MCID: RST011
MIFTS: 45

Restrictive Dermopathy, Lethal

Categories: Genetic diseases, Rare diseases, Fetal diseases, Skin diseases

Aliases & Classifications for Restrictive Dermopathy, Lethal

MalaCards integrated aliases for Restrictive Dermopathy, Lethal:

Name: Restrictive Dermopathy, Lethal 53 49 13
Hyperkeratosis-Contracture Syndrome 53 12 49 55
Lethal Tight Skin Contracture Syndrome 71 28 69
Lethal Restrictive Dermopathy 12 55 14
Restrictive Dermopathy 55 71 36
Fetal Hypokinesia Sequence Due to Restrictive Dermopathy 53 49
Tight Skin Contracture Syndrome, Lethal 53 49
Tight Skin Contracture Syndrome 12 55
Ltscs 71
Rd 71

Characteristics:

Orphanet epidemiological data:

55
restrictive dermopathy
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal; Age of death: embryofetal,infantile,stillbirth;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
genetic heterogeneity
liveborn often die within first week of life


HPO:

31
restrictive dermopathy, lethal:
Mortality/Aging stillbirth
Inheritance heterogeneous autosomal recessive inheritance


Classifications:



Summaries for Restrictive Dermopathy, Lethal

NIH Rare Diseases : 49 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1662Disease definitionRestrictive dermopathy (RD) is a neonatal lethal genetic disease characterized by very tight and thin skin with erosions and scaling, associated to a typical facial dysmorphism, arthrogryposis multiplex, fetal akinesia or hypokinesia deformation sequence (FADS) (see these terms) and pulmonary hypoplasia without neurological abnormalities.EpidemiologyTo date, approximately 80 children with RD have been described in the world literature.Clinical descriptionRD is a congenital disorder and newborns are usually born prematurely (due to premature rupture of the membranes with subsequent delivery at about 30-32 weeks of gestation) with a very tight, thin, rigid and shiny skin with erosions and scaling, epidermal hyperkeratosis, prominent skin vessels, that results in limited joint movement and restricted growth of the underlying tissues, often rupturing and lacerating at flexure sites during delivery. Facial dysmorphism is also a characteristic feature of RD and includes telecanthus, short, down-slanting palpebral fissures, sparse/absent eyelashes and eyebrows, a small and pinched nose, posteriorly rotated low-set ears, micrognathia, and mouth fixed in the ''O'' position. Additional features include congenital anonychia (see this term), narrow chest, dysplastic clavicles, rocker-bottom feet and arthrogryposis multiplex. Intrauterine growth retardation (IUGR), polyhydramnios, decreased fetal movements, FADS, large placenta, neonatal teeth, choanal atresia, pterygium colli, patent arterial duct, interauricular communication (see these terms), dorsal kyphoscoliosis, camptodactyly, hypospadias, ureteral duplication, adrenal hypoplasia, have been occasionally reported. Pulmonary hypoplasia most often leads to respiratory insufficiency and death. Neither structural central nervous system nor visceral defects occur in RD.EtiologyRD can be caused by heterozygous, de novomutations of the LMNA (1q22) gene (primary laminopathy) or, much more frequently, by homozygous null mutations of the ZMPSTE24 (1p34) gene (secondary laminopathy). Defects in ZMPSTE24 impair the processing of prelamin A into mature lamin A, leading to the massive intranuclear accumulation of prelamin A isoforms which exert toxic effects and lead to the development of RD.Genetic counselingThe rare mutations in the LMNA gene have a dominant effect (de novo, heterozygous mutations with putative, low risk of germinal mosaic in the parents) while the frequently observed ZMPSTE24 mutations are inherited recessively, leading to the possibility of prenatal diagnosis for further pregnancies (25% risk of having another affected child for two mutation carriers), if the molecular bases of the disease are identified.Visit the Orphanet disease page for more resources. Last updated: 2/20/2015

MalaCards based summary : Restrictive Dermopathy, Lethal, also known as hyperkeratosis-contracture syndrome, is related to mandibuloacral dysplasia with type a lipodystrophy and lipodystrophy, and has symptoms including hypertelorism, low-set ears and osteopenia. An important gene associated with Restrictive Dermopathy, Lethal is ZMPSTE24 (Zinc Metallopeptidase STE24), and among its related pathways/superpathways are Terpenoid backbone biosynthesis and Adipogenesis. Affiliated tissues include skin, placenta and bone, and related phenotypes are adipose tissue and craniofacial

Disease Ontology : 12 A skin disease characterized by thin, tightly adherent translucent skin with erosions at flexure sites, superficial vessels, typical facial dysmorphism, and generalized joint ankylosis that has material basis in heterozygous mutation in the LMNA gene on chromosome 1q22 or by homozygous or compound heterozygous mutation in the ZMPSTE24 gene on chromosome 1p34.

