MCID: CHN039
MIFTS: 42

Chondrodysplasia Punctata, X-Linked Dominant

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

Aliases & Classifications for Chondrodysplasia Punctata, X-Linked Dominant

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

Name: Chondrodysplasia Punctata, X-Linked Dominant 54 50 13
Cdpx2 50 56 71 52
Chondrodysplasia Punctata 2 X-Linked Dominant 50 29
Happle Syndrome 50 71
Cdpxd 50 56
Cpxd 50 56
Chondrodysplasia Punctata, X-Linked Dominant Type 69
Chondrodysplasia Punctata 2, X-Linked Dominant 71
X-Linked Dominant Chondrodysplasia Punctata 56
X-Linked Chondrodysplasia Punctata Type 2 56
Chondrodystrophia Calcificans Congenita 56
Conradi-Hünermann-Happle Syndrome 56
Conradi-Hunermann-Happle Syndrome 71
Conrad Hunermann Happle Syndrome 50
Conradi Hunermann Syndrome 50
Conradi-Hunermann Syndrome 71
Chondrodysplasia Punctata 69
Chh 71

Characteristics:

Orphanet epidemiological data:

56
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:

54
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, x-linked dominant:
Onset and clinical course variable expressivity congenital onset
Inheritance x-linked dominant inheritance


Classifications:



Summaries for Chondrodysplasia Punctata, X-Linked Dominant

NIH Rare Diseases : 50 x-linked dominant chondrodysplasia punctata (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. last updated: 11/18/2011

MalaCards based summary : Chondrodysplasia Punctata, X-Linked Dominant, also known as cdpx2, is related to cartilage-hair hypoplasia and smith-lemli-opitz syndrome, and has symptoms including optic atrophy, ptosis and kyphosis. An important gene associated with Chondrodysplasia Punctata, X-Linked Dominant is EBP (Emopamil Binding Protein (Sterol Isomerase)), and among its related pathways/superpathways are Metabolism and Terpenoid backbone biosynthesis. Affiliated tissues include bone, skin and eye.

UniProtKB/Swiss-Prot : 71 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.

OMIM : 54
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)

Related Diseases for Chondrodysplasia Punctata, X-Linked Dominant

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



Diseases related to Chondrodysplasia Punctata, X-Linked Dominant

Symptoms & Phenotypes for Chondrodysplasia Punctata, X-Linked Dominant

Symptoms via clinical synopsis from OMIM:

54

Skeletal- Spine:
scoliosis
hemivertebrae
vertebral calcifications

Head And Neck- Ears:
hearing loss
dysplastic ears

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

Head And Neck- Neck:
short neck

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

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

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- Eyes:
nystagmus
cataracts
downslanting palpebral fissures
glaucoma
microphthalmos

Prenatal Manifestations- Amniotic Fluid:
polyhydramnios
hydrops

Genitourinary- Kidneys:
hydronephrosis

Skeletal- Limbs:
dislocation of patella
epiphyseal stippling
asymmetric limb shortening

Respiratory- Airways:
tracheal calcifications
tracheal stenosis

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

Skeletal- Feet:
bilateral club feet
punctate calcifications of tarsals

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, X-Linked Dominant:

