U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Facial dysmorphism-immunodeficiency-livedo-short stature syndrome(FILS)

MedGen UID:
767490
Concept ID:
C3554576
Disease or Syndrome
Synonym: Facial dysmorphism, immunodeficiency, livedo, and short stature
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): POLE (12q24.33)
 
Monarch Initiative: MONDO:0014058
OMIM®: 615139
Orphanet: ORPHA352712

Definition

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). [from OMIM]

Clinical features

From HPO
Bone pain
MedGen UID:
57489
Concept ID:
C0151825
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to bone.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Relative macrocephaly
MedGen UID:
338607
Concept ID:
C1849075
Congenital Abnormality
A relatively mild degree of macrocephaly in which the head circumference is not above two standard deviations from the mean, but appears dysproportionately large when other factors such as body stature are taken into account.
Metaphyseal striations
MedGen UID:
376512
Concept ID:
C1849081
Finding
Longitudinal densities on radiographs located in a metaphysis (the narrow region of a long bone between the epiphysis and the diaphysis).
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Bronchiectasis
MedGen UID:
14234
Concept ID:
C0006267
Disease or Syndrome
Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.
Recurrent upper respiratory tract infections
MedGen UID:
154380
Concept ID:
C0581381
Disease or Syndrome
An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).
Recurrent lower respiratory tract infections
MedGen UID:
756211
Concept ID:
C3163798
Disease or Syndrome
An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections.
Immunodeficiency
MedGen UID:
7034
Concept ID:
C0021051
Disease or Syndrome
Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.
Decreased circulating total IgM
MedGen UID:
116095
Concept ID:
C0239989
Finding
An abnormally decreased level of immunoglobulin M (IgM) in blood.
Broad forehead
MedGen UID:
338610
Concept ID:
C1849089
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead.
Livedo
MedGen UID:
568434
Concept ID:
C0332579
Finding
A reddish-blue mottled condition of skin caused by inflammation of the cutaneous blood vessels.
Telangiectases of the cheeks
MedGen UID:
767501
Concept ID:
C3554587
Finding
Telangiectases (small dilated blood vessels) located near the surface of the skin of the cheeks.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFacial dysmorphism-immunodeficiency-livedo-short stature syndrome
Follow this link to review classifications for Facial dysmorphism-immunodeficiency-livedo-short stature syndrome in Orphanet.

Professional guidelines

PubMed

Gavril EC, Nucă I, Pânzaru MC, Ivanov AV, Mihai CT, Antoci LM, Ciobanu CG, Rusu C, Popescu R
Genes (Basel) 2023 Feb 11;14(2) doi: 10.3390/genes14020465. PMID: 36833393Free PMC Article
Romano AA, Allanson JE, Dahlgren J, Gelb BD, Hall B, Pierpont ME, Roberts AE, Robinson W, Takemoto CM, Noonan JA
Pediatrics 2010 Oct;126(4):746-59. Epub 2010 Sep 27 doi: 10.1542/peds.2009-3207. PMID: 20876176
Tartaglia M, Kalidas K, Shaw A, Song X, Musat DL, van der Burgt I, Brunner HG, Bertola DR, Crosby A, Ion A, Kucherlapati RS, Jeffery S, Patton MA, Gelb BD
Am J Hum Genet 2002 Jun;70(6):1555-63. Epub 2002 May 1 doi: 10.1086/340847. PMID: 11992261Free PMC Article

Recent clinical studies

Etiology

Chen M, Miao H, Liang H, Ke X, Yang H, Gong F, Wang L, Duan L, Chen S, Pan H, Zhu H
Front Endocrinol (Lausanne) 2022;13:820001. Epub 2022 Feb 16 doi: 10.3389/fendo.2022.820001. PMID: 35250876Free PMC Article
Roberts AE, Allanson JE, Tartaglia M, Gelb BD
Lancet 2013 Jan 26;381(9863):333-42. Epub 2013 Jan 10 doi: 10.1016/S0140-6736(12)61023-X. PMID: 23312968Free PMC Article
Cassidy SB, Schwartz S, Miller JL, Driscoll DJ
Genet Med 2012 Jan;14(1):10-26. Epub 2011 Sep 26 doi: 10.1038/gim.0b013e31822bead0. PMID: 22237428
Romano AA, Allanson JE, Dahlgren J, Gelb BD, Hall B, Pierpont ME, Roberts AE, Robinson W, Takemoto CM, Noonan JA
Pediatrics 2010 Oct;126(4):746-59. Epub 2010 Sep 27 doi: 10.1542/peds.2009-3207. PMID: 20876176
Tartaglia M, Kalidas K, Shaw A, Song X, Musat DL, van der Burgt I, Brunner HG, Bertola DR, Crosby A, Ion A, Kucherlapati RS, Jeffery S, Patton MA, Gelb BD
Am J Hum Genet 2002 Jun;70(6):1555-63. Epub 2002 May 1 doi: 10.1086/340847. PMID: 11992261Free PMC Article

