cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies

Cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies is a multi-system condition that affects the skin and several internal organs. It arises from biallelic mutations in the LTBP4 gene, which plays a crucial role in maintaining the integrity of connective tissue. Affected individuals typically present in early life with characteristic findings such as loose, inelastic skin along with respiratory, gastrointestinal, and urinary anomalies. This condition is very rare, affecting fewer than 1 in a million individuals.

Clinically, nearly all affected individuals exhibit cutis laxa, joint hypermobility, a wide nasal bridge, and a long philtrum. Additional features include growth delay, hypertelorism, and multiple bladder diverticula, which are consistently observed. Respiratory issues such as emphysema, tracheomalacia, and atelectasis are common, while a subset of patients may experience pyloric stenosis, feeding difficulties, and redundant skin. Other findings can include large fontanelles, inguinal and umbilical hernias, as well as facial features like retrognathia, micrognathia, and in some cases, a progeroid facial appearance. Not all individuals experience every feature, and severity varies considerably.

This condition is caused by mutations in the LTBP4 gene, which is essential for the formation and maintenance of elastic fibers in connective tissue. It is inherited in an autosomal recessive pattern, meaning that an affected individual has received one mutated copy of the gene from each parent. The condition is more common when parents share a common ancestor, as this increases the likelihood that both carry the same rare genetic variant. Genetic counseling is advised for families to understand the implications for future pregnancies.

Currently, management focuses on supportive care and symptom relief since there are no targeted therapies or FDA-approved treatments available specifically for this condition. Treatment is individualized and centers on a multidisciplinary approach, with regular surveillance by specialists to monitor respiratory, gastrointestinal, and urinary functions. Regular surveillance is an essential part of long-term care, helping to identify potential complications early. Genetic counseling is also recommended to assist families in understanding their options and inheritance risks.

Outcomes vary widely among affected individuals, with the clinical course influenced by symptom severity, age at diagnosis, and access to comprehensive care. With current standards of care, many individuals benefit from supportive and multidisciplinary management, though challenges across multiple organ systems may persist over time. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition and to engage in genetic counseling for guidance on long-term management and family planning.