OMIM : 53 Restrictive dermopathy is a rare, lethal genodermatosis with characteristic manifestations that are easily recognizable at birth: thin, tightly adherent translucent skin with erosions at flexure sites, superficial vessels, typical facial dysmorphism, and generalized joint ankylosis. Prenatal signs can include intrauterine growth retardation, reduced fetal movements, polyhydramnios, and premature rupture of the membranes. Most infants die within the first week of life (summary by Smigiel et al., 2010). (275210)

UniProtKB/Swiss-Prot : 71 Lethal tight skin contracture syndrome: Rare disorder mainly characterized by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial features (small mouth, small pinched nose and micrognathia), sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures and an early neonatal lethal course. Liveborn children usually die within the first week of life. The overall prevalence of consanguineous cases suggested an autosomal recessive inheritance.

Wikipedia : 72 Restrictive dermopathy is a rare, lethal autosomal recessive skin condition characterized by syndromic... more...

Related Diseases for Restrictive Dermopathy, Lethal

Diseases related to Restrictive Dermopathy, Lethal via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 76)
# Related Disease Score Top Affiliating Genes
1 mandibuloacral dysplasia with type a lipodystrophy 29.8 LMNA ZMPSTE24
2 lipodystrophy 29.4 LMNA ZMPSTE24
3 gaucher ichthyosis restrictive dermopathy 12.2
4 respiratory distress syndrome in premature infants 11.8
5 reticular dysgenesis 11.6
6 radin blood group antigen 11.4
7 newborn respiratory distress syndrome 11.1
8 respiratory distress syndrome, infant 11.0
9 renal hypodysplasia/aplasia 1 10.9
10 refsum disease, classic 10.9
11 renal hypodysplasia/aplasia 2 10.9
12 adult respiratory distress syndrome 10.9
13 bronchopulmonary dysplasia 10.9
14 retinitis 10.5
15 retinitis pigmentosa 10.3
16 leber congenital amaurosis 4 10.3
17 rhabdomyosarcoma 10.3
18 retinal degeneration 10.3
19 choroiditis 10.1
20 acroosteolysis 10.0 LMNA ZMPSTE24
21 ovarian cystadenoma 10.0 LMNA ZMPSTE24
22 reynolds syndrome 10.0 LMNA ZMPSTE24
23 hallermann-streiff syndrome 10.0 LMNA ZMPSTE24
24 cone-rod dystrophy 2 10.0
25 congenital generalized lipodystrophy 9.9 LMNA ZMPSTE24
26 hutchinson-gilford progeria syndrome 9.9 LMNA ZMPSTE24
27 embryonal rhabdomyosarcoma 9.9
28 butterfly-shaped pigment dystrophy 9.9
29 neu-laxova syndrome 1 9.8
30 adrenomyodystrophy 9.8
31 arthrogryposis multiplex congenita, neurogenic, with myelin defect 9.8
32 keratopathy 9.8
33 familial partial lipodystrophy 9.8
34 pustulosis of palm and sole 9.8
35 psoriasis 9.8
36 macular degeneration, age-related, 1 9.8
37 mycobacterium tuberculosis 1 9.8
38 retinal disease 9.8
39 alopecia 9.8 KRT14 LMNA
40 breast cancer 9.7
41 hepatocellular carcinoma 9.7
42 epstein syndrome 9.7
43 stargardt disease 1 9.7
44 polycystic kidney disease 4 with or without hepatic disease 9.7
45 enhanced s-cone syndrome 9.7
46 squamous cell carcinoma, head and neck 9.7
47 retinitis pigmentosa 6 9.7
48 rett syndrome 9.7
49 aging 9.7
50 cervical cancer 9.7

