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

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Abnormal isoelectric focusing of serum transferrin	-
Atrial septal dilatation	-
Autosomal recessive inheritance	-
Carious teeth	-
Congenital hip dislocation	-
Coxa vara	-
Cryptorchidism	-
Deep palmar crease	-
Deep plantar creases	-
Delayed cranial suture closure	-
Delayed eruption of teeth	-
Delayed speech and language development	-
Downslanted palpebral fissures	-
Epicanthus	-
Failure to thrive	-
Fragile nails	-
High palate	-
Hypertelorism	-
Hypoplasia of the musculature	-
Inguinal hernia	-
Intellectual disability	-
Joint hypermobility	-
Kyphosis	-
Long philtrum	-
Low-set ears	-
Microdontia	-
Muscular hypotonia	-
Nasal speech	-
Neonatal wrinkled skin of hands and feet	-
Osteopenia	-
Palmoplantar cutis laxa	-
Pectus excavatum	-
Pes planus	-
Premature rupture of membranes	-
Progressive microcephaly	-
Scapular winging	-
Scoliosis	-
Short nail	-
Slender long bone	-
Smooth philtrum	-
Sparse hair	-
Talipes equinovarus	-
Umbilical hernia	-
Wide anterior fontanel	-
Wide nasal bridge	-
Wormian bones	-

Last updated: 9/1/2017

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.

Treatment Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

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.

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

Do you have updated information on this condition? Let us know.

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? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics 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 GeneTests, 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.

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

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.

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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.