cutis laxa, autosomal recessive, type 1A

Cutis laxa, autosomal recessive, type 1A is a connective tissue disorder characterized primarily by loose, redundant skin and abnormalities of elastic fibers. The condition is caused by biallelic pathogenic variants in the FBLN5 gene, which impair the formation and function of elastic fibers in the skin and other tissues. Affected individuals typically present in early childhood with skin laxity accompanied by pulmonary complications, including emphysema and recurrent respiratory infections. As with many inherited conditions, the frequency with which this condition is recognized in the overall population is not well defined.

The clinical presentation of cutis laxa, autosomal recessive, type 1A prominently features skin abnormalities, with redundant and loose skin and premature sagging cheeks serving as hallmark signs. Pulmonary involvement is evident through emphysema and recurrent respiratory infections, and microscopic examination typically reveals abnormal cutaneous elastic fiber morphology. Additionally, a number of individuals may exhibit cardiovascular findings such as aortic regurgitation, peripheral pulmonary artery stenosis, or supravalvular aortic stenosis, while musculoskeletal issues like hypotonia and inguinal hernia occur in a subset of cases. Not all individuals experience all features, and severity varies considerably.

This condition is caused by genetic alterations in the FBLN5 gene, which encodes a protein that plays a critical role in the development and maintenance of elastic fibers in connective tissues. When both copies of the gene carry pathogenic variants, the resultant deficiency in functional fibulin-5 leads to the characteristic cutaneous laxity and compromise of the elastic components in the lungs and cardiovascular system. It is inherited in an autosomal recessive pattern, which means that each child of two carrier parents has a 25% chance of inheriting the condition. Genetic counseling is recommended for families to understand the risks and implications for family planning.

Currently, management focuses on supportive care and symptom management as there are no FDA-approved treatments specifically linked to cutis laxa, autosomal recessive, type 1A. Treatment is tailored to the individual and typically involves a multidisciplinary team that may include dermatologists, pulmonologists, cardiologists, and genetic counselors. Regular surveillance is an essential part of long-term care, helping to identify potential complications in the respiratory and cardiovascular systems before they become serious. Patients should discuss treatment options with their healthcare team to determine which therapies and monitoring strategies are most appropriate for their specific situation.

The overall outcome for individuals with cutis laxa, autosomal recessive, type 1A varies and depends on the severity of organ involvement and the timeliness and quality of supportive care received. With current standards of care, many individuals experience improved quality of life and longevity due to advances in monitoring and managing respiratory and cardiac complications. Outcomes described in medical literature continue to evolve as standards of care improve, and variability in clinical course is evident among affected individuals. Families often find it helpful to connect with specialists familiar with this condition and to seek genetic counseling for guidance on long-term care and family planning.