FILS
MCID: FCL084
MIFTS: 34

Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature (FILS)

Categories: Blood diseases, Fetal diseases, Genetic diseases, Immune diseases, Rare diseases, Skin diseases

Aliases & Classifications for Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature

MalaCards integrated aliases for Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature:

Name: Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature 56 73 29 6 39 71
Fils Syndrome 56 58 73 36 13
Livedo Reticularis 43 17 71
Fils 56 73
Facial Dysmorphism-Immunodeficiency-Livedo-Short Stature Syndrome 58
Cutis Marmorata 71

Characteristics:

Orphanet epidemiological data:

58
facial dysmorphism-immunodeficiency-livedo-short stature syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth
one french family has been reported (last curated march 2013)


HPO:

31
facial dysmorphism, immunodeficiency, livedo, and short stature:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:

Orphanet: 58  
Developmental anomalies during embryogenesis
Rare immunological diseases


External Ids:

OMIM 56 615139
KEGG 36 H02370
ICD10 via Orphanet 33 Q87.1
Orphanet 58 ORPHA352712
UMLS 71 C0085642 C0263401 C3554576

Summaries for Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature

UniProtKB/Swiss-Prot : 73 Facial dysmorphism, immunodeficiency, livedo, and short stature: A syndrome characterized by mild facial dysmorphism, mainly malar hypoplasia, livedo on the skin since birth, and immunodeficiency resulting in recurrent infections. Growth impairment is observed during early childhood and results in variable short stature in adulthood.

MalaCards based summary : Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature, also known as fils syndrome, is related to sneddon syndrome and livedoid vasculitis, and has symptoms including pruritus, flushing and icterus. An important gene associated with Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature is POLE (DNA Polymerase Epsilon, Catalytic Subunit), and among its related pathways/superpathways are DNA replication and Base excision repair. Affiliated tissues include skin, bone and t cells, and related phenotypes are bone pain and recurrent respiratory infections

OMIM : 56 FILS syndrome is characterized by mild facial dysmorphism, mainly malar hypoplasia, livedo on the skin since birth, immunodeficiency resulting in recurrent infections, and short stature (summary by Pachlopnik Schmid et al., 2012). (615139)

KEGG : 36 FILS syndrome is a rare autosomal recessive disorder characterized by facial dysmorphism, immunodeficiency, livedo, and short stature. It has been reported that mutations in POLE cause FILS syndrome. POLE encodes the catalytic subunit of DNA polymerase epsilon.

Wikipedia : 74 Livedo reticularis is a common skin finding consisting of a mottled reticulated vascular pattern that... more...

Related Diseases for Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature

Diseases related to Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 206)
# Related Disease Score Top Affiliating Genes
1 sneddon syndrome 12.7
2 livedoid vasculitis 12.1
3 antiphospholipid syndrome 12.0
4 cholesterol embolism 11.8
5 vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome 11.8
6 aortic aneurysm, familial thoracic 6 11.7
7 cutis marmorata telangiectatica congenita 11.5
8 coenzyme q10 deficiency, primary, 2 11.5
9 sting-associated vasculopathy with onset in infancy 11.5
10 familial thoracic aortic aneurysm and aortic dissection 11.5
11 facial infiltrating lipomatosis 11.3
12 vasculitis 10.7
13 lymphoma, hodgkin, classic 10.6
14 exanthem 10.6
15 thrombophilia due to thrombin defect 10.5
16 thrombocytopenia 10.5
17 purpura 10.5
18 lupus erythematosus 10.5
19 primary hyperoxaluria 10.5
20 kidney disease 10.5
21 cerebrovascular disease 10.5
22 vascular disease 10.5
23 raynaud phenomenon 10.5
24 follicular lymphoma 10.5
25 telangiectasis 10.4
26 lymphoma 10.4
27 systemic lupus erythematosus 10.4
28 migraine with or without aura 1 10.4
29 stroke, ischemic 10.4
30 thrombosis 10.4
31 thalassemia 10.4
32 autoimmune disease 10.3
33 covid-19 10.3
34 hypothyroidism 10.3
35 essential thrombocythemia 10.3
36 cryoglobulinemia 10.3
37 calciphylaxis 10.3
38 hemolytic anemia 10.3
39 polyarteritis nodosa 10.3
40 immune deficiency disease 10.3
41 alpha-thalassemia 10.3
42 parkinson disease, late-onset 10.2
43 pheochromocytoma 10.2
44 anemia, autoimmune hemolytic 10.2
45 moyamoya disease 1 10.2
46 hepatitis c virus 10.2
47 adrenal gland pheochromocytoma 10.2
48 infective endocarditis 10.2
49 dermatomyositis 10.2
50 endocarditis 10.2

