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Bone marrow failure syndrome 5(BMFS5)

MedGen UID:
1648380
Concept ID:
C4748488
Disease or Syndrome
Synonyms: BMFS5; BONE MARROW FAILURE SYNDROME 5
 
Gene (location): TP53 (17p13.1)
 
Monarch Initiative: MONDO:0032573
OMIM®: 618165

Definition

Bone marrow failure syndrome-5 (BMFS5) is a hematologic disorder characterized by infantile onset of severe red cell anemia requiring transfusion. Additional features include hypogammaglobulinemia, poor growth with microcephaly, developmental delay, and seizures (summary by Toki et al., 2018) For a discussion of genetic heterogeneity of BMFS, see BMFS1 (614675). [from OMIM]

Clinical features

From HPO
Testicular atrophy
MedGen UID:
57626
Concept ID:
C0156312
Disease or Syndrome
Wasting (atrophy) of the testicle (the male gonad) manifested by a decrease in size and potentially by a loss of fertility.
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).
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Pure red-cell aplasia
MedGen UID:
11154
Concept ID:
C0034902
Disease or Syndrome
A type of anemia resulting from suppression of erythropoiesis with little or no abnormality of leukocyte or platelet production. Erythroblasts are virtually absent in bone marrow; however, leukocyte and platelet production show little or no reduction.
Erythroid hypoplasia
MedGen UID:
488912
Concept ID:
C0542035
Disease or Syndrome
Decreased count of erythroid precursor cells, that is, erythroid lineage cells in the bone marrow.
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Pulmonary fibrosis
MedGen UID:
11028
Concept ID:
C0034069
Disease or Syndrome
Replacement of normal lung tissues by fibroblasts and collagen.
Decreased circulating antibody concentration
MedGen UID:
892481
Concept ID:
C4048270
Finding
An abnormally decreased level of immunoglobulin in blood.
Oral mucosa leukoplakia
MedGen UID:
9738
Concept ID:
C0023532
Neoplastic Process
A thickened white patch on the oral mucosa that cannot be rubbed off.
Nail dystrophy
MedGen UID:
66368
Concept ID:
C0221260
Disease or Syndrome
Onychodystrophy (nail dystrophy) refers to nail changes apart from changes of the color (nail dyschromia) and involves partial or complete disruption of the various keratinous layers of the nail plate.
Reticular hyperpigmentation
MedGen UID:
338832
Concept ID:
C1851972
Finding
Increased pigmentation of the skin with a netlike (reticular) pattern.
Hypogonadism
MedGen UID:
5711
Concept ID:
C0020619
Disease or Syndrome
A decreased functionality of the gonad.
Short telomere length
MedGen UID:
1627435
Concept ID:
C4531138
Anatomical Abnormality
An abnormal reduction in telomere length. Telomeres are non-coding, repetitive sequences of DNA at the ends of the chromosomes of eukaryotic cells which become shorter as cells divide, and when telomere attrition reaches its limit, cell proliferation arrest, senescence, and apoptosis can occur.

Professional guidelines

PubMed

Wlodarski MW, Vlachos A, Farrar JE, Da Costa LM, Kattamis A, Dianzani I, Belendez C, Unal S, Tamary H, Pasauliene R, Pospisilova D, de la Fuente J, Iskander D, Wolfe L, Liu JM, Shimamura A, Albrecht K, Lausen B, Bechensteen AG, Tedgard U, Puzik A, Quarello P, Ramenghi U, Bartels M, Hengartner H, Farah RA, Al Saleh M, Hamidieh AA, Yang W, Ito E, Kook H, Ovsyannikova G, Kager L, Gleizes PE, Dalle JH, Strahm B, Niemeyer CM, Lipton JM, Leblanc TM; international Diamond-Blackfan anaemia syndrome guideline panel
Lancet Haematol 2024 May;11(5):e368-e382. doi: 10.1016/S2352-3026(24)00063-2. PMID: 38697731
Mellinghoff SC, Panse J, Alakel N, Behre G, Buchheidt D, Christopeit M, Hasenkamp J, Kiehl M, Koldehoff M, Krause SW, Lehners N, von Lilienfeld-Toal M, Löhnert AY, Maschmeyer G, Teschner D, Ullmann AJ, Penack O, Ruhnke M, Mayer K, Ostermann H, Wolf HH, Cornely OA
Ann Hematol 2018 Feb;97(2):197-207. Epub 2017 Dec 7 doi: 10.1007/s00277-017-3196-2. PMID: 29218389Free PMC Article
Stauder R, Valent P, Theurl I
Blood 2018 Feb 1;131(5):505-514. Epub 2017 Nov 15 doi: 10.1182/blood-2017-07-746446. PMID: 29141943

Recent clinical studies

Etiology

Ji J, Wan Z, Ruan J, Yang Y, Hu Q, Chen Z, Yang C, Chen M, Han B
Blood Cancer J 2023 Sep 19;13(1):146. doi: 10.1038/s41408-023-00921-8. PMID: 37726286Free PMC Article
Gurnari C, Pagliuca S, Prata PH, Galimard JE, Catto LFB, Larcher L, Sebert M, Allain V, Patel BJ, Durmaz A, Pinto AL, Inacio MCB, Hernandez L, Dhedin N, Caillat-Zucman S, Clappier E, Sicre de Fontbrune F, Voso MT, Visconte V, Peffault de Latour R, Soulier J, Calado RT, Socié G, Maciejewski JP
J Clin Oncol 2023 Jan 1;41(1):132-142. Epub 2022 Sep 2 doi: 10.1200/JCO.22.00710. PMID: 36054881Free PMC Article
Aluri J, Bach A, Kaviany S, Chiquetto Paracatu L, Kitcharoensakkul M, Walkiewicz MA, Putnam CD, Shinawi M, Saucier N, Rizzi EM, Harmon MT, Keppel MP, Ritter M, Similuk M, Kulm E, Joyce M, de Jesus AA, Goldbach-Mansky R, Lee YS, Cella M, Kendall PL, Dinauer MC, Bednarski JJ, Bemrich-Stolz C, Canna SW, Abraham SM, Demczko MM, Powell J, Jones SM, Scurlock AM, De Ravin SS, Bleesing JJ, Connelly JA, Rao VK, Schuettpelz LG, Cooper MA
Blood 2021 May 6;137(18):2450-2462. doi: 10.1182/blood.2020009620. PMID: 33512449Free PMC Article
Kimble DC, Lach FP, Gregg SQ, Donovan FX, Flynn EK, Kamat A, Young A, Vemulapalli M, Thomas JW, Mullikin JC, