MCID: LYM029
MIFTS: 41

Lymphedema-Distichiasis Syndrome

Categories: Genetic diseases, Rare diseases, Nephrological diseases, Immune diseases

Aliases & Classifications for Lymphedema-Distichiasis Syndrome

MalaCards integrated aliases for Lymphedema-Distichiasis Syndrome:

Name: Lymphedema-Distichiasis Syndrome 53 23 49 24 71 51
Lymphedema with Distichiasis 53 23 49 24 71
Lymphedema-Distichiasis Syndrome with Renal Disease and Diabetes Mellitus 53 28 13
Distichiasis-Lymphedema Syndrome 24 28
Hereditary Lymphedema-Distichiasis Syndrome 49
Lymphedema Distichiasis Syndrome 69
Lymphedema Distichiasis 72
Lymphedema-Distichiasis 71
Lyd 71

Characteristics:

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
onset of lymphedema around puberty
onset occurs earlier in males than females
allelic disorders with overlapping phenotypes include hereditary lymphedema type ii , lymphedema and ptosis , and yellow nail and lymphedema syndrome


HPO:

31
lymphedema-distichiasis syndrome:
Inheritance autosomal dominant inheritance


GeneReviews:

23
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...

Classifications:



Summaries for Lymphedema-Distichiasis Syndrome

Genetics Home Reference : 24 Lymphedema-distichiasis syndrome is a condition that affects the normal function of the lymphatic system, which is a part of the circulatory and immune systems. The lymphatic system produces and transports fluids and immune cells throughout the body. People with lymphedema-distichiasis syndrome develop puffiness or swelling (lymphedema) of the limbs, typically the legs and feet. Another characteristic of this syndrome is the growth of extra eyelashes (distichiasis), ranging from a few extra eyelashes to a full extra set on both the upper and lower lids. These eyelashes do not grow along the edge of the eyelid, but out of its inner lining. When the abnormal eyelashes touch the eyeball, they can cause damage to the clear covering of the eye (cornea). Related eye problems can include an irregular curvature of the cornea causing blurred vision (astigmatism) or scarring of the cornea. Other health problems associated with this disorder include swollen and knotted (varicose) veins, droopy eyelids (ptosis), heart abnormalities, and an opening in the roof of the mouth (a cleft palate).

MalaCards based summary : Lymphedema-Distichiasis Syndrome, also known as lymphedema with distichiasis, is related to distichiasis and hereditary lymphedema, and has symptoms including photophobia, muscle weakness and ptosis. An important gene associated with Lymphedema-Distichiasis Syndrome is FOXC2 (Forkhead Box C2). Affiliated tissues include eye, heart and skin, and related phenotypes are Increased shRNA abundance (Z-score > 2) and Increased shRNA abundance (Z-score > 2)

OMIM : 53 Lymphedema-distichiasis is an autosomal dominant disorder that classically presents as lymphedema of the limbs and double rows of eyelashes (distichiasis). Irritation of the cornea, with corneal ulceration in some cases, brings the patients to the attention of ophthalmologists. Other complications may include cardiac defects, varicose veins, ptosis, cleft palate, spinal extradural cysts, and photophobia (Fang et al., 2000; Brice et al., 2002). (153400)

UniProtKB/Swiss-Prot : 71 Lymphedema-distichiasis: A disorder characterized by primary limb lymphedema associated with distichiasis (double rows of eyelashes, with extra eyelashes growing from the Meibomian gland orifices). Swelling of the extremities, due to altered lymphatic flow, usually appears in late childhood or puberty. Most affected individuals have ocular findings including corneal irritation, recurrent conjunctivitis, and photophobia. Drooping of the upper eyelid (ptosis) is a variable feature of the lymphedema-distichiasis syndrome, occurring in about 30% of patients.