Graphical network of the top 20 diseases related to Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature:



Diseases related to Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature

Symptoms & Phenotypes for Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature

Human phenotypes related to Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature:

31 (show all 9)
# Description HPO Frequency HPO Source Accession
1 bone pain 31 occasional (7.5%) HP:0002653
2 recurrent respiratory infections 31 HP:0002205
3 abnormal facial shape 31 HP:0001999
4 short stature 31 HP:0004322
5 immunodeficiency 31 HP:0002721
6 malar flattening 31 HP:0000272
7 broad forehead 31 HP:0000337
8 relative macrocephaly 31 HP:0004482
9 telangiectases of the cheeks 31 HP:0007421

Symptoms via clinical synopsis from OMIM:

56
Respiratory:
recurrent respiratory infections

Immunology:
immunodeficiency
decreased igm and igg2
lack of acquired antibodies
low memory b cells
low naive t cells
more
Head And Neck Head:
relative macrocephaly

Skin Nails Hair Skin:
livedo
telangiectasia on the cheeks

Growth Height:
short stature

Head And Neck Face:
broad forehead
malar hypoplasia

Skeletal Limbs:
bone dysplasia (in some patients)
bone pain (in some patients)
lacunar bone lesions (in some patients)
cortical thickening (in some patients)
modeling defects at the long bone diaphyses (in some patients)

Clinical features from OMIM:

615139

UMLS symptoms related to Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature:


pruritus, flushing, icterus, skin manifestations

Drugs & Therapeutics for Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature

Search Clinical Trials , NIH Clinical Center for Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature

Cochrane evidence based reviews: livedo reticularis

Genetic Tests for Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature

Genetic tests related to Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature:

# Genetic test Affiliating Genes
1 Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature 29 POLE

Anatomical Context for Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature

MalaCards organs/tissues related to Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature:

40
Skin, Bone, T Cells, B Cells

Publications for Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature

Articles related to Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature:

# Title Authors PMID Year
1
Polymerase ε1 mutation in a human syndrome with facial dysmorphism, immunodeficiency, livedo, and short stature ("FILS syndrome"). 56 6 61
23230001 2012
2
A patient with polymerase E1 deficiency (POLE1): clinical features and overlap with DNA breakage/instability syndromes. 56
25948378 2015

Variations for Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature

ClinVar genetic disease variations for Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature:

