Diagnostic Criteria

No formal clinical diagnostic criteria have been established for LTBP4-related cutis laxa.

Suggestive Findings

LTBP4-related cutis laxa should be suspected in individuals with the following clinical and family history findings.

Clinical findings

• Loose redundant skin folds (cutis laxa)

• Pulmonary emphysema

• Gastrointestinal and/or urinary tract diverticula

Family history is consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.

Establishing the Diagnosis

The diagnosis of LTBP4-related cutis laxa is established in a proband with cutis laxa and biallelic pathogenic (or likely pathogenic) variants in LTBP4 identified by molecular genetic testing . Note: (1) Per American College of Medical Ge...

Source: GeneReviews — "LTBP4-Related Cutis Laxa"

Differential Diagnosis

The primary clinical differential diagnoses to consider are autosomal recessive cutis laxa type 1A (ARCL1A), autosomal recessive cutis laxa type 1B (ARCL1B), and autosomal dominant cutis laxa type 1 (ADCL1): • ARCL1A (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 tissue disorder such as inguinal hernias and hollow visceral diverticula (e.g., intestine, bladder). Occasionally, supravalvular aortic stenosis is observed. Considerable overlap exists between FBLN5- and LTBP4-related cutis laxa and the two entities are difficult to distinguish from each other purely on a clinical basis. In FBLN5-related cutis laxa, the skin features may be more pronounced. In LTBP-related cutis laxa, supravalvular aortic stenosis has not yet been observed, while bladder and gastrointestinal diverticula as well as rectal prolapse are more frequent. • 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. The severe arterial tortuosity seen in EFEMP2-related cutis laxa is absent in LTBP4-related cutis laxa. • ADCL1 (ELN-related cutis laxa) presents with generalized cutis laxa of variable severity. Aortic root dilatation and emphysema may occur as early as childhood and are progressive. However, emphysema is usually milder than in LTBP4-related cutis laxa . ARCL1A, ARCL1B, ADCL1 and other disorders to consider in the differential diagnosis of LTBP4-related cutis laxa are summarized in . Table 3. Disorders to Consider in the Differential Diagnosis of LTBP4-Related Cutis Laxa

Management Guidelines

No clinical practice guidelines for LTBP4-related cutis laxa have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with LTBP4-related cutis laxa, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with LTBP4-Related Cutis Laxa

Source: GeneReviews — "LTBP4-Related Cutis Laxa"

Surveillance Guidelines

Table 6. Recommended Surveillance for Individuals with LTBP4-Related Cutis Laxa

Source: GeneReviews — "LTBP4-Related Cutis Laxa"