Wrinkly skin syndrome

Wrinkly skin syndrome (WSS), also known as wrinkly skin syndrome or sometimes grouped with gerodermia osteodysplastica, is a rare autosomal recessive connective tissue disorder characterized by wrinkling of the skin on the dorsum of the hands and feet, as well as on the abdomen. The condition is caused by biallelic pathogenic variants in the ATP6V0A2 gene, which encodes a subunit of the vacuolar H+-ATPase proton pump involved in vesicular acidification and protein glycosylation. The disease is apparent at birth or in early infancy and primarily affects the skin, skeletal system, and central nervous system. Key clinical features include generalized wrinkled and loose skin (particularly prominent on the hands, feet, and abdomen), decreased elastic tissue in the skin, increased palmar and plantar creases, a characteristic facial appearance with downslanting palpebral fissures, microcephaly, and musculoskeletal abnormalities such as joint hypermobility and hip dysplasia. Affected individuals may also exhibit developmental delay, intellectual disability of variable severity, and growth retardation. Some patients show a congenital disorder of glycosylation (CDG) type II pattern on transferrin isoelectric focusing, reflecting the role of ATP6V0A2 in Golgi function. There is no specific curative treatment for wrinkly skin syndrome. Management is supportive and multidisciplinary, focusing on developmental support, physical therapy for joint hypermobility, orthopedic surveillance for skeletal complications, and neurological monitoring. The skin wrinkling may improve somewhat with age. Genetic counseling is recommended for affected families. WSS shares clinical and genetic overlap with autosomal recessive cutis laxa type II (ARCL2), and some experts consider them part of a clinical spectrum.

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