Epidermal samples from the same patient subjected to electron microscopy revealed that elastin fibers display abnormally high levels of fragmentation and clumping of microfibrils, with little amorphous elastin. Within collagen bundles, collagen fibrils are of irregular shape and thickness. These disruptions of the patients connective tissue play a role in the inelasticity of the skin and wrinkling. Mechanism
Importance of the ATP6V0A2 pump
Vacuolar ATPases (V-ATPase) regulate the pH of the subcellular compartments found within the endosomal membrane system. V-ATPases are multiprotein complexes composed of two functional domains, a V0 domain, and a V1 domain. The V1 domain catalyzes the hydrolysis of ATP in order to power the pumping of protons through the V0 channel, which spans the lipid bilayer of endosomal compartments. Vacuolar ATPases are also localized within the plasma membrane of both renal cells and osteoclasts. In osteoclasts, V-ATPases are required for pumping protons onto the bone surface. The protons are then used for bone resorption. In renal cells, V-ATPases are used to pump protons into the urine. This facilitates bicarbonate reabsorption into the blood. The ATP6V0A2 gene encodes the a2 isoform of the a-subunit (present in the V0 domain). The a2 subunit anchors the V-ATPase to the membrane, and it is also directly involved with proton transport. ATP6V0A2 is encoded by the ATP6V0A2 gene. The ATP6V0A2 pump is found in virtually all cells and is thought to play an important role in the process of vesicular fusion in the secretory pathway, including the secretion of extracellular matrix components.
Management
While there is no corrective cure for the disease, some symptoms can be managed therapeutically and/or monitored. Therapeutic treatment options include physical therapy to improve muscular development while patient growth and osteoporosis can be monitored via developmental assessments and bone density scans, respectively. Prognosis
Long-term progression of this disorder varies between patients. Due to therapeutic interventions for developmental symptoms, long-term outcomes are improved by diagnosis of the disorder during childhood. In some cases, dermatological symptoms subside while associated neurological symptoms may worsen with age, including frequency of seizures and mental deterioration. Epidemiology
As of January 2020, only ~ 30 cases of wrinkly skin syndrome have been reported. The majority of reported cases have come from Middle Eastern regions such as Iraq, Saudi Arabia, and Oman. Both males and females of Middle Eastern descent have been reported to be affected. Consanguineous (marriage of first-cousins) relationships are a prevalent feature of parents with children diagnosed with WSS. Such marriages and relationships are more common in Middle Eastern regions. Multiple children of the same parents have also been reported to be affected by WSS. There is currently insufficient epidemiological data to provide frequency of WSS occurrence in other ethnic groups. History
Wrinkly skin syndrome is a very rare disease that was amenable to molecular diagnosis only recently. Consequently, the history of this disease has been minimally documented. However, in 1973, "wrinkly skin syndrome" received its name because of its characterized features of exceedingly wrinkled skin in the hands and feet in Iraqui-Jewish first-cousins.