56 32 (show top 50) (show all 62)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 optic atrophy 56 32 frequent (33%) Frequent (79-30%) HP:0000648
2 ptosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0000508
3 kyphosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0002808
4 microphthalmia 56 32 occasional (7.5%) Occasional (29-5%) HP:0000568
5 frontal bossing 56 32 occasional (7.5%) Occasional (29-5%) HP:0002007
6 microcornea 56 32 occasional (7.5%) Occasional (29-5%) HP:0000482
7 talipes equinovarus 56 32 occasional (7.5%) Occasional (29-5%) HP:0001762
8 cataract 56 32 occasional (7.5%) Occasional (29-5%) HP:0000518
9 flat face 56 32 occasional (7.5%) Occasional (29-5%) HP:0012368
10 rhizomelia 56 32 occasional (7.5%) Occasional (29-5%) HP:0008905
11 epicanthus 56 32 hallmark (90%) Very frequent (99-80%) HP:0000286
12 sensorineural hearing impairment 56 32 occasional (7.5%) Occasional (29-5%) HP:0000407
13 malar flattening 56 32 occasional (7.5%) Occasional (29-5%) HP:0000272
14 erythema 56 32 hallmark (90%) Very frequent (99-80%) HP:0010783
15 hip dysplasia 56 32 occasional (7.5%) Occasional (29-5%) HP:0001385
16 joint dislocation 56 32 hallmark (90%) Very frequent (99-80%) HP:0001373
17 scarring alopecia of scalp 56 32 hallmark (90%) Very frequent (99-80%) HP:0004552
18 congenital ichthyosiform erythroderma 56 32 hallmark (90%) Very frequent (99-80%) HP:0007431
19 abnormality of epiphysis morphology 56 32 occasional (7.5%) Occasional (29-5%) HP:0005930
20 abnormality of the vertebrae 56 32 occasional (7.5%) Occasional (29-5%) HP:0003468
21 abnormality of the fingernails 56 32 hallmark (90%) Very frequent (99-80%) HP:0001231
22 clinodactyly of the 5th finger 56 32 occasional (7.5%) Occasional (29-5%) HP:0004209
23 aplasia/hypoplasia of the skin 56 32 occasional (7.5%) Occasional (29-5%) HP:0008065
24 foot polydactyly 56 32 occasional (7.5%) Occasional (29-5%) HP:0001829
25 hemiatrophy 56 32 hallmark (90%) Very frequent (99-80%) HP:0100556
26 abnormality of hair texture 56 32 occasional (7.5%) Occasional (29-5%) HP:0010719
27 short stature 56 Very frequent (99-80%)
28 failure to thrive 32 HP:0001508
29 scoliosis 32 HP:0002650
30 nystagmus 32 HP:0000639
31 alopecia 32 HP:0001596
32 polyhydramnios 32 HP:0001561
33 glaucoma 32 HP:0000501
34 hydronephrosis 32 HP:0000126
35 hemivertebrae 32 HP:0002937
36 short neck 32 HP:0000470
37 dandy-walker malformation 32 HP:0001305
38 downslanted palpebral fissures 32 HP:0000494
39 edema 32 HP:0000969
40 postaxial polydactyly 32 occasional (7.5%) HP:0100259
41 postnatal growth retardation 32 HP:0008897
42 sparse eyelashes 32 HP:0000653
43 tracheal stenosis 32 HP:0002777
44 hearing impairment 32 HP:0000365
45 intellectual disability, moderate 32 HP:0002342
46 patellar dislocation 32 HP:0002999
47 erythroderma 32 HP:0001019
48 epiphyseal stippling 32 HP:0010655
49 elevated 8(9)-cholestenol 32 HP:0003465
50 elevated 8-dehydrocholesterol 32 HP:0003462

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


edema

Drugs & Therapeutics for Chondrodysplasia Punctata, X-Linked Dominant

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

Genetic Tests for Chondrodysplasia Punctata, X-Linked Dominant

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

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

Anatomical Context for Chondrodysplasia Punctata, X-Linked Dominant

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

39
Bone, Skin, Eye

Publications for Chondrodysplasia Punctata, X-Linked Dominant

Articles related to Chondrodysplasia Punctata, X-Linked Dominant:

id Title Authors Year
1
Clinical variation in X-linked dominant chondrodysplasia punctata (X-linked dominant ichthyosis). ( 16536827 )
2006

Variations for Chondrodysplasia Punctata, X-Linked Dominant

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

71
id Symbol AA change Variation ID SNP ID
1 EBP p.Glu80Lys VAR_012105 rs28936073
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, X-Linked Dominant:

