MCID: LYM029
MIFTS: 41

Lymphedema-Distichiasis Syndrome

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

Aliases & Classifications for Lymphedema-Distichiasis Syndrome

MalaCards integrated aliases for Lymphedema-Distichiasis Syndrome:

Name: Lymphedema-Distichiasis Syndrome 57 24 53 25 75 55
Lymphedema with Distichiasis 57 24 53 25 75
Lymphedema-Distichiasis Syndrome with Renal Disease and Diabetes Mellitus 57 29 13 6
Distichiasis-Lymphedema Syndrome 25 29 6
Hereditary Lymphedema-Distichiasis Syndrome 53
Syndrome, Lymphedema-Distichiasis 40
Lymphedema Distichiasis Syndrome 73
Lymphedema Distichiasis 76
Lymphedema-Distichiasis 75
Lyd 75

Characteristics:

OMIM:

57
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:

32
lymphedema-distichiasis syndrome:
Inheritance autosomal dominant inheritance


GeneReviews:

24
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

NIH Rare Diseases : 53 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 syndrome have extra eyelashes (distichiasis) and develop puffiness or swelling (lymphedema) of the limbs, most often the legs and feet. 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 that may occur in lymphedema-distichiasis syndrome include varicose veins, droopy eyelids (ptosis), heart abnormalities, and an opening in the roof of the mouth (cleft palate).  Lymphedema-distichiasis syndrome is caused by changes (referred to as mutations or pathogenic variants) in the FOXC2 gene. It is inherited in an autosomal dominant pattern. Diagnosis of this syndrome is based on a thorough clinical examination, detailed patient history, and identification of the symptoms mentioned above. Clinical genetic testing can be used to confirm the diagnosis. Treatment is directed at the specific symptoms present in each case. This may include complete decongestive therapy, a comprehensive management technique used to treat lympedema and/or lubrication and removal of the extra eyelashes via plucking, cryotherapy, or electrolysis.

MalaCards based summary : Lymphedema-Distichiasis Syndrome, also known as lymphedema with distichiasis, is related to distichiasis and hereditary lymphedema, and has symptoms including photophobia An important gene associated with Lymphedema-Distichiasis Syndrome is FOXC2 (Forkhead Box C2). Affiliated tissues include eye, heart and testes, and related phenotypes are cleft palate and cleft upper lip

OMIM : 57 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 : 75 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.

Genetics Home Reference : 25 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).

Wikipedia : 76 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 29.0 FOXC2 FOXL1 FOXP2
2 hereditary lymphedema 29.0 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 8.9 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:

57
Head And Neck Eyes:
ptosis
photophobia
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:

32 (show all 31)
# Description HPO Frequency HPO Source Accession
1 cleft palate 32 very rare (1%) HP:0000175
2 cleft upper lip 32 very rare (1%) HP:0000204
3 recurrent corneal erosions 32 HP:0000495
4 ptosis 32 frequent (33%) HP:0000508
5 conjunctivitis 32 hallmark (90%) HP:0000509
6 photophobia 32 hallmark (90%) HP:0000613
7 lymphedema 32 HP:0001004
8 ventricular septal defect 32 HP:0001629
9 tetralogy of fallot 32 HP:0001636
10 patent ductus arteriosus 32 occasional (7.5%) HP:0001643
11 varicose veins 32 frequent (33%) HP:0002619
12 abnormality of the musculature 32 HP:0003011
13 predominantly lower limb lymphedema 32 hallmark (90%) HP:0003550
14 distichiasis 32 hallmark (90%) HP:0009743
15 arrhythmia 32 occasional (7.5%) HP:0011675
16 corneal ulceration 32 HP:0012804
17 recurrent urinary tract infections 32 occasional (7.5%) HP:0000010
18 renal duplication 32 occasional (7.5%) HP:0000075
19 proteinuria 32 occasional (7.5%) HP:0000093
20 webbed neck 32 occasional (7.5%) HP:0000465
21 cataract 32 frequent (33%) HP:0000518
22 ectropion 32 frequent (33%) HP:0000656
23 diabetes mellitus 32 occasional (7.5%) HP:0000819
24 muscle weakness 32 frequent (33%) HP:0001324
25 recurrent skin infections 32 occasional (7.5%) HP:0001581
26 tubulointerstitial nephritis 32 occasional (7.5%) HP:0001970
27 abnormality of the pulmonary vasculature 32 occasional (7.5%) HP:0004930
28 spinalarachnoid cyst 32 occasional (7.5%) HP:0009745
29 fibrosarcoma 32 occasional (7.5%) HP:0100244
30 glomerulopathy 32 occasional (7.5%) HP:0100820
31 corneal erosion 32 hallmark (90%) HP:0200020

UMLS symptoms related to Lymphedema-Distichiasis Syndrome:


photophobia

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

26
# 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 29 FOXC2
2 Lymphedema-Distichiasis Syndrome with Renal Disease and Diabetes Mellitus 29

