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Pancytopenia-developmental delay syndrome(BMFS2)

MedGen UID:
816680
Concept ID:
C3810350
Disease or Syndrome
Synonym: Bone marrow failure syndrome 2
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): ERCC6L2 (9q22.32)
 
Monarch Initiative: MONDO:0014317
OMIM®: 615715
Orphanet: ORPHA401764

Definition

Bone marrow failure syndrome-2 is an autosomal recessive disorder characterized by trilineage bone marrow failure, learning disabilities, and microcephaly. Cutaneous features and increased chromosome breakage are not features (Tummala et al., 2014). For a discussion of genetic heterogeneity of BMFS, see BMFS1 (614675). [from OMIM]

Clinical features

From HPO
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Bone marrow hypocellularity
MedGen UID:
383749
Concept ID:
C1855710
Finding
A reduced number of hematopoietic cells present in the bone marrow relative to marrow fat.
Neonatal hypotonia
MedGen UID:
412209
Concept ID:
C2267233
Disease or Syndrome
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Leukopenia
MedGen UID:
6073
Concept ID:
C0023530
Disease or Syndrome
An abnormal decreased number of leukocytes in the blood.
Cutaneous photosensitivity
MedGen UID:
87601
Concept ID:
C0349506
Pathologic Function
An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPancytopenia-developmental delay syndrome
Follow this link to review classifications for Pancytopenia-developmental delay syndrome in Orphanet.

Professional guidelines

PubMed

Nierenberg AA, Agustini B, Köhler-Forsberg O, Cusin C, Katz D, Sylvia LG, Peters A, Berk M
JAMA 2023 Oct 10;330(14):1370-1380. doi: 10.1001/jama.2023.18588. PMID: 37815563
Teede HJ, Tay CT, Laven JJE, Dokras A, Moran LJ, Piltonen TT, Costello MF, Boivin J, Redman LM, Boyle JA, Norman RJ, Mousa A, Joham AE
J Clin Endocrinol Metab 2023 Sep 18;108(10):2447-2469. doi: 10.1210/clinem/dgad463. PMID: 37580314Free PMC Article
Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC Jr, Sperling L, Virani SS, Yeboah J
Circulation 2019 Jun 18;139(25):e1082-e1143. Epub 2018 Nov 10 doi: 10.1161/CIR.0000000000000625. PMID: 30586774Free PMC Article

Recent clinical studies

Etiology

Sorber R, Hicks CW
Curr Cardiol Rep 2022 Mar;24(3):209-216. Epub 2022 Jan 14 doi: 10.1007/s11886-022-01642-3. PMID: 35029783Free PMC Article
Vilacosta I, San Román JA, di Bartolomeo R, Eagle K, Estrera AL, Ferrera C, Kaji S, Nienaber CA, Riambau V, Schäfers HJ, Serrano FJ, Song JK, Maroto L
J Am Coll Cardiol 2021 Nov 23;78(21):2106-2125. doi: 10.1016/j.jacc.2021.09.022. PMID: 34794692
Morello F, Santoro M, Fargion AT, Grifoni S, Nazerian P
Intern Emerg Med 2021 Jan;16(1):171-181. Epub 2020 May 1 doi: 10.1007/s11739-020-02354-8. PMID: 32358680
Rosenfeld E, Ganguly A, De Leon DD
Am J Med Genet C Semin Med Genet 2019 Dec;181(4):682-692. Epub 2019 Aug 14 doi: 10.1002/ajmg.c.31737. PMID: 31414570Free PMC Article
Camilleri M, Chedid V, Ford AC, Haruma K, Horowitz M, Jones KL, Low PA, Park SY, Parkman HP, Stanghellini V
Nat Rev Dis Primers 2018 Nov 1;4(1):41. doi: 10.1038/s41572-018-0038-z. PMID: 30385743