Graphical network of the top 20 diseases related to Restrictive Dermopathy, Lethal:



Diseases related to Restrictive Dermopathy, Lethal

Symptoms & Phenotypes for Restrictive Dermopathy, Lethal

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Eyes:
hypertelorism
entropion
short palpebral fissures
sparse/absent eyelashes
sparse/absent eyebrows

Head And Neck Mouth:
cleft palate
small mouth
submucous cleft palate
ankylosis of temporomandibular joint

Cardiovascular Vascular:
patent ductus arteriosus

Cardiovascular Heart:
atrial septal defect

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Skeletal Skull:
large fontanelles
poorly mineralized skull
widened suture

Prenatal Manifestations Delivery:
premature birth
premature rupture of membranes
stillbirth

Endocrine Features:
adrenal hypoplasia

Prenatal Manifestations Placenta And Umbilical Cord:
short umbilical cord
hydropic placenta

Skeletal Limbs:
overtubulated long bones
joint contractures

Skin Nails Hair Nails:
short nails
long nails

Head And Neck Teeth:
natal teeth

Skin Nails Hair Hair:
sparse/absent eyelashes
sparse/absent eyebrows
sparse/absent lanugo
normal scalp hair

Chest RibsSternum Clavicles And Scapulae:
thin, dysplastic bipartite clavicles
ribbon-like ribs

Head And Neck Ears:
low-set ears
dysplastic ears

Head And Neck Face:
micrognathia
expressionless facies

Growth Other:
intrauterine growth retardation

Genitourinary External Genitalia Male:
hypospadias

Head And Neck Nose:
choanal atresia
small, pinched nose

Genitourinary Ureters:
ureteral duplication

Skeletal Spine:
kyphoscoliosis

Respiratory Lung:
pulmonary hypoplasia

Skin Nails Hair Skin:
epidermal hyperkeratosis
tight, rigid skin
skin erosions
prominent superficial vasculature
skin fissures (groin, axilla, neck)
more
Head And Neck Head:
large fontanel

Skeletal Feet:
rocker-bottom feet

Prenatal Manifestations Movement:
decreased fetal activity

Chest External Features:
increased anterioposterior diameter of chest


Clinical features from OMIM:

275210

Human phenotypes related to Restrictive Dermopathy, Lethal:

