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Tight skin contracture syndrome, lethal



Other Names:
Hyperkeratosis-contracture syndrome; Restrictive dermopathy, lethal; Fetal hypokinesia sequence due to restrictive dermopathy
Categories:

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 1662

Definition
A congenital genodermatosis with skin/mucosae involvement, 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) and pulmonary hypoplasia without neurological abnormalities.

Epidemiology
To date, approximately 80 children with restrictive dermopathy (RD) have been described in the world literature.

Clinical description
RD is a congenital disorder and newborns are usually born prematurely (due to premature rupture of membranes with delivery at about 30-32 weeks of gestation). They present at birth with a very typical and recognizable clinical phenotype including tight, thin, rigid and translucent skin with epidermal hyperkeratosis and shedding, erosions and scaling at flexure sites, protruding nipples. Skeletal defects include: bone mineralization defects, large fontanelles, thin dysplastic clavicles, narrow chest, overtubulated long bones, generalized arthrogryposis with rocker-bottom feet. Facial dysmorphism is also characteristic and includes telecanthus, short, down-slanting palpebral fissures, sparse/absent eyelashes and eyebrows, a small and pinched nose, posteriorly rotated low-set ears, retromicrognathism and a small mouth fixed in the ''O'' position with expressionless facies. Additional features may include congenital anonychia, neonatal teeth, ectropion, choanal atresia, patent ductus arteriosus, interatrial septal defects, kyphoscoliosis, camptodactyly, hypospadias (males), ureteral duplication, adrenal hypoplasia. Intrauterine growth retardation (IUGR) with polyhydramnios, and decreased fetal movements are almost always reported. Pulmonary hypoplasia most often leads to respiratory insufficiency and death. Neither structural central nervous system nor visceral defects occur in RD.

Etiology
RD can be caused by heterozygous, de novo mutations of the LMNA gene (primary Laminopathy) or, much more frequently, by homozygous or compound heterozygous null mutations of the ZMPSTE24 gene (secondary Laminopathy). Defects in ZMPSTE24 impair the processing of Prelamin A into mature Lamin A, causing the massive intranuclear accumulation of wild type Prelamin A which exerts sytemic toxic effects and leads to the development of RD.

Diagnostic methods
The diagnosis is based upon physical examination at birth and skin histology (flat dermis with paucity/hypoplasia of appendages, abnormally dense collagen bundles parallel to the dermo-epidermic basal lamina and almost total depletion of elastic fibers), cerebral imagery, blood analysis. Molecular genetic testing for mutations confirms the diagnosis and allows genetic counselling.

Differential diagnosis
Yunis-varon syndrome, Neu-laxova syndrome, Pena-Shokeir syndrome, cerebrooculofacioskeletal syndrome, Paraná hard-skin syndrome, aplasia cutis congenita, lethal multiple pterygium syndrome.

Antenatal diagnosis
Earliest manifestations are only apparent in the late second trimester/early third trimester and include intrauterine growth retardation, decreased fetal movements, eventual joint contractures, and mouth fixed in an 'O' position. However, these signs are too nonspecific to suggest the diagnosis prenatally in cases with no family history.

Genetic counseling
The ZMPSTE24 mutations are inherited recessively, leading to the possibility of genetic counseling and prenatal diagnosis for further pregnancies if the molecular bases of the disease are identified (25% risk of having an affected child for two mutation carriers). The rare dominant mutations in the LMNA gene are de novo and the risk of recurrence of the disorder is very low (eventual germinal mosaicism).

Management and treatment
Corticosteroids are administered for fetal lung maturation. Gavage feeding may be necessary. Supportive treatment consists of mechanical ventilation, broad-spectrum antibiotics, parenteral nutrition, and intravenous analgesia.

Prognosis
The affected babies who are liveborn often die within the first week of life.