NIH Rare Diseases : 49 Lymphedema distichiasis syndrome is a condition that affects the normal function of the lymphatic system (part of the immune system that produces and transports fluids and immune cells throughout the body). People with this condition are born with extra eyelashes (distichiasis) and develop puffiness or swelling (lymphedema) of the limbs by the time they are in their forties. The abnormal eyelashes, which grow along the inner lining of the eyelid, often touch the eyeball and can cause damage to the clear covering of the eye (cornea). Other eye problems such as an irregular curvature of the cornea causing blurred vision (astigmatism) or scarring of the cornea may also occur. Other health problems, varicose veins, droopy eyelids (ptosis), heart abnormalities, and an opening in the roof of the mouth (a cleft palate), may also be present. Lymphedema-distichiasis syndrome is caused by mutations in the FOXC2 gene. This condition is inherited in an autosomal dominant pattern. Last updated: 4/1/2011

Wikipedia : 72 Lymphedema–distichiasis syndrome is a medical condition associated with the FOXC2... more...

GeneReviews: NBK1457

Related Diseases for Lymphedema-Distichiasis Syndrome

Diseases related to Lymphedema-Distichiasis Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 distichiasis 29.8 FOXC2 FOXL1 FOXP2
2 hereditary lymphedema 29.5 FOXC2 FOXL1
3 lymphedema 10.7
4 diabetes mellitus 10.1
5 arachnoiditis 10.1
6 arachnoid cysts 10.1
7 hypoplastic left heart syndrome 9.3 FOXC2 FOXL1

Graphical network of the top 20 diseases related to Lymphedema-Distichiasis Syndrome:



Diseases related to Lymphedema-Distichiasis Syndrome

Symptoms & Phenotypes for Lymphedema-Distichiasis Syndrome

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Eyes:
photophobia
ptosis
conjunctivitis
corneal ulceration
accessory eyelashes
more
Cardiovascular Heart:
tetralogy of fallot
congenital heart defects (7%)
ventricular septal defects
arrhythmias

Head And Neck Mouth:
cleft lip (4%)
cleft palate (4%)

Cardiovascular Vascular:
patent ductus arteriosus
varicose veins

Muscle Soft Tissue:
lymphedema, predominantly in the lower limbs
cellulitis or infection may occur
lymphography shows increased number of dilated lymphatic vessels (hyperplasia)

Skeletal Spine:
spinal extradural cysts may occur


Clinical features from OMIM:

153400

Human phenotypes related to Lymphedema-Distichiasis Syndrome:

31 (show all 31)
# Description HPO Frequency HPO Source Accession
1 photophobia 31 hallmark (90%) HP:0000613
2 muscle weakness 31 frequent (33%) HP:0001324
3 ptosis 31 frequent (33%) HP:0000508
4 diabetes mellitus 31 occasional (7.5%) HP:0000819
5 cataract 31 frequent (33%) HP:0000518
6 proteinuria 31 occasional (7.5%) HP:0000093
7 arrhythmia 31 occasional (7.5%) HP:0011675
8 cleft palate 31 very rare (1%) HP:0000175
9 patent ductus arteriosus 31 occasional (7.5%) HP:0001643
10 corneal erosion 31 hallmark (90%) HP:0200020
11 lymphedema 31 HP:0001004
12 webbed neck 31 occasional (7.5%) HP:0000465
13 glomerulopathy 31 occasional (7.5%) HP:0100820
14 abnormality of the musculature 31 HP:0003011
15 tetralogy of fallot 31 HP:0001636
16 ventricular septal defect 31 HP:0001629
17 varicose veins 31 frequent (33%) HP:0002619
18 conjunctivitis 31 hallmark (90%) HP:0000509
19 recurrent urinary tract infections 31 occasional (7.5%) HP:0000010
20 renal duplication 31 occasional (7.5%) HP:0000075
21 cleft upper lip 31 very rare (1%) HP:0000204
22 distichiasis 31 hallmark (90%) HP:0009743
23 ectropion 31 frequent (33%) HP:0000656
24 recurrent skin infections 31 occasional (7.5%) HP:0001581
25 tubulointerstitial nephritis 31 occasional (7.5%) HP:0001970
26 abnormality of the pulmonary vasculature 31 occasional (7.5%) HP:0004930
27 predominantly lower limb lymphedema 31 hallmark (90%) HP:0003550
28 spinalarachnoid cyst 31 occasional (7.5%) HP:0009745
29 fibrosarcoma 31 occasional (7.5%) HP:0100244
30 corneal ulceration 31 HP:0012804
31 recurrent corneal erosions 31 HP:0000495

UMLS symptoms related to Lymphedema-Distichiasis Syndrome:


photophobia

GenomeRNAi Phenotypes related to Lymphedema-Distichiasis Syndrome according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-123 9.28 FOXP2
2 Increased shRNA abundance (Z-score > 2) GR00366-A-152 9.28 FOXL1
3 Increased shRNA abundance (Z-score > 2) GR00366-A-166 9.28 FOXL1
4 Increased shRNA abundance (Z-score > 2) GR00366-A-176 9.28 FOXL1 FOXP2
5 Increased shRNA abundance (Z-score > 2) GR00366-A-50 9.28 FOXP2
6 Increased shRNA abundance (Z-score > 2) GR00366-A-57 9.28 FOXL1
7 Increased shRNA abundance (Z-score > 2) GR00366-A-76 9.28 FOXP2
8 Increased shRNA abundance (Z-score > 2) GR00366-A-88 9.28 FOXL1

Drugs & Therapeutics for Lymphedema-Distichiasis Syndrome

Search Clinical Trials , NIH Clinical Center for Lymphedema-Distichiasis Syndrome

Genetic Tests for Lymphedema-Distichiasis Syndrome

Genetic tests related to Lymphedema-Distichiasis Syndrome:

# Genetic test Affiliating Genes
1 Distichiasis-Lymphedema Syndrome 28 FOXC2
2 Lymphedema-Distichiasis Syndrome with Renal Disease and Diabetes Mellitus 28

Anatomical Context for Lymphedema-Distichiasis Syndrome

MalaCards organs/tissues related to Lymphedema-Distichiasis Syndrome:

38
Eye, Heart, Skin

Publications for Lymphedema-Distichiasis Syndrome

Articles related to Lymphedema-Distichiasis Syndrome:

(show all 23)
# Title Authors Year
1
Novel FOXC2 Mutation and Distichiasis in a Patient With Lymphedema-Distichiasis Syndrome. ( 29406328 )
2018
2
Lymphedema-Distichiasis Syndrome in a Male Patient Followed for 16 Years. ( 29342028 )
2018
3
Renal anomalies and lymphedema distichiasis syndrome. A rare association? ( 28544699 )
2017
4
Early Mandibular Distraction to Relieve Robin Severe Airway Obstruction in Two Siblings with Lymphedema-Distichiasis Syndrome. ( 27752211 )
2016
5
Integration-free T cell-derived human induced pluripotent stem cells (iPSCs) from a patient with lymphedema-distichiasis syndrome (LDS) carrying an insertion-deletion complex mutation in the FOXC2 gene. ( 27346194 )
2016
6
Lymphedema-distichiasis syndrome. ( 26124227 )
2015
7
A novel complex insertion-deletion mutation in the FOXC2 gene in a Japanese patient with Lymphedema-Distichiasis Syndrome. ( 23747797 )
2013
8
A case of lymphedema-distichiasis syndrome carrying a new de novo frameshift FOXC2 mutation. ( 20450314 )
2010
9
Rare association of immunoglobulin A nephropathy and lymphedema-distichiasis syndrome. ( 20124880 )
2010
10
Spinal extradural arachnoid cysts in lymphedema-distichiasis syndrome. ( 20535019 )
2010
11
A novel missense mutation and two microrearrangements in the FOXC2 gene of three families with lymphedema-distichiasis syndrome. ( 20552815 )
2010
12
Lymphedema-distichiasis syndrome without FOXC2 mutation: evidence for chromosome 16 duplication upstream of FOXC2. ( 20218083 )
2009
13
Novel FOXC2 missense mutation identified in patient with lymphedema-distichiasis syndrome and review. ( 19013876 )
2008
14
Lymphedema-distichiasis syndrome: a distinct type of primary lymphedema caused by mutations in the FOXC2 gene. ( 18986489 )
2008
15
Perinatal diagnosis of a lymphedema-distichiasis syndrome (LD). ( 17721865 )
2007
16
Foxc2 is expressed in developing lymphatic vessels and other tissues associated with lymphedema-distichiasis syndrome. ( 15465483 )
2004
17
A novel frameshift mutation of FOXC2 gene in a family with hereditary lymphedema-distichiasis syndrome associated with renal disease and diabetes mellitus. ( 15523639 )
2004
18
FOXC2 haploinsufficient mice are a model for human autosomal dominant lymphedema-distichiasis syndrome. ( 12719382 )
2003
19
Literature watch. FOXC2 haploinsufficient mice are a model for human autosomal dominant lymphedema-distichiasis syndrome. ( 15624441 )
2003
20
Lymphedema-distichiasis syndrome and FOXC2 gene mutation. ( 12383817 )
2002
21
Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome. ( 11078474 )
2000
22
Lymphedema-distichiasis syndrome: report of a case and review. ( 10086462 )
1999
23
Lymphedema-Distichiasis Syndrome ( 20301630 )
1993