55 31 (show top 50) (show all 75)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 55 31 hallmark (90%) Very frequent (99-80%) HP:0000316
2 low-set ears 55 31 hallmark (90%) Very frequent (99-80%) HP:0000369
3 osteopenia 55 31 hallmark (90%) Very frequent (99-80%) HP:0000938
4 generalized hyperkeratosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0005595
5 micrognathia 55 31 hallmark (90%) Very frequent (99-80%) HP:0000347
6 scaling skin 55 31 hallmark (90%) Very frequent (99-80%) HP:0040189
7 patent ductus arteriosus 55 31 hallmark (90%) Very frequent (99-80%) HP:0001643
8 intrauterine growth retardation 55 31 hallmark (90%) Very frequent (99-80%) HP:0001511
9 webbed neck 55 31 occasional (7.5%) Occasional (29-5%) HP:0000465
10 atrial septal defect 55 31 occasional (7.5%) Occasional (29-5%) HP:0001631
11 arthrogryposis multiplex congenita 55 31 hallmark (90%) Very frequent (99-80%) HP:0002804
12 telecanthus 55 31 hallmark (90%) Very frequent (99-80%) HP:0000506
13 microcolon 55 31 occasional (7.5%) Occasional (29-5%) HP:0004388
14 thin ribs 55 31 hallmark (90%) Very frequent (99-80%) HP:0000883
15 hypospadias 55 31 occasional (7.5%) Occasional (29-5%) HP:0000047
16 downslanted palpebral fissures 55 31 hallmark (90%) Very frequent (99-80%) HP:0000494
17 narrow mouth 55 31 hallmark (90%) Very frequent (99-80%) HP:0000160
18 polyhydramnios 55 31 occasional (7.5%) Occasional (29-5%) HP:0001561
19 choanal atresia 55 31 occasional (7.5%) Occasional (29-5%) HP:0000453
20 decreased fetal movement 55 31 hallmark (90%) Very frequent (99-80%) HP:0001558
21 camptodactyly of finger 55 31 occasional (7.5%) Occasional (29-5%) HP:0100490
22 sparse hair 55 31 hallmark (90%) Very frequent (99-80%) HP:0008070
23 ureteral duplication 55 31 occasional (7.5%) Occasional (29-5%) HP:0000073
24 dextrocardia 55 31 occasional (7.5%) Occasional (29-5%) HP:0001651
25 premature birth 55 31 Very frequent (99-80%) HP:0001622
26 large placenta 55 31 occasional (7.5%) Occasional (29-5%) HP:0006267
27 aplasia/hypoplasia involving the nose 55 31 hallmark (90%) Very frequent (99-80%) HP:0009924
28 transposition of the great arteries 55 31 occasional (7.5%) Occasional (29-5%) HP:0001669
29 decreased skull ossification 55 31 hallmark (90%) Very frequent (99-80%) HP:0004331
30 submucous cleft hard palate 55 31 hallmark (90%) Very frequent (99-80%) HP:0000176
31 skin erosion 55 31 hallmark (90%) Very frequent (99-80%) HP:0200041
32 pulmonary hypoplasia 55 31 hallmark (90%) Very frequent (99-80%) HP:0002089
33 sparse eyebrow 55 31 hallmark (90%) Very frequent (99-80%) HP:0045075
34 short palpebral fissure 55 31 hallmark (90%) Very frequent (99-80%) HP:0012745
35 aplasia/hypoplasia of the clavicles 55 31 hallmark (90%) Very frequent (99-80%) HP:0006710
36 multiple joint contractures 55 31 hallmark (90%) Very frequent (99-80%) HP:0002828
37 short nail 55 31 occasional (7.5%) Occasional (29-5%) HP:0001799
38 sparse or absent eyelashes 55 31 hallmark (90%) Very frequent (99-80%) HP:0200102
39 natal tooth 55 31 occasional (7.5%) Occasional (29-5%) HP:0000695
40 stiff skin 55 31 obligate (100%) Obligate (100%) HP:0030053
41 entropion 55 31 hallmark (90%) Very frequent (99-80%) HP:0000621
42 short umbilical cord 55 31 hallmark (90%) Very frequent (99-80%) HP:0001196
43 dermal atrophy 55 31 hallmark (90%) Very frequent (99-80%) HP:0004334
44 widely patent fontanelles and sutures 55 31 hallmark (90%) Very frequent (99-80%) HP:0004492
45 increased anterioposterior diameter of thorax 55 31 hallmark (90%) Very frequent (99-80%) HP:0005253
46 premature delivery because of cervical insufficiency or membrane fragility 55 31 hallmark (90%) Very frequent (99-80%) HP:0005267
47 small placenta 55 31 hallmark (90%) Very frequent (99-80%) HP:0006266
48 thin clavicles 55 31 hallmark (90%) Very frequent (99-80%) HP:0006645
49 epidermal hyperkeratosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0007543
50 aplasia/hypoplastia of the eccrine sweat glands 55 31 hallmark (90%) Very frequent (99-80%) HP:0007592

MGI Mouse Phenotypes related to Restrictive Dermopathy, Lethal:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 adipose tissue MP:0005375 9.76 DHCR24 KRT14 LMNA ZMPSTE24
2 craniofacial MP:0005382 9.73 AQP3 KRT14 LMNA ZMPSTE24
3 growth/size/body region MP:0005378 9.72 AQP3 DHCR24 KRT14 LMNA ZMPSTE24
4 digestive/alimentary MP:0005381 9.71 ZMPSTE24 AQP3 KRT14 LMNA
5 endocrine/exocrine gland MP:0005379 9.67 DHCR24 KRT14 LMNA ZMPSTE24
6 homeostasis/metabolism MP:0005376 9.55 AQP3 DHCR24 KRT14 LMNA ZMPSTE24
7 hearing/vestibular/ear MP:0005377 9.43 AQP3 KRT14 LMNA
8 integument MP:0010771 9.26 DHCR24 KRT14 LMNA ZMPSTE24
9 mortality/aging MP:0010768 9.02 AQP3 DHCR24 KRT14 LMNA ZMPSTE24

