.301+2T> A single nucleotide variant Pathogenic rs587783606 GRCh38 Chromosome X, 48524074: 48524074
34 EBP NM_006579.2(EBP): c.303G> T (p.Trp101Cys) single nucleotide variant Likely pathogenic rs587783607 GRCh37 Chromosome X, 48385378: 48385378
35 EBP NM_006579.2(EBP): c.303G> T (p.Trp101Cys) single nucleotide variant Likely pathogenic rs587783607 GRCh38 Chromosome X, 48526990: 48526990
36 EBP NM_006579.2(EBP): c.304A> T (p.Lys102Ter) single nucleotide variant Pathogenic rs587783608 GRCh37 Chromosome X, 48385379: 48385379
37 EBP NM_006579.2(EBP): c.304A> T (p.Lys102Ter) single nucleotide variant Pathogenic rs587783608 GRCh38 Chromosome X, 48526991: 48526991
38 EBP NM_006579.2(EBP): c.310T> C (p.Tyr104His) single nucleotide variant Pathogenic rs587783609 GRCh37 Chromosome X, 48385385: 48385385
39 EBP NM_006579.2(EBP): c.310T> C (p.Tyr104His) single nucleotide variant Pathogenic rs587783609 GRCh38 Chromosome X, 48526997: 48526997
40 EBP NM_006579.2(EBP): c.311A> G (p.Tyr104Cys) single nucleotide variant Likely pathogenic rs587783610 GRCh37 Chromosome X, 48385386: 48385386
41 EBP NM_006579.2(EBP): c.311A> G (p.Tyr104Cys) single nucleotide variant Likely pathogenic rs587783610 GRCh38 Chromosome X, 48526998: 48526998
42 EBP NM_006579.2(EBP): c.314C> A (p.Ala105Asp) single nucleotide variant Likely pathogenic rs587783611 GRCh37 Chromosome X, 48385389: 48385389
43 EBP NM_006579.2(EBP): c.314C> A (p.Ala105Asp) single nucleotide variant Likely pathogenic rs587783611 GRCh38 Chromosome X, 48527001: 48527001
44 EBP NM_006579.2(EBP): c.320G> A (p.Gly107Glu) single nucleotide variant Likely pathogenic rs587783612 GRCh37 Chromosome X, 48385395: 48385395
45 EBP NM_006579.2(EBP): c.320G> A (p.Gly107Glu) single nucleotide variant Likely pathogenic rs587783612 GRCh38 Chromosome X, 48527007: 48527007
46 EBP NM_006579.2(EBP): c.328C> T (p.Arg110Ter) single nucleotide variant Pathogenic rs587783613 GRCh37 Chromosome X, 48385403: 48385403
47 EBP NM_006579.2(EBP): c.328C> T (p.Arg110Ter) single nucleotide variant Pathogenic rs587783613 GRCh38 Chromosome X, 48527015: 48527015
48 EBP NM_006579.2(EBP): c.331T> C (p.Tyr111His) single nucleotide variant Likely pathogenic rs587783614 GRCh37 Chromosome X, 48385406: 48385406
49 EBP NM_006579.2(EBP): c.331T> C (p.Tyr111His) single nucleotide variant Likely pathogenic rs587783614 GRCh38 Chromosome X, 48527018: 48527018
50 EBP NM_006579.2(EBP): c.382C> T (p.Leu128=) single nucleotide variant Conflicting interpretations of pathogenicity rs142881014 GRCh37 Chromosome X, 48385586: 48385586

Expression for Chondrodysplasia Punctata 2, X-Linked Dominant

Search GEO for disease gene expression data for Chondrodysplasia Punctata 2, X-Linked Dominant.

Pathways for Chondrodysplasia Punctata 2, X-Linked Dominant

GO Terms for Chondrodysplasia Punctata 2, X-Linked Dominant

Cellular components related to Chondrodysplasia Punctata 2, X-Linked Dominant according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum GO:0005783 9.13 EBP NSDHL STS
2 endoplasmic reticulum membrane GO:0005789 8.8 EBP NSDHL STS

Biological processes related to Chondrodysplasia Punctata 2, X-Linked Dominant according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.5 EBP NSDHL STS
2 cholesterol metabolic process GO:0008203 9.37 EBP NSDHL
3 steroid biosynthetic process GO:0006694 9.26 EBP NSDHL
4 cholesterol biosynthetic process GO:0006695 9.16 EBP NSDHL
5 sterol biosynthetic process GO:0016126 8.96 EBP NSDHL
6 steroid metabolic process GO:0008202 8.8 EBP NSDHL STS

Sources for Chondrodysplasia Punctata 2, X-Linked Dominant

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