Wrinkly skin syndrome (WSS) is a rare genetic condition characterized by sagging, wrinkled skin, low skin elasticity, and delayed fontanel (soft spot) closure along with a range of other symptoms. The disorder exhibits an autosomal recessive inheritance pattern with mutations in the ATP6V0A2 gene, leading to abnormal glycosylation events. There are only about 30 known cases of WSS as of 2010. Given its rarity and symptom overlap to other dermatological conditions, reaching an accurate diagnosis is difficult and requires specialized dermatological testing. Limited treatment options are available but long-term prognosis is variable from patient-to-patient, on the basis of individual case studies. Some skin symptoms recede with increasing age while progressive neurological advancement of the disorder causes seizures and mental deterioration later in life for some patients. Symptoms and signs
The predominant clinical symptoms of wrinkly skin syndrome are wrinkled and inelastic skin over the face, backs of hands/fingers, tops of feet, and abdomen, delayed closure of the fontanel (babys soft spot), and increased palmar and plantar creases in the hands and feet, respectively.Patients may experience a wide variety of symptoms (see table). The assortment of symptoms displayed and symptom severity (particularly  growth and developmental delays) vary from patient to patient. Microscopic analysis of epidermal samples of a four-month year old with WSS revealed an irregular pattern of elastic fiber distribution. Fewer elastic fibers are present in the papillary dermis and fragmented elastic fibers in the reticular dermis are observed.
In addition, retrograde transport serves a quality control function, by shuttling misfolded proteins back into the ER or retaining them within the Golgi itself until proper protein folding and maturation is completed. The activity of protein-modifying enzymes, like glycosyltransferases and glycosidases, relies on the lumenal pH of the Golgi apparatus. Cisternal pH becomes increasingly acidic (lower pH) with progression from cis- to trans- regions of the Golgi. Disruption of decreasing pH can impart significant effects on the efficiency and sequence of glycosylation events. Maintenance of the pH gradient across the Golgi is instrumental for proper post-translational modification of proteins prior to secretion. Retrograde transport and pH regulation are therefore vital to the proper functioning of 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). Some consider WSS to be a milder variant of ARCL II, but the genetic causes of WSS are not yet known. A large number of patients with WSS and ARCL II show a loss-of-function in the a2-subunit. These mutations in ATP6V0A2 are associated with defective glycan biosynthesis and defective Golgi apparatus structure. However, the exact mechanism of how mutations in the ATP6V0A2 gene lead to these effects is unclear. 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.