Clinical Guidance

No genotype-phenotype correlations for the major clinical signs have been reported.

Source: GeneReviews — "Lymphedema-Distichiasis Syndrome"

Penetrance

Approximately 80% of individuals with lymphedema-distichiasis syndrome have lymphedema by early adulthood (age 30 years), although a few individuals may develop lymphedema later. Approximately 94% of affected individuals have distichiasis. In all families with FOXC pathogenic variants reported, at least one individual has had distichiasis.

Source: GeneReviews — "Lymphedema-Distichiasis Syndrome"

Diagnostic Criteria

Suggestive Findings

Lymphedema-distichiasis syndrome (LDS) should be suspected in individuals with the following clinical findings:

Source: GeneReviews — "Lymphedema-Distichiasis Syndrome"

Differential Diagnosis

Table 2.

Disorders to Consider in the Differential Diagnosis of Lymphedema-Distichiasis Syndrome (LDS)

DiffDx Disorder | Gene(s) | MOI | Clinical Features of DiffDx Disorder

Overlapping w/LDS | Distinguishing from LDS

Milroy disease

| FLT4 | AD | Lymphedema1 | • Typically congenital-onset lymphedema (very rarely presents later)

• Absence of distichiasis

Meige disease(OMIM 153200) | Unknown | AD | • Absence of distichiasis

Hypotrichosis-lymphedema-telangiectasia syndrome(OMIM 607823) | SOX18 | AR | • Loss of hair

• Telangiectasia, particularly in the palms

• Absence of distichiasis

Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome(OMIM 137940) | AD

Lymphedema microcephaly(OMIM 152950) | KIF11 | AD | • Small head circumference

• May be associated w/chorioretinopathy /or ID

• Absence of distichiasis

Source: GeneReviews — "Lymphedema-Distichiasis Syndrome"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs of in an individual diagnosed with lymphedema-distichiasis syndrome (LDS), 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 Lymphedema-Distichiasis Syndrome

Source: GeneReviews — "Lymphedema-Distichiasis Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Lymphedema-Distichiasis Syndrome"

Surveillance Guidelines

Table 4. Recommended Surveillance for Individuals with Lymphedema-Distichiasis Syndrome

Source: GeneReviews — "Lymphedema-Distichiasis Syndrome"