Variations for Lymphedema-Distichiasis Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Lymphedema-Distichiasis Syndrome:

71
# Symbol AA change Variation ID SNP ID
1 FOXC2 p.Ser125Leu VAR_018418 rs121909106

ClinVar genetic disease variations for Lymphedema-Distichiasis Syndrome:

6 (show all 13)
# Gene Variation Type Significance SNP ID Assembly Location
1 FOXC2 NM_005251.2(FOXC2): c.297C> G (p.Tyr99Ter) single nucleotide variant Pathogenic rs104894516 GRCh37 Chromosome 16, 86601238: 86601238
2 FOXC2 FOXC2, 4-BP DUP, NT1093 duplication Pathogenic
3 FOXC2 FOXC2, 11-BP DEL, NT290 deletion Pathogenic
4 FOXC2 FOXC2, 1-BP DEL, 1331A deletion Pathogenic
5 FOXC2 FOXC2, 1-BP INS, 209T insertion Pathogenic
6 FOXC2 FOXC2, 2-BP INS, 201CT insertion Pathogenic
7 FOXC2 FOXC2, 1-BP INS, 589C insertion Pathogenic
8 FOXC2 FOXC2, 1-BP DEL, 505A deletion Pathogenic
9 FOXC2 FOXC2, 8-BP DEL, NT914 deletion Pathogenic
10 FOXC2 FOXC2, 1-BP INS, 1006A insertion Pathogenic
11 FOXC2 FOXC2, 5-BP INS/79-BP DEL, NT602 indel Pathogenic
12 FOXC2 NM_005251.2(FOXC2): c.374C> T (p.Ser125Leu) single nucleotide variant Pathogenic rs121909106 GRCh37 Chromosome 16, 86601315: 86601315
13 FOXC2 NM_005251.2(FOXC2): c.362G> A (p.Arg121His) single nucleotide variant Pathogenic rs121909107 GRCh37 Chromosome 16, 86601303: 86601303

Expression for Lymphedema-Distichiasis Syndrome

Search GEO for disease gene expression data for Lymphedema-Distichiasis Syndrome.

Pathways for Lymphedema-Distichiasis Syndrome

GO Terms for Lymphedema-Distichiasis Syndrome

Biological processes related to Lymphedema-Distichiasis Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of transcription, DNA-templated GO:0006355 9.54 FOXC2 FOXL1 FOXP2
2 transcription, DNA-templated GO:0006351 9.5 FOXC2 FOXL1 FOXP2
3 heart development GO:0007507 9.26 FOXC2 FOXL1
4 anatomical structure morphogenesis GO:0009653 9.16 FOXL1 FOXP2
5 cell differentiation GO:0030154 9.13 FOXC2 FOXL1 FOXP2
6 camera-type eye development GO:0043010 8.62 FOXC2 FOXP2

Molecular functions related to Lymphedema-Distichiasis Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA binding GO:0003677 9.43 FOXC2 FOXL1 FOXP2
2 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0000981 9.16 FOXL1 FOXP2
3 DNA binding transcription factor activity GO:0003700 9.13 FOXC2 FOXL1 FOXP2
4 sequence-specific DNA binding GO:0043565 8.8 FOXC2 FOXL1 FOXP2

Sources for Lymphedema-Distichiasis Syndrome

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10 dbSNP
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70 UMLS via Orphanet
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