Anatomical Context for Lymphedema-Distichiasis Syndrome

MalaCards organs/tissues related to Lymphedema-Distichiasis Syndrome:

41
Eye, Heart, Testes, Skin

Publications for Lymphedema-Distichiasis Syndrome

Articles related to Lymphedema-Distichiasis Syndrome:

(show all 23)
# Title Authors Year
1
Lymphedema-Distichiasis Syndrome in a Male Patient Followed for 16 Years. ( 29342028 )
2018
2
Novel FOXC2 Mutation and Distichiasis in a Patient With Lymphedema-Distichiasis Syndrome. ( 29406328 )
2018
3
Renal anomalies and lymphedema distichiasis syndrome. A rare association? ( 28544699 )
2017
4
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
5
Early Mandibular Distraction to Relieve Robin Severe Airway Obstruction in Two Siblings with Lymphedema-Distichiasis Syndrome. ( 27752211 )
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 novel missense mutation and two microrearrangements in the FOXC2 gene of three families with lymphedema-distichiasis syndrome. ( 20552815 )
2010
9
A case of lymphedema-distichiasis syndrome carrying a new de novo frameshift FOXC2 mutation. ( 20450314 )
2010
10
Rare association of immunoglobulin A nephropathy and lymphedema-distichiasis syndrome. ( 20124880 )
2010
11
Spinal extradural arachnoid cysts in lymphedema-distichiasis syndrome. ( 20535019 )
2010
12
Lymphedema-distichiasis syndrome without FOXC2 mutation: evidence for chromosome 16 duplication upstream of FOXC2. ( 20218083 )
2009
13
Lymphedema-distichiasis syndrome: a distinct type of primary lymphedema caused by mutations in the FOXC2 gene. ( 18986489 )
2008
14
Novel FOXC2 missense mutation identified in patient with lymphedema-distichiasis syndrome and review. ( 19013876 )
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:

75
# 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 16)
# Gene Variation Type Significance SNP ID Assembly Location
1 FOXC2 FOXC2, 1-BP DEL, 1331A deletion Pathogenic
2 FOXC2 FOXC2, 1-BP INS, 209T insertion Pathogenic
3 FOXC2 FOXC2, 2-BP INS, 201CT insertion Pathogenic
4 FOXC2 NM_005251.2(FOXC2): c.297C> G (p.Tyr99Ter) single nucleotide variant Pathogenic rs104894516 GRCh37 Chromosome 16, 86601238: 86601238
5 FOXC2 NM_005251.2(FOXC2): c.297C> G (p.Tyr99Ter) single nucleotide variant Pathogenic rs104894516 GRCh38 Chromosome 16, 86567632: 86567632
6 FOXC2 FOXC2, 4-BP DUP, NT1093 duplication Pathogenic
7 FOXC2 FOXC2, 11-BP DEL, NT290 deletion Pathogenic
8 FOXC2 FOXC2, 1-BP INS, 589C insertion Pathogenic
9 FOXC2 FOXC2, 1-BP DEL, 505A deletion Pathogenic
10 FOXC2 FOXC2, 8-BP DEL, NT914 deletion Pathogenic
11 FOXC2 FOXC2, 1-BP INS, 1006A insertion Pathogenic
12 FOXC2 FOXC2, 5-BP INS/79-BP DEL, NT602 indel Pathogenic
13 FOXC2 NM_005251.2(FOXC2): c.374C> T (p.Ser125Leu) single nucleotide variant Pathogenic rs121909106 GRCh37 Chromosome 16, 86601315: 86601315
14 FOXC2 NM_005251.2(FOXC2): c.374C> T (p.Ser125Leu) single nucleotide variant Pathogenic rs121909106 GRCh38 Chromosome 16, 86567709: 86567709
15 FOXC2 NM_005251.2(FOXC2): c.362G> A (p.Arg121His) single nucleotide variant Pathogenic rs121909107 GRCh37 Chromosome 16, 86601303: 86601303
16 FOXC2 NM_005251.2(FOXC2): c.362G> A (p.Arg121His) single nucleotide variant Pathogenic rs121909107 GRCh38 Chromosome 16, 86567697: 86567697

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 9.58 FOXC2 FOXL1 FOXP2
2 transcription, DNA-templated GO:0006351 9.54 FOXC2 FOXL1 FOXP2
3 regulation of transcription by RNA polymerase II GO:0006357 9.43 FOXC2 FOXL1 FOXP2
4 cell differentiation GO:0030154 9.33 FOXC2 FOXL1 FOXP2
5 heart development GO:0007507 9.32 FOXC2 FOXL1
6 camera-type eye development GO:0043010 8.96 FOXC2 FOXP2
7 anatomical structure morphogenesis GO:0009653 8.8 FOXC2 FOXL1 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 9.33 FOXC2 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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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