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Disease Profile

Wrinkly skin syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

Q82.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Categories

Congenital and Genetic Diseases; Digestive Diseases; Eye diseases;

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]

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.

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.

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
Loose and inelastic skin
0000973
Decreased muscle mass
0003199
Deep palmar crease
Deep palm line
0006191
Deep plantar creases
Deep wrinkles in soles of feet
0001869
Delayed closure of the anterior fontanelle
Later than typical closing of soft spot of skull
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
Hypermobility of all joints
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
Inability to make and keep healthy fat tissue
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
Recurrent sinus and lung 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

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]

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.

    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

      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

            References

            1. 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/.
            2. Van Maldergem L, Dobyns W, Kornak U. ATP6V0A2-Related Cutis Laxa. GeneReviews. February 12, 2015; https://www.ncbi.nlm.nih.gov/books/NBK5200/.
            3. 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/.
            4. Guillard M, Lefeber DJ, Morava E, Wevers RA. Wrinkly skin syndrome. Orphanet. July 2010; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=2834.
            5. 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. https://www.ncbi.nlm.nih.gov/pubmed/18157129.

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