OMIM ID:
Lymphedema-Distichiasis Syndrome
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
This form of lymphedema is associated with distichiasis, often with trichiasis and significant corneal damage in about 75% of patients. Onset of symptoms may occur at any age but usually during childhood or adolescence. Photophobia, epiphora, corneal erosions, ptosis, and partial ectropion of the lids may also be seen. The secondary symptoms of trichiasis are not always present and slit lamp examination of the lashes may be necessary to see the duplicated row of lashes. The lashes often grow out of the Meibomian orifices.
Systemic Features
Cardiac defects, cleft palate, and spinal extradural cysts occur in some families. Type II diabetes and interstitial nephritis have been reported. The lymph channels in the lower extremities may be normal or increased in number, especially below the knee where pitting edema is most often first seen, even as early as the first decade of life. Lymphedema occurs earlier in males and secondary cellulitis is a greater risk. It is usually confined to the lower extremities and is often asymmetrical. Not all patients have the complete syndrome, while lymphedema and distichiasis can be inherited as individual disorders without being associated. Males are more likely to have the complete syndrome.
Several families with this syndrome secondary to mutations in the FOXC2 have been reported to have renal anomalies ranging from kidney agenesis to malrotation.
Genetics
Inheritance
This disorder is inherited in an autosomal dominant pattern and several families have been found to have mutations in the FOXC2 gene on chromosome 16 (16q24.3). A Chinese family with an affected father and two affected offspring (one male and one female) has been reported with distichiasis but no lymphedema. A premature stop codon was found in the FOXC2 transcription gene (16q24.1) in these family members suggesting that they may have had the lymphedema-distichiasis syndrome instead.
Blatt distichiasis is a unique disorder without the lymphedema (126300).
Double rows of eyelashes are also part of the blepharocheilodontic syndrome (119580).
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission