Wrinkly skin syndrome

Title

Categories:

Congenital and Genetic Diseases; Digestive Diseases; Eye diseases; Congenital and Genetic Diseases; Digestive Diseases; Eye diseases; Lung Diseases; Metabolic disorders; Musculoskeletal Diseases; Nervous System Diseases; Skin Diseases See More

Summary Summary

Wrinkly skin syndrome is a genetic condition characterized by sagging or wrinkly skin, reduced skin elasticity, and delayed closure of the fontanel (a baby's "soft spot" on the top of his/her head). Other associated signs and symptoms vary widely. Case reports suggest that this condition is often inherited in an autosomal recessive fashion. It can be caused by mutations in the ATP6VOA2 gene. Wrinkly skin syndrome appears to be represent the mild version of autosomal recessive cutis laxa syndrome type 2.^[1]^[2]^[3]

Last updated: 11/21/2016

Symptoms Symptoms

Common signs and symptoms of wrinkly skin syndrome include wrinkled and inelastic skin on the face, backs of hands, tops of feet, and abdomen, and delayed closure of the fontanel (a baby's "soft spot" on the top of his/her head).^[1]^[2]^[3] Additional signs and symptoms that have been described in individual cases, include:^[1]^[3]

Small head size (microcephaly)
Unusual facial characteristics
Downslanting eyes
Delayed motor development
Intellectual disability
Hip dislocation
Joint laxity, subluxation (a tendon slips out of its normal position)
Hernias
Growth delay

Online Mendelian Inheritance in Man (OMIM) lists additional signs and symptoms that have been described in people with wrinkly skin syndrome.

Last updated: 11/21/2016

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.

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Medical Terms	Other Names	Learn More: HPO ID
100% of people have these symptoms
Excessive skin wrinkling on dorsum of hands and fingers	Excessive skin wrinkling on back of hands and fingers	0007407
80%-99% of people have these symptoms
Abnormal isoelectric focusing of serum transferrin		0003160
Abnormality of the cheek	Abnormality of the cheeks	0004426
Broad nasal tip	Broad tip of nose Broad, upturned nose Increased breadth of nasal tip Increased breadth of tip of nose Increased width of nasal tip Increased width of tip of nose Nasal tip, broad Nasal tip, wide Wide tip of nose [ more ]	0000455
Carious teeth	Dental cavities Tooth cavities Tooth decay [ more ]	0000670
Congenital hip dislocation	Dislocated hip since birth	0001374
Coxa vara		0002812
Cryptorchidism	Undescended testes Undescended testis [ more ]	0000028
Cutis laxa		0000973
Decreased muscle mass	Underdeveloped muscles	0003199
Deep palmar crease	Deep palm line	0006191
Deep plantar creases		0001869
Delayed closure of the anterior fontanelle		0001476
Delayed eruption of teeth	Delayed eruption Delayed teeth eruption Delayed tooth eruption Eruption, delayed Late eruption of teeth Late tooth eruption [ more ]	0000684
Delayed speech and language development	Deficiency of speech development Delayed language development Delayed speech Delayed speech acquisition Delayed speech development Impaired speech and language development Impaired speech development Language delay Language delayed Language development deficit Late-onset speech development Poor language development Speech and language delay Speech and language difficulties Speech delay [ more ]	0000750
Downslanted palpebral fissures	Downward slanting of the opening between the eyelids	0000494
Epicanthus	Eye folds Prominent eye folds [ more ]	0000286
Failure to thrive	Faltering weight Weight faltering [ more ]	0001508
Fragmented elastic fibers in the dermis		0025167
Generalized joint laxity	Increased joint mobility	0002761
Global developmental delay		0001263
High myopia	Severe near sightedness Severely close sighted Severely near sighted [ more ]	0011003
High nonceruloplasmin-bound serum copper		0010838
High palate	Elevated palate Increased palatal height [ more ]	0000218
Hypertelorism	Wide-set eyes Widely spaced eyes [ more ]	0000316
Infantile muscular hypotonia	Decreased muscle tone in infant	0008947
Inguinal hernia		0000023
Intrauterine growth retardation	Prenatal growth deficiency Prenatal growth retardation [ more ]	0001511
Kyphoscoliosis		0002751
Lipodystrophy		0009125
Long philtrum		0000343
Low-set ears	Low set ears Lowset ears [ more ]	0000369
Multiple palmar creases	Multiple palm lines	0006114
Multiple plantar creases		0008113
Nasal speech	Nasal voice	0001611
Osteopenia		0000938
Pectus excavatum	Funnel chest	0000767
Pes planus	Flat feet Flat foot [ more ]	0001763
Postnatal growth retardation	Growth delay as children	0008897
Premature rupture of membranes		0001788
Progressive microcephaly	Progressively abnormally small cranium Progressively abnormally small skull [ more ]	0000253
Prominent nasolabial fold	Deep laugh lines Deep smile lines Prominent laugh lines Prominent smile lines [ more ]	0005272
Prominent veins on trunk		0007457
Recurrent sinopulmonary infections		0005425
Short stature	Decreased body height Small stature [ more ]	0004322
Slender long bones with narrow diaphyses	Slender long bones with narrow shaft	0004993
Small, conical teeth	Small, cone shaped teeth	0200141
Smooth philtrum		0000319
Sparse hair		0008070
Thick cerebral cortex		0006891
Umbilical hernia		0001537
Wormian bones	Extra bones within cranial sutures	0002645
30%-79% of people have these symptoms
Atrial septal dilatation		0011995
Dandy-Walker malformation		0001305
Progressive cerebellar ataxia		0002073
Slurred speech		0001350
Status epilepticus		0002133
5%-29% of people have these symptoms
Abnormality of the intrinsic pathway		0010989
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance		0000007
Delayed cranial suture closure		0000270
Fragile nails	Brittle nails	0001808
Hypoplasia of the musculature	Poorly developed skeletal musculature Underdeveloped muscle [ more ]	0009004
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Joint hypermobility	Double-Jointed Flexible joints Increased mobility of joints [ more ]	0001382
Kyphosis	Hunched back Round back [ more ]	0002808
Microcephaly	Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ]	0000252
Microdontia	Decreased width of tooth	0000691
Muscular hypotonia	Low or weak muscle tone	0001252
Neonatal wrinkled skin of hands and feet	Wrinkled skin of hands and feet in newborn	0007414
Palmoplantar cutis laxa	Excessive wrinkled skin of palms and soles Increased wrinkles of palms and soles Wrinkled palms and soles Wrinkled skin of hands and feet [ more ]	0007517
Scapular winging	Winged shoulder blade	0003691
Scoliosis	Abnormal curving of the spine	0002650
Short nail	Short nails	0001799
Slender long bone	Long bones slender Thin long bones [ more ]	0003100
Talipes equinovarus	Club feet Club foot Clubfeet Clubfoot [ more ]	0001762
Wide anterior fontanel		0000260
Wide nasal bridge	Broad nasal bridge Broad nasal root Broadened nasal bridge Increased breadth of bridge of nose Increased breadth of nasal bridge Increased width of bridge of nose Increased width of nasal bridge Nasal bridge broad Wide bridge of nose Widened nasal bridge [ more ]	0000431

