Lymphedema–distichiasis syndrome

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Lymphedema–distichiasis syndrome
Other namesLymphedema with distichiasis[1]
Autosomal dominant - en.svg
Lymphedema–distichiasis syndrome is inherited in an autosomal dominant manner

Lymphedema–distichiasis syndrome is a medical condition associated with the FOXC2 gene.[2]:849 People with this hereditary condition have a double row of eyelashes, which is called distichiasis, and a risk of swollen limbs due to problems in the lymphatic system.

Genetics[edit]

Lymphedema-distichiasis is inherited in an autosomal dominant fashion.[3] It is estimated that only ¼ of diagnosed individuals did not inherit the condition but rather acquired the syndrome via a de novo mutation.[4] Symptoms emerge between the life stages of puberty to early adulthood (around 30 years old).[5] This is the result of a mutation in the FOXC2 gene.[6]  FOXC2 is a transcription factor associated with developmental processes. To date, at least 70 mutations of FOXC2 have been investigated in connection with lymphedema-distichiasis patients. These mutations are thought to be both loss of function and gain of function mutations.[5] For some time, FOXC2 mutations were thought to be associated with lymphedema-distichiasis as a combined condition. However, there are now cases that indicate that FOXC2 mutations can cause distichiasis in humans without lymphedema.[5]

Mutations[edit]

The A3G mutation is a pathogenic mutation (located in the AD-1 region of the FOXC2 protein) that lowers FOXC2’s ability to turn on target genes.[5]

p.Y41F, a missense mutation, is also located in FOXC2 AD-1. p.Y41F is one of eleven mutations found in the FOXC2 gene. It was determined that of these 11 mutations, one was nonsense, six were missense, and four were frameshift mutations.[7]

It is hypothesized that gain of function mutations lead to hypoplasia and loss of function mutations lead to hyperplasia specifically in individuals with lymphedema.[5]

Symptoms[edit]

The main symptoms of lymphedema-distichiasis are limb swelling and a double row of eyelashes. Symptoms that have been noted in some but not all cases include cysts, light sensitivity, cardiac defects, cleft palate, and eye problems such as astigmatism and cornea scarring.[6]

Syndrome Diagnosis and Management[edit]

Currently, the most accurate test to determine if an individual is affected by lymphedema-distichiasis syndrome is done via Sanger sequencing, which includes whole genome analysis and single gene and multigene testing.[3][8] Sequenced DNA that exhibits mutations in the FOXC2 gene are considered confirmed clinical diagnoses. In addition to Sanger sequencing, Multiplex Ligation Probe Amplification (MLPA) can be used to determine if  duplications and deletions in  FOXC2 are present in an individual, making it a practical testing mechanism.[3] Lastly, diagnosis is sometimes determined without genome testing. If an individual exhibits multiple symptoms of lymphedema-distichiasis and has a medical history consistent with known lymphedema-distichiasis symptoms, then their diagnosis is confirmed via clinical evaluation.[9]

Lymphedema-distichiasis is a rare genetic disease, it is unknown how many individuals are affected and what the frequency of the condition is.[10] As a result, there are few syndrome management techniques: Symptoms of distichiasis can be minimized via eyelash plucking, electrolysis and other various treatments.[8] Limb swelling can be reduced using compression clothing and bandages. Lastly, rapid treatment of broken skin and cellulitis lessens severity of symptoms.[8]

See also[edit]

Notes[edit]

  1. ^ "Lymphedema-distichiasis syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 21 April 2019.
  2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6.
  3. ^ a b c Rakhmanov, Yeltay; Maltese, Paolo Enrico; Paolacci, Stefano; Marinelli, Carla; Bertelli, Matteo (2018-09-01). "Genetic testing for lymphedema-distichiasis syndrome". The EuroBiotech Journal. 2 (s1): 13–15. doi:10.2478/ebtj-2018-0026. ISSN 2564-615X.
  4. ^ Kolin, Talia (1991-07-01). "Hereditary Lymphedema and Distichiasis". Archives of Ophthalmology. 109 (7): 980. doi:10.1001/archopht.1991.01080070092042. ISSN 0003-9950. PMC 6693661. PMID 2064580.
  5. ^ a b c d e Tavian, D (2016). "FOXC2 disease-mutations identified in lymphedema-distichiasis patients cause both loss and gain of protein function". Oncotarget. 7 (34): 54228–54239. doi:10.18632/oncotarget.9797. PMID 27276711.
  6. ^ a b Fang, Jianming; Dagenais, Susan L.; Erickson, Robert P.; Arlt, Martin F.; Glynn, Michael W.; Gorski, Jerome L.; Seaver, Laurie H.; Glover, Thomas W. (December 2000). "Mutations in FOXC2 (MFH-1), a Forkhead Family Transcription Factor, Are Responsible for the Hereditary Lymphedema-Distichiasis Syndrome". The American Journal of Human Genetics. 67 (6): 1382–1388. doi:10.1086/316915. ISSN 0002-9297. PMC 1287915. PMID 11078474.
  7. ^ van Steensel, M.A.M.; Damstra, R.J.; Heitink, M.; Bladergroen, R.S.; Veraart, J.; Steijlen, Peter M.; van Geel, M. (December 2009). "Novel missense mutations in theFOXC2gene alter transcriptional activity". Human Mutation. 30 (12): E1002–E1009. doi:10.1002/humu.21127. ISSN 1059-7794. PMID 19760751.
  8. ^ a b c Mansour, Sahar; Brice, Glen W.; Jeffery, Steve; Mortimer, Peter (1993), Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E. (eds.), "Lymphedema-Distichiasis Syndrome", GeneReviews®, University of Washington, Seattle, PMID 20301630, retrieved 2020-04-15
  9. ^ "Lymphedema-Distichiasis Syndrome". NORD (National Organization for Rare Disorders). Retrieved 2020-04-15.
  10. ^ Reference, Genetics Home. "Lymphedema-distichiasis syndrome". Genetics Home Reference. Retrieved 2020-04-15.

References[edit]

External links[edit]

Classification
External resources