autosomal recessive cutis laxa type 2A

Autosomal recessive cutis laxa type 2A is a connective-tissue disorder that affects the skin, joints, and several internal systems. It arises from changes in the ATP6V0A2 gene, which disrupts normal formation of elastic fibers and the processing of many proteins. Signs usually appear at birth or in early infancy and can include loose, wrinkled skin and wide-set soft skull bones. This condition is considered very rare, affecting fewer than one person in a million worldwide. Severity and symptoms vary widely between individuals.

Two findings often lead to an early diagnosis: markedly loose, wrinkled skin that makes infants look older than their age, and a persistently wide soft spot (anterior fontanel) on the skull. Many children also have joint hypermobility, allowing their joints to bend beyond the usual range. Over time, additional musculoskeletal issues such as delayed bone growth or a slender build can emerge. From a developmental perspective, some—but not all—individuals experience intellectual or broader cognitive challenges that may affect learning and daily living skills. Because this is a multi-system condition, other features can appear in a more variable manner, including feeding difficulties, growth delay, or respiratory complications. Not all individuals experience all features, and severity varies considerably.

The disorder is caused by pathogenic variants in the ATP6V0A2 gene. This gene encodes a component of the cellular proton pump that helps regulate acidity inside compartments of the cell, an essential step for building elastic tissue and properly modifying many proteins. The condition is inherited in an autosomal recessive pattern, meaning a child must receive one altered copy of ATP6V0A2 from each parent to be affected. Parents who each carry one altered copy are called carriers and are typically healthy, yet each pregnancy has a 25 percent chance of producing an affected child. The condition is more common when parents share a common ancestor because they are more likely to carry the same rare variant. Genetic counseling is recommended for families for carrier testing, family planning, and discussion of recurrence risks.

Currently, management focuses on supportive care tailored to each person’s needs. Children often benefit from physiotherapy and occupational therapy to strengthen muscles and protect overly flexible joints. Regular dermatologic care may help manage fragile skin, and nutritional support can address growth concerns. Because complications can arise in multiple organ systems, long-term care is best coordinated by a multidisciplinary team that may include dermatology, orthopedics, neurology, pulmonology, and genetics. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Families should discuss individualized monitoring schedules and available supportive services with their specialists.

Outcomes depend on the combination and severity of skin, musculoskeletal, and cognitive features in each individual. Some people achieve good mobility and independence with early therapy, whereas others may face ongoing challenges related to joint stability or developmental support. Respiratory or growth issues, when present, can also influence long-term health. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with genetic counselors, specialist clinics, and patient support networks to plan for future needs and access emerging information.