Cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies

Cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies (also known as LTBP4-related cutis laxa or autosomal recessive cutis laxa type 1C, ARCL1C) is an extremely rare and severe inherited connective tissue disorder caused by biallelic mutations in the LTBP4 gene, which encodes latent transforming growth factor-beta binding protein 4. This protein plays a critical role in the assembly and function of elastic fibers throughout the body. The disease is characterized by generalized cutis laxa (loose, redundant, inelastic skin that hangs in folds), giving affected individuals a prematurely aged appearance. The condition profoundly affects multiple organ systems. Pulmonary involvement includes severe emphysema and pulmonary arterial hypertension, which can be life-threatening. Gastrointestinal anomalies include diverticula, intestinal tortuosity, and pyloric stenosis. Urinary tract abnormalities such as bladder diverticula, vesicoureteral reflux, and hydronephrosis are common. Additional features may include craniofacial dysmorphism, inguinal hernias, joint hypermobility, and cardiovascular anomalies including peripheral pulmonary artery stenosis and other vascular defects. Growth retardation and developmental delay may also be present. The prognosis is often poor, with many affected infants experiencing severe cardiopulmonary complications in early life. There is currently no curative treatment for this condition. Management is supportive and multidisciplinary, focusing on respiratory support, surgical correction of gastrointestinal and urinary tract anomalies, and monitoring of cardiovascular complications. Genetic counseling is recommended for affected families.

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