Lymphedema-Distichiasis Syndrome

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

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).

Treatment
Treatment Options: 

Electrolysis of individual misdirected lashes can be applied.  Prompt treatment of lid cellulitis is important. Surgical repair of scarred lid tissue can restore cosmesis lid function and improve cosmesis.

References
Article Title: 

Renal anomalies and lymphedema distichiasis syndrome

Jones GE, Richmond AK, Navti O, Mousa HA, Abbs S, Thompson E, Mansour S, Vasudevan PC. Renal anomalies and lymphedema distichiasis syndrome. A rare association? Am J Med Genet A. 2017 May;173(8):2251-2256.

PubMed ID: 
28544699

Hereditary lymphedema and distichiasis

Kolin T, Johns KJ, Wadlington WB, Butler MG, Sunalp MA, Wright KW. Hereditary lymphedema and distichiasis. Arch Ophthalmol. 1991 Jul;109(7):980-1.

PubMed ID: 
2064580

References

Sheth T, Attzs M, Tambe K. A new perspective in oculoplastic surgical management of symptomatic distichiasis in lymphedema-distichiasis syndrome. Orbit. 2018 Dec 5:1-4. doi: 10.1080/01676830.2018.1546749. [Epub ahead of print].

PubMedID: 30516410

Jones GE, Richmond AK, Navti O, Mousa HA, Abbs S, Thompson E, Mansour S, Vasudevan PC. Renal anomalies and lymphedema distichiasis syndrome. A rare association? Am J Med Genet A. 2017 May;173(8):2251-2256.

PubMedID: 28544699

Zhang L, He J, Han B, Lu L, Fan J, Zhang H, Ge S, Zhou Y, Jia R, Fan X. Novel FOXC2 Mutation in Hereditary Distichiasis Impairs DNA-Binding Activity and Transcriptional Activation. Int J Biol Sci. 2016 Aug 6;12(9):1114-20.

PubMedID: 27570485

Ogura Y, Yabuki S, Iida A, Kou I, Nakajima M, Kano H, Shiina M, Kikuchi S, Toyama Y, Ogata K, Nakamura M, Matsumoto M, Ikegawa S. FOXC2 Mutations in Familial and Sporadic Spinal Extradural Arachnoid Cyst. PLoS One. 2013 Nov 22;8(11):e80548.

PubMedID: 24278289

Itoh M, Nakagawa H. A novel complex insertion-deletion mutation in the FOXC2 gene in a Japanese patient with Lymphedema-Distichiasis Syndrome. Eur J Dermatol. 2013 Jun 7. [Epub ahead of print].

PubMedID: 23747797

Sutkowska E, Gil J, Stembalska A, Hill-Bator A, Szuba A. Novel mutation in the FOXC2 gene in three generations of a family with lymphoedema-distichiasis syndrome. Gene. 2012 Feb 14. [Epub ahead of print] PubMed PMID: 22349027.

PubMedID: 22349027

Brice G, Mansour S, Bell R, Collin JR, Child AH, Brady AF, Sarfarazi M, Burnand KG, Jeffery S, Mortimer P, Murday VA. Analysis of the phenotypic abnormalities in lymphoedema-distichiasis syndrome in 74 patients with FOXC2 mutations or linkage to 16q24. J Med Genet. 2002 Jul;39(7):478-83.

PubMedID: 12114478

Kolin T, Johns KJ, Wadlington WB, Butler MG, Sunalp MA, Wright KW. Hereditary lymphedema and distichiasis. Arch Ophthalmol. 1991 Jul;109(7):980-1.

PubMedID: 2064580