CDPX2
MCID: CHN074
MIFTS: 43

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 58 76
Cdpx2 58 54 60 76 56
Chondrodysplasia Punctata, X-Linked Dominant 58 54 13
Happle Syndrome 58 54 76
Cdpxd 58 54 60
Cpxd 58 54 60
Chondrodysplasia Punctata 2 X-Linked Dominant 30 6
Conradi-Hunermann-Happle Syndrome 58 76
Conradi-Hunermann Syndrome 58 76
Chondrodysplasia Punctata, Type 2, X-Linked Dominant 41
Chondrodysplasia Punctata, X-Linked Dominant Type 74
X-Linked Dominant Chondrodysplasia Punctata 2 54
X-Linked Dominant Chondrodysplasia Punctata 60
X-Linked Chondrodysplasia Punctata Type 2 60
Chondrodystrophia Calcificans Congenita 60
Conradi-Hünermann-Happle Syndrome 60
Conrad Hunermann Happle Syndrome 54
Conradi-Hünermann Syndrome 77
Conradi Hunermann Syndrome 54
Chondrodysplasia Punctata 74
Cdpxd; Cpxd 58
Chh 76

Characteristics:

Orphanet epidemiological data:

60
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:

58
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:

33
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 : 54 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 joint dislocation and ptosis

OMIM : 58 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 : 76 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 : 77 Conradi–Hünermann syndrome is a rare type of chondrodysplasia punctata. It is associated with the EBP... 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

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

60 33 (show top 50) (show all 62)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 joint dislocation 60 33 hallmark (90%) Very frequent (99-80%) HP:0001373
2 ptosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0000508
3 kyphosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0002808
4 epicanthus 60 33 hallmark (90%) Very frequent (99-80%) HP:0000286
5 abnormality of the fingernails 60 33 hallmark (90%) Very frequent (99-80%) HP:0001231
6 erythema 60 33 hallmark (90%) Very frequent (99-80%) HP:0010783
7 hemiatrophy 60 33 hallmark (90%) Very frequent (99-80%) HP:0100556
8 congenital ichthyosiform erythroderma 60 33 hallmark (90%) Very frequent (99-80%) HP:0007431
9 scarring alopecia of scalp 60 33 hallmark (90%) Very frequent (99-80%) HP:0004552
10 optic atrophy 60 33 frequent (33%) Frequent (79-30%) HP:0000648
11 malar flattening 60 33 occasional (7.5%) Occasional (29-5%) HP:0000272
12 frontal bossing 60 33 occasional (7.5%) Occasional (29-5%) HP:0002007
13 abnormality of epiphysis morphology 60 33 occasional (7.5%) Occasional (29-5%) HP:0005930
14 cataract 60 33 occasional (7.5%) Occasional (29-5%) HP:0000518
15 hip dysplasia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001385
16 abnormality of the dentition 60 33 occasional (7.5%) Occasional (29-5%) HP:0000164
17 abnormal vertebral morphology 60 33 occasional (7.5%) Occasional (29-5%) HP:0003468
18 sensorineural hearing impairment 60 33 occasional (7.5%) Occasional (29-5%) HP:0000407
19 flat face 60 33 occasional (7.5%) Occasional (29-5%) HP:0012368
20 talipes equinovarus 60 33 occasional (7.5%) Occasional (29-5%) HP:0001762
21 microphthalmia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000568
22 rhizomelia 60 33 occasional (7.5%) Occasional (29-5%) HP:0008905
23 clinodactyly of the 5th finger 60 33 occasional (7.5%) Occasional (29-5%) HP:0004209
24 aplasia/hypoplasia of the skin 60 33 occasional (7.5%) Occasional (29-5%) HP:0008065
25 foot polydactyly 60 33 occasional (7.5%) Occasional (29-5%) HP:0001829
26 microcornea 60 33 occasional (7.5%) Occasional (29-5%) HP:0000482
27 abnormality of hair texture 60 33 occasional (7.5%) Occasional (29-5%) HP:0010719
28 postaxial polydactyly 33 occasional (7.5%) HP:0100259
29 polydactyly 33 occasional (7.5%) HP:0010442
30 short neck 33 HP:0000470
31 nystagmus 33 HP:0000639
32 failure to thrive 33 HP:0001508
33 scoliosis 33 HP:0002650
34 hearing impairment 33 HP:0000365
35 short stature 60 Very frequent (99-80%)
36 edema 33 HP:0000969
37 abnormality of the thorax 33 HP:0000765
38 concave nasal ridge 33 HP:0011120
39 epiphyseal stippling 33 HP:0010655
40 postnatal growth retardation 33 HP:0008897
41 alopecia 33 HP:0001596
42 abnormality of the pinna 33 HP:0000377
43 intellectual disability, moderate 33 HP:0002342
44 glaucoma 33 HP:0000501
45 downslanted palpebral fissures 33 HP:0000494
46 polyhydramnios 33 HP:0001561
47 patellar dislocation 33 HP:0002999
48 tracheal stenosis 33 HP:0002777
49 abnormality of pelvic girdle bone morphology 33 HP:0002644
50 hemivertebrae 33 HP:0002937

