Wrinkly skin syndrome

Wrinkly skin syndrome (WSS) is a rare genetic condition.

Clinical features

It is characterized by sagging, wrinkled skin, low skin elasticity, and delayed fontanel (soft spot) closure along with a range of other symptoms.

Layers of the skin. Wrinkly skin syndrome affects both the papillary and reticular dermis.

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.

In many cases the underlying genetic cause of wrinkly skin syndrome is not known. Some cases are caused by mutations in the ATP6VOA2 gene. These gene mutations result in an abnormality in glycosylation. 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.

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

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. Skin symptoms may become milder with age.

Complications in Diagnosis

Several symptoms are shared with cutis laxa type II (CLT2) including wrinkling of skin, microcephaly, and developmental delay which has made proper diagnosis difficult in several cases. However, the severity of skin abnormalities and facial dysmorphia is greater in cutis laxa type II.

Additional Diagnostics

Accurate diagnosis of Wrinkly Skin Syndrome generally requires specialized dermatological assessment.

• x-rays to identify joint abnormalities
• ophthalmologic evaluation of hypertelorism, downslanting eyes, and myopia
• brain MRI scans to evaluate the degree of microcephaly
• genetic screening for Congenital Disorders of Glycosylation (CDG)
• skin biopsy and histological analysis
• genetic screening for mutations in the ATP6VOA2 gene

The pigmentation patterns observed in skin biopsies reveal a characteristic lack of elastic fibers in the papillary dermis and clumping of elastic fibers in the reticular dermis.

The Importance of the ATP6V0A2 Pump

Vacuolar ATPases (V-ATPase) regulate the pH of the subcellular compartments found within the endosomal membrane system.

The Function of the Golgi Apparatus in Protein Maturation

The most important subcellular structure in the context of wrinkly skin syndrome (WSS), is the Golgi apparatus.

Genetic Causes of WSS

Patients with both missense and/or nonsense mutations of the ATP6V0A2 gene have been shown to phenotypically express wrinkly skin syndrome (WSS) or autosomal recessive cutis laxa type II (ARCL II) (another cutis laxa disorder).

Aberrant Golgi Functioning and Clinical Symptoms of WSS

WSS is characterized by defects in the elastic fiber system that comprises the extracellular matrix of epidermal cells.

See also

• Ehlers–Danlos syndrome
• Cutis Laxa Type II
• List of cutaneous conditions