FBLN5-Related Cutis Laxa

Clinical characteristics: FBLN5-related cutis laxa is characterized by cutis laxa, early childhood-onset pulmonary emphysema, peripheral pulmonary artery stenosis, and other evidence of a generalized connective disorder such as inguinal hernias and hollow viscus diverticula (e.g., intestine, bladder). Occasionally, supravalvar aortic stenosis is observed. Intrafamilial variability in age of onset is observed. Cardiorespiratory failure from complications of pulmonary emphysema (respiratory or cardiac insufficiency) is the most common cause of death.

Diagnosis/testing: The diagnosis of FBLN5-related cutis laxa is established in a proband with the characteristic clinical features and biallelic pathogenic variants in FBLN5 (autosomal recessive FBLN5-related cutis laxa) or a heterozygous pathogenic variant in FBLN5 (autosomal dominant FBLN5-related cutis laxa) identified by molecular genetic testing.

Management: Treatment of manifestations: Symptomatic treatment of pulmonary emphysema; antibiotics for urinary tract infections; routine repair of inguinal hernias; repeat plastic surgery of the face and trunk as needed.

Prevention of secondary complications: Attention to respiratory function prior to surgery; prophylactic antibiotics as needed for vesicoureteral reflux; immunizations against respiratory viruses.

Surveillance: Routine surveillance of the urinary tract for evidence of bladder diverticula and/or vesicoureteral reflux.

Agents/circumstances to avoid: Smoking; positive pressure ventilation unless needed to treat life-threatening conditions; isometric exercise and contact sports or activities that increase the risk for blunt abdominal trauma and/or joint injury or pain; exposure to respiratory infections.

Genetic counseling: FBLN5-related cutis laxa can be inherited in an autosomal recessive or (less commonly) autosomal dominant manner.

1. Autosomal recessive inheritance. At conception, each sib of an affected individual has 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.

2. Autosomal dominant inheritance. Each child of an individual with autosomal dominant cutis laxa has a 50% chance of inheriting the pathogenic variant.

Prenatal testing is possible for a pregnancy at increased risk in families in which the pathogenic variant(s) have been identified.