Symptoms via clinical synopsis from OMIM:

58
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

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 30 EBP

Anatomical Context for Chondrodysplasia Punctata 2, X-Linked Dominant

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

42
Bone, Skin, Eye

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:

76
# 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 80)
# Gene Variation Type Significance SNP ID Assembly Location
1 EBP NM_006579.2(EBP): c.141G> T (p.Trp47Cys) single nucleotide variant Pathogenic rs587783599 GRCh37 Chromosome X, 48382300: 48382300
2 EBP NM_006579.2(EBP): c.141G> T (p.Trp47Cys) single nucleotide variant Pathogenic rs587783599 GRCh38 Chromosome X, 48523912: 48523912
3 EBP NM_006579.2(EBP): c.182G> A (p.Trp61Ter) single nucleotide variant Pathogenic rs587783600 GRCh37 Chromosome X, 48382341: 48382341
4 EBP NM_006579.2(EBP): c.182G> A (p.Trp61Ter) single nucleotide variant Pathogenic rs587783600 GRCh38 Chromosome X, 48523953: 48523953
5 EBP NM_006579.2(EBP): c.204G> T (p.Trp68Cys) single nucleotide variant Likely pathogenic rs587783601 GRCh37 Chromosome X, 48382363: 48382363
6 EBP NM_006579.2(EBP): c.204G> T (p.Trp68Cys) single nucleotide variant Likely pathogenic rs587783601 GRCh38 Chromosome X, 48523975: 48523975
7 EBP NM_006579.2(EBP): c.214T> C (p.Cys72Arg) single nucleotide variant Likely pathogenic rs587783602 GRCh37 Chromosome X, 48382373: 48382373
8 EBP NM_006579.2(EBP): c.214T> C (p.Cys72Arg) single nucleotide variant Likely pathogenic rs587783602 GRCh38 Chromosome X, 48523985: 48523985
9 EBP NM_006579.2(EBP): c.218G> A (p.Gly73Glu) single nucleotide variant Likely pathogenic rs587783603 GRCh37 Chromosome X, 48382377: 48382377
10 EBP NM_006579.2(EBP): c.218G> A (p.Gly73Glu) single nucleotide variant Likely pathogenic rs587783603 GRCh38 Chromosome X, 48523989: 48523989
11 EBP NM_006579.2(EBP): c.292_296del (p.Ser98Thrfs) deletion Pathogenic rs587783604 GRCh37 Chromosome X, 48382451: 48382455
12 EBP NM_006579.2(EBP): c.292_296del (p.Ser98Thrfs) deletion Pathogenic rs587783604 GRCh38 Chromosome X, 48524063: 48524067
13 EBP NM_006579.2(EBP): c.299T> C (p.Leu100Pro) single nucleotide variant Likely pathogenic rs587783605 GRCh37 Chromosome X, 48382458: 48382458
14 EBP NM_006579.2(EBP): c.299T> C (p.Leu100Pro) single nucleotide variant Likely pathogenic rs587783605 GRCh38 Chromosome X, 48524070: 48524070
15 EBP NM_006579.2(EBP): c.301+2T> A single nucleotide variant Pathogenic rs587783606 GRCh37 Chromosome X, 48382462: 48382462
16 EBP NM_006579.2(EBP): c.301+2T> A single nucleotide variant Pathogenic rs587783606 GRCh38 Chromosome X, 48524074: 48524074
17 EBP NM_006579.2(EBP): c.303G> T (p.Trp101Cys) single nucleotide variant Likely pathogenic rs587783607 GRCh37 Chromosome X, 48385378: 48385378
18 EBP NM_006579.2(EBP): c.303G> T (p.Trp101Cys) single nucleotide variant Likely pathogenic rs587783607 GRCh38 Chromosome X, 48526990: 48526990
19 EBP NM_006579.2(EBP): c.304A> T (p.Lys102Ter) single nucleotide variant Pathogenic rs587783608 GRCh37 Chromosome X, 48385379: 48385379
20 EBP NM_006579.2(EBP): c.304A> T (p.Lys102Ter) single nucleotide variant Pathogenic rs587783608 GRCh38 Chromosome X, 48526991: 48526991
21 EBP NM_006579.2(EBP): c.310T> C (p.Tyr104His) single nucleotide variant Pathogenic rs587783609 GRCh37 Chromosome X, 48385385: 48385385
22 EBP NM_006579.2(EBP): c.310T> C (p.Tyr104His) single nucleotide variant Pathogenic rs587783609 GRCh38 Chromosome X, 48526997: 48526997
23 EBP NM_006579.2(EBP): c.311A> G (p.Tyr104Cys) single nucleotide variant Likely pathogenic rs587783610 GRCh37 Chromosome X, 48385386: 48385386
24 EBP NM_006579.2(EBP): c.311A> G (p.Tyr104Cys) single nucleotide variant Likely pathogenic rs587783610 GRCh38 Chromosome X, 48526998: 48526998