6 (show top 50) (show all 54) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 POLE NM_006231.3(POLE):c.1270C>G (p.Leu424Val)SNV Pathogenic 40046 rs483352909 12:133250250-133250250 12:132673664-132673664
2 POLE NM_006231.3(POLE):c.5867A>T (p.Glu1956Val)SNV Likely pathogenic 547165 rs780843358 12:133210909-133210909 12:132634323-132634323
3 POLE NM_006231.4(POLE):c.2683G>A (p.Ala895Thr)SNV Conflicting interpretations of pathogenicity 265355 rs201115064 12:133240613-133240613 12:132664027-132664027
4 POLE NM_006231.4(POLE):c.5382C>G (p.Ile1794Met)SNV Conflicting interpretations of pathogenicity 240556 rs368364666 12:133215881-133215881 12:132639295-132639295
5 POLE NM_006231.3(POLE):c.4444+3A>GSNV Conflicting interpretations of pathogenicity 41417 rs398122515 12:133219990-133219990 12:132643404-132643404
6 POLE NM_006231.3(POLE):c.4450A>C (p.Ile1484Leu)SNV Conflicting interpretations of pathogenicity 240515 rs772734618 12:133219911-133219911 12:132643325-132643325
7 POLE NM_006231.3(POLE):c.4246G>A (p.Ala1416Thr)SNV Conflicting interpretations of pathogenicity 240508 rs146711942 12:133220467-133220467 12:132643881-132643881
8 POLE NM_006231.3(POLE):c.5912A>G (p.Asn1971Ser)SNV Conflicting interpretations of pathogenicity 439278 rs772127913 12:133210864-133210864 12:132634278-132634278
9 POLE NM_006231.3(POLE):c.4759G>A (p.Val1587Ile)SNV Uncertain significance 473692 rs372388555 12:133219285-133219285 12:132642699-132642699
10 POLE NM_006231.4(POLE):c.4522C>G (p.Arg1508Gly)SNV Uncertain significance 473670 rs766511597 12:133219839-133219839 12:132643253-132643253
11 POLE NM_006231.3(POLE):c.73G>T (p.Ala25Ser)SNV Uncertain significance 473825 rs773204331 12:133257855-133257855 12:132681269-132681269
12 POLE NM_006231.3(POLE):c.68A>G (p.Asp23Gly)SNV Uncertain significance 473820 rs765898876 12:133257860-133257860 12:132681274-132681274
13 POLE NM_006231.3(POLE):c.2362G>A (p.Ala788Thr)SNV Uncertain significance 473524 rs896350761 12:133241994-133241994 12:132665408-132665408
14 POLE NM_006231.3(POLE):c.3652G>A (p.Val1218Ile)SNV Uncertain significance 484447 rs756246229 12:133226406-133226406 12:132649820-132649820
15 POLE NM_006231.3(POLE):c.1041G>T (p.Trp347Cys)SNV Uncertain significance 484505 rs1048183984 12:133252386-133252386 12:132675800-132675800
16 POLE NM_006231.4(POLE):c.4477G>A (p.Ala1493Thr)SNV Uncertain significance 403334 rs748522633 12:133219884-133219884 12:132643298-132643298
17 POLE NM_006231.4(POLE):c.6445C>T (p.Arg2149Cys)SNV Uncertain significance 405704 rs771490182 12:133202789-133202789 12:132626203-132626203
18 POLE NM_006231.3(POLE):c.4285A>T (p.Thr1429Ser)SNV Uncertain significance 405827 rs759497382 12:133220428-133220428 12:132643842-132643842
19 POLE NM_006231.3(POLE):c.3857G>A (p.Arg1286His)SNV Uncertain significance 405702 rs771823596 12:133226040-133226040 12:132649454-132649454
20 POLE NM_006231.3(POLE):c.5866G>A (p.Glu1956Lys)SNV Uncertain significance 405680 rs749992643 12:133210910-133210910 12:132634324-132634324
21 POLE NM_006231.4(POLE):c.5761A>G (p.Asn1921Asp)SNV Uncertain significance 405854 rs771980261 12:133212528-133212528 12:132635942-132635942
22 POLE NM_006231.3(POLE):c.4145G>A (p.Arg1382His)SNV Uncertain significance 405766 rs143229302 12:133225519-133225519 12:132648933-132648933
23 POLE NM_006231.3(POLE):c.266A>C (p.Asp89Ala)SNV Uncertain significance 405904 rs756843283 12:133257212-133257212 12:132680626-132680626
24 POLE NM_006231.3(POLE):c.5035C>T (p.Arg1679Cys)SNV Uncertain significance 405795 rs768244569 12:133218901-133218901 12:132642315-132642315
25 POLE NM_006231.3(POLE):c.4270G>A (p.Glu1424Lys)SNV Uncertain significance 405695 rs575419120 12:133220443-133220443 12:132643857-132643857
26 POLE NM_006231.4(POLE):c.2090C>T (p.Pro697Leu)SNV Uncertain significance 405654 rs36120395 12:133245025-133245025 12:132668439-132668439
27 POLE NM_006231.3(POLE):c.2131T>C (p.Ser711Pro)SNV Uncertain significance 405853 rs374800058 12:133244984-133244984 12:132668398-132668398