Diagnosis

Sorber R, Hicks CW
Curr Cardiol Rep 2022 Mar;24(3):209-216. Epub 2022 Jan 14 doi: 10.1007/s11886-022-01642-3. PMID: 35029783Free PMC Article
Morello F, Santoro M, Fargion AT, Grifoni S, Nazerian P
Intern Emerg Med 2021 Jan;16(1):171-181. Epub 2020 May 1 doi: 10.1007/s11739-020-02354-8. PMID: 32358680
Rosenfeld E, Ganguly A, De Leon DD
Am J Med Genet C Semin Med Genet 2019 Dec;181(4):682-692. Epub 2019 Aug 14 doi: 10.1002/ajmg.c.31737. PMID: 31414570Free PMC Article
Tartaglia N, Ayari N, Howell S, D'Epagnier C, Zeitler P
Acta Paediatr 2011 Jun;100(6):851-60. Epub 2011 Apr 8 doi: 10.1111/j.1651-2227.2011.02235.x. PMID: 21342258Free PMC Article
Otter M, Schrander-Stumpel CT, Curfs LM
Eur J Hum Genet 2010 Mar;18(3):265-71. Epub 2009 Jul 1 doi: 10.1038/ejhg.2009.109. PMID: 19568271Free PMC Article

Therapy

Goetzl L
Am J Obstet Gynecol 2023 May;228(5S):S1274-S1282. Epub 2023 Mar 20 doi: 10.1016/j.ajog.2022.11.002. PMID: 36997396
Calvani M, Anania C, Bianchi A, D'Auria E, Cardinale F, Votto M, Martelli A, Tosca M, Chiappini E, Brambilla I, Miraglia Del Giudice M, Caffarelli C
Acta Biomed 2021 Nov 29;92(S7):e2021518. doi: 10.23750/abm.v92iS7.12394. PMID: 34842596Free PMC Article
Auld F, Maschauer EL, Morrison I, Skene DJ, Riha RL
Sleep Med Rev 2017 Aug;34:10-22. Epub 2016 Jul 20 doi: 10.1016/j.smrv.2016.06.005. PMID: 28648359
Reintam Blaser A, Starkopf J, Alhazzani W, Berger MM, Casaer MP, Deane AM, Fruhwald S, Hiesmayr M, Ichai C, Jakob SM, Loudet CI, Malbrain ML, Montejo González JC, Paugam-Burtz C, Poeze M, Preiser JC, Singer P, van Zanten AR, De Waele J, Wendon J, Wernerman J, Whitehouse T, Wilmer A, Oudemans-van Straaten HM; ESICM Working Group on Gastrointestinal Function
Intensive Care Med 2017 Mar;43(3):380-398. Epub 2017 Feb 6 doi: 10.1007/s00134-016-4665-0. PMID: 28168570Free PMC Article
Herxheimer A, Petrie KJ
Cochrane Database Syst Rev 2002;(2):CD001520. doi: 10.1002/14651858.CD001520. PMID: 12076414