25 EBP NM_006579.2(EBP): c.314C> A (p.Ala105Asp) single nucleotide variant Likely pathogenic rs587783611 GRCh37 Chromosome X, 48385389: 48385389
26 EBP NM_006579.2(EBP): c.314C> A (p.Ala105Asp) single nucleotide variant Likely pathogenic rs587783611 GRCh38 Chromosome X, 48527001: 48527001
27 EBP NM_006579.2(EBP): c.320G> A (p.Gly107Glu) single nucleotide variant Likely pathogenic rs587783612 GRCh37 Chromosome X, 48385395: 48385395
28 EBP NM_006579.2(EBP): c.320G> A (p.Gly107Glu) single nucleotide variant Likely pathogenic rs587783612 GRCh38 Chromosome X, 48527007: 48527007
29 EBP NM_006579.2(EBP): c.328C> T (p.Arg110Ter) single nucleotide variant Pathogenic rs587783613 GRCh37 Chromosome X, 48385403: 48385403
30 EBP NM_006579.2(EBP): c.328C> T (p.Arg110Ter) single nucleotide variant Pathogenic rs587783613 GRCh38 Chromosome X, 48527015: 48527015
31 EBP NM_006579.2(EBP): c.331T> C (p.Tyr111His) single nucleotide variant Likely pathogenic rs587783614 GRCh37 Chromosome X, 48385406: 48385406
32 EBP NM_006579.2(EBP): c.331T> C (p.Tyr111His) single nucleotide variant Likely pathogenic rs587783614 GRCh38 Chromosome X, 48527018: 48527018
33 EBP NM_006579.2(EBP): c.382C> T (p.Leu128=) single nucleotide variant Conflicting interpretations of pathogenicity rs142881014 GRCh37 Chromosome X, 48385586: 48385586
34 EBP NM_006579.2(EBP): c.382C> T (p.Leu128=) single nucleotide variant Conflicting interpretations of pathogenicity rs142881014 GRCh38 Chromosome X, 48527198: 48527198
35 EBP NM_006579.2(EBP): c.464_465del (p.Ser155Cysfs) deletion Pathogenic rs587783615 GRCh37 Chromosome X, 48385668: 48385669
36 EBP NM_006579.2(EBP): c.464_465del (p.Ser155Cysfs) deletion Pathogenic rs587783615 GRCh38 Chromosome X, 48527280: 48527281
37 EBP NM_006579.2(EBP): c.480T> G (p.Tyr160Ter) single nucleotide variant Pathogenic rs587783616 GRCh37 Chromosome X, 48386632: 48386632
38 EBP NM_006579.2(EBP): c.480T> G (p.Tyr160Ter) single nucleotide variant Pathogenic rs587783616 GRCh38 Chromosome X, 48528244: 48528244
39 EBP NM_006579.2(EBP): c.481G> A (p.Gly161Arg) single nucleotide variant Likely pathogenic rs587783617 GRCh37 Chromosome X, 48386633: 48386633
40 EBP NM_006579.2(EBP): c.481G> A (p.Gly161Arg) single nucleotide variant Likely pathogenic rs587783617 GRCh38 Chromosome X, 48528245: 48528245
41 EBP NM_006579.2(EBP): c.511C> T (p.Arg171Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs141925556 GRCh37 Chromosome X, 48386663: 48386663
42 EBP NM_006579.2(EBP): c.511C> T (p.Arg171Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs141925556 GRCh38 Chromosome X, 48528275: 48528275
43 EBP NM_006579.2(EBP): c.527A> G (p.His176Arg) single nucleotide variant Likely pathogenic rs587783618 GRCh37 Chromosome X, 48386679: 48386679
44 EBP NM_006579.2(EBP): c.527A> G (p.His176Arg) single nucleotide variant Likely pathogenic rs587783618 GRCh38 Chromosome X, 48528291: 48528291
45 EBP NM_006579.2(EBP): c.632T> G (p.Leu211Arg) single nucleotide variant Likely pathogenic rs587783619 GRCh37 Chromosome X, 48386784: 48386784
46 EBP NM_006579.2(EBP): c.632T> G (p.Leu211Arg) single nucleotide variant Likely pathogenic rs587783619 GRCh38 Chromosome X, 48528396: 48528396
47 EBP NM_006579.2(EBP): c.687_689del (p.Lys229del) deletion Uncertain significance rs587783620 GRCh37 Chromosome X, 48386839: 48386841
48 EBP NM_006579.2(EBP): c.687_689del (p.Lys229del) deletion Uncertain significance rs587783620 GRCh38 Chromosome X, 48528451: 48528453
49 EBP NM_006579.2(EBP): c.201_203dup (p.Cys67_Trp68insCys) duplication Likely pathogenic rs797045542 GRCh38 Chromosome X, 48523972: 48523974
50 EBP NM_006579.2(EBP): c.201_203dup (p.Cys67_Trp68insCys) duplication Likely pathogenic rs797045542 GRCh37 Chromosome X, 48382360: 48382362

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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