Drugs & Therapeutics for Restrictive Dermopathy, Lethal

Search Clinical Trials , NIH Clinical Center for Restrictive Dermopathy, Lethal

Genetic Tests for Restrictive Dermopathy, Lethal

Genetic tests related to Restrictive Dermopathy, Lethal:

# Genetic test Affiliating Genes
1 Lethal Tight Skin Contracture Syndrome 28 LMNA ZMPSTE24

Anatomical Context for Restrictive Dermopathy, Lethal

MalaCards organs/tissues related to Restrictive Dermopathy, Lethal:

38
Skin, Placenta, Bone

Publications for Restrictive Dermopathy, Lethal

Articles related to Restrictive Dermopathy, Lethal:

# Title Authors Year
1
A shared founder mutation underlies lethal restrictive dermopathy in the Austronesian aboriginal Atayal tribe of Taiwan. ( 25260550 )
2015

Variations for Restrictive Dermopathy, Lethal

ClinVar genetic disease variations for Restrictive Dermopathy, Lethal:

6 (show all 11)
# Gene Variation Type Significance SNP ID Assembly Location
1 LMNA NM_170707.3(LMNA): c.1824C> T (p.Gly608=) single nucleotide variant Pathogenic rs58596362 GRCh37 Chromosome 1, 156108404: 156108404
2 ZMPSTE24 NM_005857.4(ZMPSTE24): c.54dupT (p.Ile19Tyrfs) duplication Pathogenic rs281875361 GRCh37 Chromosome 1, 40723997: 40723997
3 ZMPSTE24 NM_005857.4(ZMPSTE24): c.591dupT (p.Ile198Tyrfs) duplication Pathogenic rs281875367 GRCh37 Chromosome 1, 40735763: 40735763
4 LMNA NM_005572.3(LMNA): c.1003C> T (p.Arg335Trp) single nucleotide variant Pathogenic/Likely pathogenic rs386134243 GRCh37 Chromosome 1, 156105758: 156105758
5 ZMPSTE24 NM_005857.4(ZMPSTE24): c.50delA (p.Lys17Serfs) deletion Pathogenic rs281875360 GRCh37 Chromosome 1, 40723993: 40723993
6 ZMPSTE24 NM_005857.4(ZMPSTE24): c.584_585delAT (p.Tyr195Phefs) deletion Pathogenic rs786205123 GRCh37 Chromosome 1, 40735756: 40735757
7 LMNA NM_170707.3(LMNA): c.1968+1G> A single nucleotide variant Pathogenic rs113436208 GRCh37 Chromosome 1, 156108549: 156108549
8 ZMPSTE24 NM_005857.4(ZMPSTE24): c.1263dupT (p.Ala422Cysfs) duplication Pathogenic rs281875375 GRCh37 Chromosome 1, 40758176: 40758176
9 ZMPSTE24 NM_005857.4(ZMPSTE24): c.1085dupT (p.Leu362Phefs) duplication Pathogenic rs137854889 GRCh37 Chromosome 1, 40756551: 40756551
10 ZMPSTE24 NM_005857.4(ZMPSTE24): c.715G> T (p.Glu239Ter) single nucleotide variant Pathogenic rs267607181 GRCh37 Chromosome 1, 40737653: 40737653
11 ZMPSTE24 NM_005857.4(ZMPSTE24): c.818delA (p.Lys273Argfs) deletion Pathogenic rs886044057 GRCh37 Chromosome 1, 40747063: 40747063

Expression for Restrictive Dermopathy, Lethal

Search GEO for disease gene expression data for Restrictive Dermopathy, Lethal.

Pathways for Restrictive Dermopathy, Lethal

Pathways related to Restrictive Dermopathy, Lethal according to KEGG:

36
# Name Kegg Source Accession
1 Terpenoid backbone biosynthesis hsa00900

GO Terms for Restrictive Dermopathy, Lethal

Cellular components related to Restrictive Dermopathy, Lethal according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 intermediate filament GO:0005882 8.62 KRT14 LMNA

Biological processes related to Restrictive Dermopathy, Lethal according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular response to hypoxia GO:0071456 8.96 AQP3 LMNA
2 nuclear envelope organization GO:0006998 8.62 LMNA ZMPSTE24

Sources for Restrictive Dermopathy, Lethal

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....