28 POLE NM_006231.3(POLE):c.575C>T (p.Ser192Phe)SNV Uncertain significance 405901 rs1060500891 12:133256086-133256086 12:132679500-132679500
29 POLE NM_006231.3(POLE):c.431A>G (p.His144Arg)SNV Uncertain significance 405687 rs755709875 12:133256230-133256230 12:132679644-132679644
30 POLE NM_006231.3(POLE):c.1108C>A (p.Pro370Thr)SNV Uncertain significance 423238 rs576578672 12:133252102-133252102 12:132675516-132675516
31 POLE NM_006231.3(POLE):c.2773T>C (p.Ser925Pro)SNV Uncertain significance 240444 rs141552148 12:133238204-133238204 12:132661618-132661618
32 POLE NM_006231.3(POLE):c.2359G>A (p.Asp787Asn)SNV Uncertain significance 240433 rs878854851 12:133241997-133241997 12:132665411-132665411
33 POLE NM_006231.3(POLE):c.2276G>A (p.Arg759His)SNV Uncertain significance 240431 rs746774432 12:133244132-133244132 12:132667546-132667546
34 POLE NM_006231.3(POLE):c.1064A>G (p.Lys355Arg)SNV Uncertain significance 240374 rs141396559 12:133252363-133252363 12:132675777-132675777
35 POLE NM_006231.3(POLE):c.274A>C (p.Ser92Arg)SNV Uncertain significance 240443 rs758382516 12:133257204-133257204 12:132680618-132680618
36 POLE NM_006231.4(POLE):c.154C>T (p.Arg52Trp)SNV Uncertain significance 240396 rs115452881 12:133257774-133257774 12:132681188-132681188
37 POLE NM_006231.3(POLE):c.4172C>G (p.Ser1391Cys)SNV Uncertain significance 246358 rs149145495 12:133220541-133220541 12:132643955-132643955
38 POLE NM_006231.3(POLE):c.3230G>A (p.Arg1077His)SNV Uncertain significance 246318 rs768950975 12:133235926-133235926 12:132659340-132659340
39 POLE NM_006231.3(POLE):c.1868A>G (p.Tyr623Cys)SNV Uncertain significance 221157 rs150564856 12:133245452-133245452 12:132668866-132668866
40 POLE NM_006231.4(POLE):c.6730C>T (p.Leu2244Phe)SNV Uncertain significance 240616 rs375741031 12:133201508-133201508 12:132624922-132624922
41 POLE NM_006231.4(POLE):c.6674G>A (p.Arg2225His)SNV Uncertain significance 240612 rs538875477 12:133201564-133201564 12:132624978-132624978
42 POLE NM_006231.3(POLE):c.6476G>A (p.Arg2159His)SNV Uncertain significance 240596 rs373092830 12:133202758-133202758 12:132626172-132626172
43 POLE NM_006231.3(POLE):c.6050G>A (p.Arg2017His)SNV Uncertain significance 240582 rs144178150 12:133209336-133209336 12:132632750-132632750
44 POLE NM_006231.3(POLE):c.6136G>A (p.Gly2046Arg)SNV Uncertain significance 540694 rs1462887616 12:133209250-133209250 12:132632664-132632664
45 POLE NM_006231.3(POLE):c.2113C>T (p.Arg705Trp)SNV Uncertain significance 540760 rs200621883 12:133245002-133245002 12:132668416-132668416
46 POLE NM_006231.3(POLE):c.1784A>G (p.Asn595Ser)SNV Uncertain significance 540799 rs969500436 12:133248811-133248811 12:132672225-132672225
47 POLE NM_006231.3(POLE):c.198G>A (p.Met66Ile)SNV Uncertain significance 540773 rs764962999 12:133257730-133257730 12:132681144-132681144
48 POLE NM_006231.3(POLE):c.2384A>G (p.Lys795Arg)SNV Uncertain significance 540644 rs867677414 12:133241972-133241972 12:132665386-132665386
49 POLE NM_006231.3(POLE):c.4901G>A (p.Arg1634His)SNV Uncertain significance 240545 rs760149463 12:133219143-133219143 12:132642557-132642557
50 POLE NM_006231.3(POLE):c.4603G>A (p.Gly1535Ser)SNV Uncertain significance 240530 rs138564205 12:133219531-133219531 12:132642945-132642945

Expression for Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature

Search GEO for disease gene expression data for Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature.

Pathways for Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature

Pathways related to Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature according to KEGG:

36
# Name Kegg Source Accession
1 DNA replication hsa03030
2 Base excision repair hsa03410
3 Nucleotide excision repair hsa03420

GO Terms for Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature

Sources for Facial Dysmorphism, Immunodeficiency, Livedo, and Short Stature

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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