6 (show all 37)
id 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.187C> T (p.Arg63Ter) single nucleotide variant Pathogenic rs104894799 GRCh37 Chromosome X, 48382346: 48382346
3 EBP NM_006579.2(EBP): c.238G> A (p.Glu80Lys) single nucleotide variant Pathogenic rs104894800 GRCh37 Chromosome X, 48382397: 48382397
4 EBP EBP, IVS3DS, G-T, +1 single nucleotide variant Pathogenic
5 EBP EBP, 1-BP DEL, 390A deletion Pathogenic
6 EBP EBP, 1-BP INS, 586A insertion Pathogenic
7 EBP NM_006579.2(EBP): c.386G> A (p.Trp129Ter) single nucleotide variant Pathogenic rs104894792 GRCh37 Chromosome X, 48385590: 48385590
8 EBP NM_006579.2(EBP): c.523C> T (p.Gln175Ter) single nucleotide variant Pathogenic rs104894793 GRCh37 Chromosome X, 48386675: 48386675
9 EBP NM_006579.2(EBP): c.587G> A (p.Trp196Ter) single nucleotide variant Pathogenic rs104894794 GRCh37 Chromosome X, 48386739: 48386739
10 EBP NM_006579.2(EBP): c.440G> A (p.Arg147His) single nucleotide variant Pathogenic rs28935174 GRCh37 Chromosome X, 48385644: 48385644
11 EBP NM_006579.2(EBP): c.141G> T (p.Trp47Cys) single nucleotide variant Pathogenic rs587783599 GRCh37 Chromosome X, 48382300: 48382300
12 EBP NM_006579.2(EBP): c.182G> A (p.Trp61Ter) single nucleotide variant Pathogenic rs587783600 GRCh37 Chromosome X, 48382341: 48382341
13 EBP NM_006579.2(EBP): c.204G> T (p.Trp68Cys) single nucleotide variant Likely pathogenic rs587783601 GRCh37 Chromosome X, 48382363: 48382363
14 EBP NM_006579.2(EBP): c.214T> C (p.Cys72Arg) single nucleotide variant Likely pathogenic rs587783602 GRCh37 Chromosome X, 48382373: 48382373
15 EBP NM_006579.2(EBP): c.218G> A (p.Gly73Glu) single nucleotide variant Likely pathogenic rs587783603 GRCh37 Chromosome X, 48382377: 48382377
16 EBP NM_006579.2(EBP): c.292_296delTCTCA (p.Ser98Thrfs) deletion Pathogenic rs587783604 GRCh38 Chromosome X, 48524063: 48524067
17 EBP NM_006579.2(EBP): c.299T> C (p.Leu100Pro) single nucleotide variant Likely pathogenic rs587783605 GRCh37 Chromosome X, 48382458: 48382458
18 EBP NM_006579.2(EBP): c.301+2T> A single nucleotide variant Pathogenic rs587783606 GRCh38 Chromosome X, 48524074: 48524074
19 EBP NM_006579.2(EBP): c.303G> T (p.Trp101Cys) single nucleotide variant Likely pathogenic rs587783607 GRCh38 Chromosome X, 48526990: 48526990
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 GRCh38 Chromosome X, 48526997: 48526997
22 EBP NM_006579.2(EBP): c.311A> G (p.Tyr104Cys) single nucleotide variant Likely pathogenic rs587783610 GRCh38 Chromosome X, 48526998: 48526998
23 EBP NM_006579.2(EBP): c.314C> A (p.Ala105Asp) single nucleotide variant Likely pathogenic rs587783611 GRCh38 Chromosome X, 48527001: 48527001
24 EBP NM_006579.2(EBP): c.320G> A (p.Gly107Glu) single nucleotide variant Likely pathogenic rs587783612 GRCh37 Chromosome X, 48385395: 48385395
25 EBP NM_006579.2(EBP): c.328C> T (p.Arg110Ter) single nucleotide variant Pathogenic rs587783613 GRCh38 Chromosome X, 48527015: 48527015
26 EBP NM_006579.2(EBP): c.331T> C (p.Tyr111His) single nucleotide variant Likely pathogenic rs587783614 GRCh37 Chromosome X, 48385406: 48385406
27 EBP NM_006579.2(EBP): c.464_465delCT (p.Ser155Cysfs) deletion Pathogenic rs587783615 GRCh37 Chromosome X, 48385668: 48385669
28 EBP NM_006579.2(EBP): c.480T> G (p.Tyr160Ter) single nucleotide variant Pathogenic rs587783616 GRCh37 Chromosome X, 48386632: 48386632
29 EBP NM_006579.2(EBP): c.481G> A (p.Gly161Arg) single nucleotide variant Likely pathogenic rs587783617 GRCh37 Chromosome X, 48386633: 48386633
30 EBP NM_006579.2(EBP): c.527A> G (p.His176Arg) single nucleotide variant Likely pathogenic rs587783618 GRCh38 Chromosome X, 48528291: 48528291
31 EBP NM_006579.2(EBP): c.632T> G (p.Leu211Arg) single nucleotide variant Likely pathogenic rs587783619 GRCh37 Chromosome X, 48386784: 48386784
32 EBP NM_006579.2(EBP): c.201_203dupCTG (p.Cys67_Trp68insCys) duplication Likely pathogenic rs797045542 GRCh37 Chromosome X, 48382360: 48382362
33 EBP NM_006579.2(EBP): c.225dupT (p.His76Serfs) duplication Pathogenic rs797045543 GRCh37 Chromosome X, 48382384: 48382384
34 EBP NM_006579.2(EBP): c.329_332dupGATA (p.Tyr111Terfs) duplication Pathogenic rs797045544 GRCh37 Chromosome X, 48385404: 48385407
35 EBP NM_006579.2(EBP): c.369_379delCATCACAGCTTinsAG (p.Ile124_Cys127delinsGly) indel Likely pathogenic rs797045545 GRCh38 Chromosome X, 48527185: 48527195
36 EBP NM_006579.2(EBP): c.423_427delCCGCCinsT (p.Arg142Serfs) indel Pathogenic rs797045546 GRCh38 Chromosome X, 48527239: 48527243
37 EBP NM_006579.2(EBP): c.484dupG (p.Asp162Glyfs) duplication Pathogenic rs797045547 GRCh38 Chromosome X, 48528248: 48528248

Expression for Chondrodysplasia Punctata, X-Linked Dominant

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

Pathways for Chondrodysplasia Punctata, X-Linked Dominant

GO Terms for Chondrodysplasia Punctata, X-Linked Dominant

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

id 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, X-Linked Dominant according to GeneCards Suite gene sharing:

id 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, X-Linked Dominant

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