Prognosis

Saper VE, Chen G, Deutsch GH, Guillerman RP, Birgmeier J, Jagadeesh K, Canna S, Schulert G, Deterding R, Xu J, Leung AN, Bouzoubaa L, Abulaban K, Baszis K, Behrens EM, Birmingham J, Casey A, Cidon M, Cron RQ, De A, De Benedetti F, Ferguson I, Fishman MP, Goodman SI, Graham TB, Grom AA, Haines K, Hazen M, Henderson LA, Ho A, Ibarra M, Inman CJ, Jerath R, Khawaja K, Kingsbury DJ, Klein-Gitelman M, Lai K, Lapidus S, Lin C, Lin J, Liptzin DR, Milojevic D, Mombourquette J, Onel K, Ozen S, Perez M, Phillippi K, Prahalad S, Radhakrishna S, Reinhardt A, Riskalla M, Rosenwasser N, Roth J, Schneider R, Schonenberg-Meinema D, Shenoi S, Smith JA, Sönmez HE, Stoll ML, Towe C, Vargas SO, Vehe RK, Young LR, Yang J, Desai T, Balise R, Lu Y, Tian L, Bejerano G, Davis MM, Khatri P, Mellins ED; Childhood Arthritis and Rheumatology Research Alliance Registry Investigators
Ann Rheum Dis 2019 Dec;78(12):1722-1731. Epub 2019 Sep 27 doi: 10.1136/annrheumdis-2019-216040. PMID: 31562126Free PMC Article
Rosenfeld E, Ganguly A, De Leon DD
Am J Med Genet C Semin Med Genet 2019 Dec;181(4):682-692. Epub 2019 Aug 14 doi: 10.1002/ajmg.c.31737. PMID: 31414570Free PMC Article
McKiernan P
Clin Res Hepatol Gastroenterol 2012 Jun;36(3):253-6. Epub 2012 May 18 doi: 10.1016/j.clinre.2012.03.018. PMID: 22609294
Miller DH, Chard DT, Ciccarelli O
Lancet Neurol 2012 Feb;11(2):157-69. doi: 10.1016/S1474-4422(11)70274-5. PMID: 22265211
Souka AP, Von Kaisenberg CS, Hyett JA, Sonek JD, Nicolaides KH
Am J Obstet Gynecol 2005 Apr;192(4):1005-21. doi: 10.1016/j.ajog.2004.12.093. PMID: 15846173

Clinical prediction guides

Story CM, Gerber GF, Chaturvedi S
Hematology Am Soc Hematol Educ Program 2023 Dec 8;2023(1):745-753. doi: 10.1182/hematology.2023000501. PMID: 38066937Free PMC Article
Sanchez-Jimeno C, Blanco-Kelly F, López-Grondona F, Losada-Del Pozo R, Moreno B, Rodrigo-Moreno M, Martinez-Cayuelas E, Riveiro-Alvarez R, Fenollar-Cortés M, Ayuso C, Rodríguez de Alba M, Lorda-Sanchez I, Almoguera B
Genes (Basel) 2021 Aug 30;12(9) doi: 10.3390/genes12091360. PMID: 34573342Free PMC Article
Yates TM, Drucker M, Barnicoat A, Low K, Gerkes EH, Fry AE, Parker MJ, O'Driscoll M, Charles P, Cox H, Marey I, Keren B, Rinne T, McEntagart M, Ramachandran V, Drury S, Vansenne F, Sival DA, Herkert JC, Callewaert B, Tan WH, Balasubramanian M
Hum Mutat 2020 May;41(5):1042-1050. Epub 2020 Mar 5 doi: 10.1002/humu.24001. PMID: 32097528
Rosenfeld E, Ganguly A, De Leon DD
Am J Med Genet C Semin Med Genet 2019 Dec;181(4):682-692. Epub 2019 Aug 14 doi: 10.1002/ajmg.c.31737. PMID: 31414570Free 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

González-Rubino JB, Vinolo-Gil MJ, Martín-Valero R
Support Care Cancer 2023 Apr 12;31(5):257. doi: 10.1007/s00520-023-07666-x. PMID: 37043039Free PMC Article
Tutal E, Ozaras R, Leblebicioglu H
Travel Med Infect Dis 2022 May-Jun;47:102314. Epub 2022 Mar 18 doi: 10.1016/j.tmaid.2022.102314. PMID: 35307540Free PMC Article
Gil Martínez V, Avedillo Salas A, Santander Ballestín S
Nutrients 2022 Feb 28;14(5) doi: 10.3390/nu14051033. PMID: 35268010Free PMC Article
Payne LE, Gagnon DJ, Riker RR, Seder DB, Glisic EK, Morris JG, Fraser GL
Crit Care 2017 Nov 14;21(1):276. doi: 10.1186/s13054-017-1856-1. PMID: 29137682Free PMC Article
van Sleuwen BE, Engelberts AC, Boere-Boonekamp MM, Kuis W, Schulpen TW, L'Hoir MP
Pediatrics 2007 Oct;120(4):e1097-106. doi: 10.1542/peds.2006-2083. PMID: 17908730

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