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 10/1/2018

Do you have updated information on this disease? We want to hear from you.

Cause Cause

In many cases the underlying genetic cause of wrinkly skin syndrome is not known.^[4] Some cases are caused by mutations in the ATP6VOA2 gene.^[1]^[2]^[3] These gene mutations result in an abnormality in glycosylation.^[1]^[2] Glycosylation is a chemical process that occurs in your body's cells that involve attaching sugar molecules to proteins. Mutations in ATP6VOA2 can also cause autosomal recessive cutis laxa syndrome type 2 (ARCL type 2). Some consider wrinkly skin syndrome to be a mild variant of ARCL type 2.^[1]^[2]^[3]

Last updated: 11/21/2016

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Prognosis Prognosis

Unfortunately much of what is known regarding wrinkly skin syndrome comes from individual case reports. There is very limited information regarding the long term outlook for people with this syndrome. Also there can be great variability of symptoms, particularly regarding growth delay, developmental delay, and neurological abnormalities. Some affected individuals have developed seizures and mental deterioration later in life.^[5] Skin symptoms may become milder with age.^[1]^[5]

Last updated: 11/21/2016

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

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

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Cutis Laxa Internationale
138 impasse de Champs Gervais
FR-74890 Bons en Chablais
France
Telephone: +33 (0)4 56 30 74 43
E-mail: mcjlboiteux@aol.com
Website: http://www.cutislaxa.org/

Do you know of an organization? We want to hear from you.

Learn More Learn More

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.

Where to Start

The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
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 Wrinkly skin syndrome. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

Morava E, Guillard M, Lefeber DJ, Wevers RA. Autosomal recessive cutis laxa syndrome revisited. Eur J Hum Genet. 2009 Sep;17(9):1099-110.
Arora P, Chakravarty P, Khanna D, Gupta R. Cutis laxa autosomal recessive type II or wrinkly skin syndrome?. Indian Dermatol Online J. 2016 Sep-Oct; 7(5):440-442.

News & Events News & Events

News

NCATS Rare Diseases Are Not Rare! Challenge
October 9, 2018
The NIH Undiagnosed Diseases Network Expands
September 26, 2018

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References References

Morava E, Guillard M, Lefeber DJ, Wevers RA. Autosomal recessive cutis laxa syndrome revisited.. Eur J Hum Genet. 2009 Sep; 17(9):1099-1110. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2986595/.
Van Maldergem L, Dobyns W, Kornak U. ATP6V0A2-Related Cutis Laxa. GeneReviews. February 12, 2015; https://www.ncbi.nlm.nih.gov/books/NBK5200/.
Arora P, Chakravarty P, Khanna D, Gupta R. Cutis laxa autosomal recessive type II or wrinkly skin syndrome?. Indian Dermatol Online J. 2016 Sep-Oct; 7(5):440-442. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038118/.
Guillard M, Lefeber DJ, Morava E, Wevers RA. Wrinkly skin syndrome. Orphanet. July 2010; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=2834.
Kornak U et al.,. Impaired glycosylation and cutis laxa caused by mutations in the vesicular H+-ATPase subunit ATP6V0A2. Nat Genet. 2008 Jan; 40(1):32-4. http://www.ncbi.nlm.nih.gov/pubmed/18157129.