EFEMP2-Related Cutis Laxa

Clinical characteristics: EFEMP2-related cutis laxa, or autosomal recessive cutis laxa type 1B (ARCL1B), is characterized by cutis laxa and systemic involvement, most commonly arterial tortuosity, aneurysms, and stenosis; retrognathia; joint laxity; and arachnodactyly. Severity ranges from perinatal lethality as a result of cardiopulmonary failure to manifestations limited to the vascular and craniofacial systems.

Diagnosis/testing: The diagnosis of EFEMP2-related cutis laxa is established in a proband with suggestive findings and biallelic pathogenic variants in EFEMP2 identified by molecular genetic testing.

Management: Treatment of manifestations: Treatment of aortic root dilatation with beta-blockers or angiotensin receptor inhibitors can be considered. Aortic aneurysm replacement has been performed successfully. Symptomatic treatment of pulmonary emphysema; muscle-reinforcing physical therapy for joint hypermobility; routine repair of hernias. Tracheostomy may be necessary when retrognathia leads to upper-airway obstruction.

Surveillance: Follow-up evaluations with a cardiologist and pulmonologist at least annually starting from the time of diagnosis. Annual MR angiography from head to pelvis.

Agents/circumstances to avoid: Sun tanning to avoid damaging the skin; cigarette smoking to avoid worsening of emphysema.

Genetic counseling: EFEMP2-related cutis laxa is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an EFEMP2 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the EFEMP2 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.