Diagnostic Criteria

Suggestive Findings

FBLN5-related cutis laxa should be suspected in individuals with the following clinical features:

• Cutis laxa

• Pulmonary emphysema

• Arterial involvement (e.g., peripheral pulmonary artery stenosis, supravalvar aortic stenosis)

• Inguinal hernias

• Hollow viscus diverticula (e.g., intestine, bladder)

• Pyloric stenosis

Establishing the Diagnosis

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

Source: GeneReviews — "FBLN5-Related Cutis Laxa"

Differential Diagnosis

Other disorders characterized by cutis laxa are summarized in . EFEMP2-related cutis laxa (ARCL1B). EFEMP2-related cutis laxa 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. The cutis laxa and emphysema are similar in FBLN4- or FBLN5-related cutis laxa; however, to date, the diaphragmatic changes and arterial aneurysms seem more predominant in EFEMP2-related cutis laxa. ATP6V0A2-related cutis laxa (ARCL2A) spans a phenotypic spectrum that includes Debr-type cutis laxa at the severe end and wrinkly skin syndrome at the mild end.

Source: GeneReviews — "FBLN5-Related Cutis Laxa"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with FBLN5-related cutis laxa, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with FBLN5-Related Cutis Laxa

Source: GeneReviews — "FBLN5-Related Cutis Laxa"

Surveillance Guidelines

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

Source: GeneReviews — "FBLN5-Related Cutis Laxa"