What are the other Names for this Condition? (Also known as/Synonyms)

• WSS (Wrinkly Skin Syndrome)
• Wrinkled Skin Syndrome

What is Wrinkly Skin Syndrome? (Definition/Background Information)

• Wrinkly Skin Syndrome (WSS) is a highly uncommon skin condition that is characterized by wrinkled skin and decreased elasticity of skin, along-with delayed fontanel closure (closure of the soft spot on baby’s head). The cause of WSS is due to genetic factors
• Currently, there are no well-defined treatment measures available for Wrinkly Skin Syndrome, which can present a wide range of complications involving the skin, bone, urinary, and neurological systems. The outcomes are dependent upon the severity of WSS, and can be only assessed on a case-by-case basis

Who gets Wrinkly Skin Syndrome? (Age and Sex Distribution)

• Wrinkly Skin Syndrome is an extremely rare congenital disorder with only about 30 cases being reported in the medical literature
• The presentation of symptoms may occur soon after birth or in early infancy
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Wrinkly Skin Syndrome? (Predisposing Factors)

• A positive family history may be a risk factor for Wrinkly Skin Syndrome, since some reports indicate that the disorder is inherited in an autosomal recessive manner
• Currently, no other specific risk factors have been identified for the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Wrinkly Skin Syndrome? (Etiology)

According to some reports, Wrinkly Skin Syndrome (WSS) is inherited in an autosomal recessive manner.

• Some cases are caused by mutations involving the ATP6VOA2 gene. This causes abnormalities in a cell chemical process known as glycosylation, which may result in the signs and symptoms of WSS
• Some cases of WSS are also known to be caused by mutations on the PYCR1 gene
• However, it is important to note that in a majority of cases, the involved gene is yet to be identified

Since an involvement of the ATP6VOA2 gene (that can also cause autosomal recessive cutis laxa syndrome type 2 or ARCL type 2) is noted in some cases; WSS is believed to be a mild subtype of ARCL type 2 by some researchers.

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Wrinkly Skin Syndrome?

The signs and symptoms of Wrinkly Skin Syndrome may vary in severity among the affected individuals. It may include:

• Wrinkled skin on the hands and feet
• Deep creases on the palms and soles
• The skin is not easily stretched
• Delayed fontanel closure
• Delay in appearance of baby teeth
• Tooth decays
• Hip dislocation in newborns
• Abnormalities of eyelid skin (epicanthus)
• Downslanted eyelids
• Increased distance between both eyes (hypertelorism)
• Brittle nails
• Delayed speech and language development
• Abnormal facial features including small-sized head, low-set ears, small teeth, wide nasal bridge, and sparse hair on scalp
• Poorly-developed muscles
• Clubfoot
• Umbilical and inguinal hernia

How is Wrinkly Skin Syndrome Diagnosed?

Wrinkly Skin Syndrome is diagnosed on the basis of the following information:

• Complete physical examination with evaluation of family medical history
• Dermoscopy: It is a diagnostic tool where a dermatologist examines the skin using a special magnified lens
• Wood’s lamp examination: In this procedure, the healthcare provider examines the skin using ultraviolet light. It is performed to examine the change in skin pigmentation
• Radiological imaging studies, as needed
• Bone density scan
• Skin biopsy, if necessary: A skin tissue biopsy is performed and sent to a laboratory for a pathological examination. The pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis
• Molecular genetic testing to check for or confirm specific causative gene mutation(s)
• Prenatal testing in pregnant women

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Wrinkly Skin Syndrome?

The complications of Wrinkly Skin Syndrome may include:

• Stunted growth
• Failure to thrive
• Intellectual defects
• Severe bone deformities, including scoliosis
• Hernias with associated pain
• Blockage of organs due to diverticula (gastrointestinal, urinary bladder)
• Damage to internal organs due to aortic aneurysm
• Rupture of aortic aneurysm, which can be fatal
• Severe breathing difficulties
• Recurrence of skin folds after cosmetic surgery
• Seizures
• Psychological trauma

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Wrinkly Skin Syndrome Treated?

There is no cure for Wrinkly Skin Syndrome since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops from the condition. This may include:

• Physical therapy
• Surgery to correct defects
• Occupational therapy and support
• Dental procedures for tooth conditions
• Speech and language assistance

Regular medical screening at periodic intervals with tests and physical examinations are highly recommended.

How can Wrinkly Skin Syndrome be Prevented?

Currently, Wrinkly Skin Syndrome may not be preventable since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Wrinkly Skin Syndrome? (Outcomes/Resolutions)

The prognosis of Wrinkly Skin Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any present.

• Individuals with mild conditions have better prognosis than those with severe symptoms and complications. However, the condition is known to last one’s lifetime
• The skin signs and symptoms may get better with age, although some individuals may have other complications, such as intellectual impairment and seizures, which may worsen as the individual ages

Additional and Relevant Useful Information for Wrinkly Skin Syndrome:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/healthy-living/skin-disorders/