Diagnosis

Chen M, Miao H, Liang H, Ke X, Yang H, Gong F, Wang L, Duan L, Chen S, Pan H, Zhu H
Front Endocrinol (Lausanne) 2022;13:820001. Epub 2022 Feb 16 doi: 10.3389/fendo.2022.820001. PMID: 35250876Free PMC Article
Zenker M, Edouard T, Blair JC, Cappa M
Arch Dis Child 2022 Dec;107(12):1073-1078. Epub 2022 Mar 4 doi: 10.1136/archdischild-2021-322858. PMID: 35246453Free PMC Article
Vargas Lebrón C, Ruiz Montesino MD, Moreira Navarrete V, Aróstegui Gorospe JI
Reumatol Clin (Engl Ed) 2020 Nov-Dec;16(6):499-501. Epub 2018 Dec 3 doi: 10.1016/j.reuma.2018.08.015. PMID: 30522940
Turner AM
J Paediatr Child Health 2014 Oct;50(10):E14-20. Epub 2011 Jul 19 doi: 10.1111/j.1440-1754.2010.01970.x. PMID: 21771153
Bögershausen N, Wollnik B
Clin Genet 2013 Mar;83(3):201-11. Epub 2012 Nov 26 doi: 10.1111/cge.12051. PMID: 23131014

Therapy

Chen M, Miao H, Liang H, Ke X, Yang H, Gong F, Wang L, Duan L, Chen S, Pan H, Zhu H
Front Endocrinol (Lausanne) 2022;13:820001. Epub 2022 Feb 16 doi: 10.3389/fendo.2022.820001. PMID: 35250876Free PMC Article
Baglam T, Binnetoglu A, Fatih Topuz M, Baş Ikizoglu N, Ersu R, Turan S, Sarı M
Int J Pediatr Otorhinolaryngol 2017 Apr;95:91-96. Epub 2017 Feb 11 doi: 10.1016/j.ijporl.2017.02.009. PMID: 28576543
McCartney CR, Marshall JC
N Engl J Med 2016 Jul 7;375(1):54-64. doi: 10.1056/NEJMcp1514916. PMID: 27406348Free PMC Article
Tylki-Szymańska A
Pediatr Endocrinol Rev 2014 Sep;12 Suppl 1:107-13. PMID: 25345092
Laxova R
Adv Pediatr 1994;41:305-42. PMID: 7992687

Prognosis

Pérez-Riera AR, Barbosa-Barros R, Samesina N, Pastore CA, Scanavacca M, Daminello-Raimundo R, de Abreu LC, Nikus K, Brugada P
Cardiol Rev 2021 Jul-Aug 01;29(4):165-177. doi: 10.1097/CRD.0000000000000326. PMID: 32947483
Le Goff C, Michot C, Cormier-Daire V
Clin Genet 2014 Jun;85(6):503-13. Epub 2014 Apr 2 doi: 10.1111/cge.12365. PMID: 24580733
Turner AM
J Paediatr Child Health 2014 Oct;50(10):E14-20. Epub 2011 Jul 19 doi: 10.1111/j.1440-1754.2010.01970.x. PMID: 21771153
Roberts AE, Allanson JE, Tartaglia M, Gelb BD
Lancet 2013 Jan 26;381(9863):333-42. Epub 2013 Jan 10 doi: 10.1016/S0140-6736(12)61023-X. PMID: 23312968Free PMC Article
Sarkozy A, Digilio MC, Dallapiccola B
Orphanet J Rare Dis 2008 May 27;3:13. doi: 10.1186/1750-1172-3-13. PMID: 18505544Free PMC Article