Visit the Orphanet disease page for more resources.
Last updated: 6/1/2019

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 77 |
Medical Terms Other Names
Learn More:
HPO ID
100% of people have these symptoms
Stiff skin 0030053
80%-99% of people have these symptoms
Abnormal cellular phenotype 0025354
Aplasia/Hypoplasia involving the nose
Decreased nasal size
Decreased size of nose
[ more ]
0009924
Aplasia/Hypoplasia of the clavicles
Absent/small collarbone
Absent/underdeveloped collarbone
[ more ]
0006710
Aplasia/Hypoplastia of the eccrine sweat glands 0007592
Arthrogryposis multiplex congenita 0002804
Decreased fetal movement
Less than 10 fetal movements in 12 hours
0001558
Decreased skull ossification
Decreased bone formation of skull
0004331
Dermal atrophy
Skin degeneration
0004334
Dermal translucency 0010648
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Entropion
Eyelid turned in
0000621
Epidermal hyperkeratosis
Increased thickness of skin epidermis
0007543
Generalized hyperkeratosis 0005595
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ]
0000316
Increased anterioposterior diameter of thorax 0005253
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation
[ more ]
0001511
Low-set ears
Low set ears
Lowset ears
[ more ]
0000369
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ]
0000347
Multiple joint contractures 0002828
Narrow mouth
Small mouth
0000160
Osteopenia 0000938
Patent ductus arteriosus 0001643
Premature delivery because of cervical insufficiency or membrane fragility 0005267
Pulmonary hypoplasia
Small lung
Underdeveloped lung
[ more ]
0002089
Scaling skin
flaking skin
peeling skin
scaly skin
[ more ]
0040189
Short palpebral fissure
Short opening between the eyelids
0012745
Short umbilical cord 0001196
Skin erosion 0200041
Small placenta 0006266
Sparse eyebrow
Sparse eyebrows
0045075
Sparse hair 0008070
Sparse or absent eyelashes 0200102
Structural foot deformity 0010219
Submucous cleft hard palate 0000176
Telecanthus
Corners of eye widely separated
0000506
Temporomandibular joint ankylosis
Freezing of jaw joint
0012478
Thin clavicles
Thin collarbone
0006645
Thin ribs
Slender ribs
0000883
Widely patent fontanelles and sutures 0004492
5%-29% of people have these symptoms
Ascending tubular aorta aneurysm
Bulging of wall of large artery located above heart
0004970
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers
[ more ]
0001631
Camptodactyly of finger
Permanent flexion of the finger
0100490
Choanal atresia
Blockage of the rear opening of the nasal cavity
Obstruction of the rear opening of the nasal cavity
[ more ]
0000453
Congenital adrenal hypoplasia 0008244
Dextrocardia
Heart tip and four chambers point towards right side of body
0001651
Hypospadias 0000047
Large placenta 0006267
Microcolon 0004388
Natal tooth
Born with teeth
Teeth present at birth
[ more ]
0000695
Polyhydramnios
High levels of amniotic fluid
0001561
Short nail
Short nails
0001799
Thoracic kyphoscoliosis 0005659
Transposition of the great arteries 0001669
Ureteral duplication
Double ureter
0000073
Webbed neck
Neck webbing
0000465
Percent of people who have these symptoms is not available through HPO
Abnormality of the pinna
Abnormally shaped ears
Auricular malformation
Deformed ears
Malformed ears
[ more ]
0000377
Absent eyelashes
Failure of development of eyelashes
0000561
Adrenal hypoplasia
Small adrenal glands
0000835
Ankylosis 0031013
Aplasia/Hypoplasia of the eyebrow
Absence of eyebrow
Lack of eyebrow
Missing eyebrow
[ more ]
0100840
Autosomal recessive inheritance 0000007
Blepharophimosis
Narrow opening between the eyelids
0000581
Congenital pseudoarthrosis of the clavicle 0006585
Decreased calvarial ossification
Soft skullcap
0005474
Flexion contracture
Flexed joint that cannot be straightened
0001371
Hydropic placenta 0011414
Kyphoscoliosis 0002751
Large fontanelles
Wide fontanelles
0000239
Narrow nasal ridge
Decreased width of nasal ridge
Pinched nose
Thin nasal ridge
[ more ]
0000418
Overtubulated long bones 0006391
Premature birth
Premature delivery of affected infants
Preterm delivery
[ more ]
0001622
Premature rupture of membranes 0001788
Prominent superficial blood vessels
Prominent superficial vasculature
0007394
Rocker bottom foot
Rocker bottom feet
Rocker-bottom feet
Rockerbottom feet
[ more ]
0001838
Sparse eyelashes
Scant eyelashes
Scanty eyelashes
Thin eyelashes
[ more ]
0000653
Stillbirth
Stillborn
0003826
Showing of 77 |
Last updated: 7/1/2020

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If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources


These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Tight skin contracture syndrome, lethal. Click on the link to view a sample search on this topic.

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