ELN-Related Cutis Laxa

Excerpt

Clinical characteristics: ELN-related cutis laxa is characterized by generalized cutis laxa (ranging from generalized skin redundancy causing excessive skin folds to skin hyperextensibility without obvious skin folds) and distinctive facial features that may become more prominent with age. Other common findings are joint hyperlaxity in infancy and increasing risk of inguinal hernia at all ages. Progressive findings that may be present as early as childhood include ptosis, aortic root dilatation, and emphysema.

Diagnosis/testing: The diagnosis of ELN-related cutis laxa is established in a proband with suggestive findings and a heterozygous pathogenic (or likely pathogenic) variant in ELN identified by molecular genetic testing.

Management: Treatment of manifestations: There is no cure for ELN-related cutis laxa. Experience in treating individuals with ELN-related cutis laxa is very limited. Supportive care to improve quality of life, maximize function, and reduce complications is recommended and ideally involves multidisciplinary care by specialists in general surgery, cardiothoracic surgery, cardiology, pulmonology, urology, physical therapy, ophthalmology, and medical genetics.

Surveillance: Monitor for known problems (e.g., inguinal hernias, joint hypermobility and pain) and new issues that may require interventions (e.g., ptosis, aortic root dilatation, emphysema, bladder diverticula).

Agents/circumstances to avoid: Positive pressure ventilation unless needed for life-threatening conditions; contact with people with respiratory infections; tobacco smoking; isometric exercise (which causes an increase in blood pressure); contact sports or activities that increase the risk for blunt abdominal trauma and/or joint injury or pain; sunbathing or tanning in order to preserve residual skin elasticity.

Pregnancy management: Perinatal complications for mothers with ELN-related cutis laxa or affected neonates have not been reported to date. Nonetheless, recommended evaluations for women with ELN-related cutis laxa before conception and during pregnancy are pulmonary function testing and cardiovascular assessment (including aortic root diameter). Continued cardiac surveillance for six months post partum is also recommended. Additionally, women taking a beta-blocker should continue it during pregnancy; however, some other classes of medications, such as angiotensin receptor-blocking agents, are teratogenic and should be discontinued or changed to beta-blocking agents, given the increased risk for teratogenicity typically related to second- and third-trimester exposure.

Genetic counseling: ELN-related cutis laxa is inherited in an autosomal dominant manner. About one third of individuals diagnosed with ELN-related cutis laxa have an affected parent; about two thirds of affected individuals have the disorder as the result of a de novo ELN pathogenic variant. Each child of an individual with ELN-related cutis laxa has a 50% chance of inheriting the pathogenic variant. Once the ELN pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.