Clinical prediction guides

Gavril EC, Nucă I, Pânzaru MC, Ivanov AV, Mihai CT, Antoci LM, Ciobanu CG, Rusu C, Popescu R
Genes (Basel) 2023 Feb 11;14(2) doi: 10.3390/genes14020465. PMID: 36833393Free PMC Article
Martinez-Cayuelas E, Blanco-Kelly F, Lopez-Grondona F, Swafiri ST, Lopez-Rodriguez R, Losada-Del Pozo R, Mahillo-Fernandez I, Moreno B, Rodrigo-Moreno M, Casas-Alba D, Lopez-Gonzalez A, García-Miñaúr S, Ángeles Mori M, Pacio-Minguez M, Rikeros-Orozco E, Santos-Simarro F, Cruz-Rojo J, Quesada-Espinosa JF, Sanchez-Calvin MT, Sanchez-Del Pozo J, Bernado Fonz R, Isidoro-Garcia M, Ruiz-Ayucar I, Alvarez-Mora MI, Blanco-Lago R, De Azua B, Eiris J, Garcia-Peñas JJ, Gil-Fournier B, Gomez-Lado C, Irazabal N, Lopez-Gonzalez V, Madrigal I, Malaga I, Martinez-Menendez B, Ramiro-Leon S, Garcia-Hoyos M, Prieto-Matos P, Lopez-Pison J, Aguilera-Albesa S, Alvarez S, Fernández-Jaén A, Llano-Rivas I, Gener-Querol B, Ayuso C, Arteche-Lopez A, Palomares-Bralo M, Cueto-González A, Valenzuela I, Martinez-Monseny A, Lorda-Sanchez I, Almoguera B
J Med Genet 2023 Jul;60(7):644-654. Epub 2022 Nov 29 doi: 10.1136/jmg-2022-108632. PMID: 36446582
Pérez-Riera AR, Barbosa-Barros R, Samesina N, Pastore CA, Scanavacca M, Daminello-Raimundo R, de Abreu LC, Nikus K, Brugada P
Cardiol Rev 2021 Jul-Aug 01;29(4):165-177. doi: 10.1097/CRD.0000000000000326. PMID: 32947483
Athota JP, Bhat M, Nampoothiri S, Gowrishankar K, Narayanachar SG, Puttamallesh V, Farooque MO, Shetty S
BMC Med Genet 2020 Mar 12;21(1):50. doi: 10.1186/s12881-020-0986-5. PMID: 32164556Free PMC Article
Moortgat S, Berland S, Aukrust I, Maystadt I, Baker L, Benoit V, Caro-Llopis A, Cooper NS, Debray FG, Faivre L, Gardeitchik T, Haukanes BI, Houge G, Kivuva E, Martinez F, Mehta SG, Nassogne MC, Powell-Hamilton N, Pfundt R, Rosello M, Prescott T, Vasudevan P, van Loon B, Verellen-Dumoulin C, Verloes A, Lippe CV, Wakeling E, Wilkie AOM, Wilson L, Yuen A, Study D, Low KJ, Newbury-Ecob RA
Eur J Hum Genet 2018 Jan;26(1):64-74. Epub 2017 Nov 27 doi: 10.1038/s41431-017-0038-6. PMID: 29180823Free PMC Article

Recent systematic reviews

Perge K, Capel E, Senée V, Julier C, Vigouroux C, Nicolino M
Rev Endocr Metab Disord 2024 Oct;25(5):827-838. Epub 2024 Jul 17 doi: 10.1007/s11154-024-09894-w. PMID: 39017987Free PMC Article
Patti G, Scaglione M, Maiorano NG, Rosti G, Divizia MT, Camia T, De Rose EL, Zucconi A, Casalini E, Napoli F, Di Iorgi N, Maghnie M
Front Endocrinol (Lausanne) 2023;14:1213098. Epub 2023 Jul 28 doi: 10.3389/fendo.2023.1213098. PMID: 37576960Free PMC Article
de Sousa Lima Strafacci A, Fernandes Camargo J, Bertapelli F, Guerra Júnior G
J Appl Genet 2020 May;61(2):205-212. Epub 2020 Mar 10 doi: 10.1007/s13353-020-00551-x. PMID: 32157657

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...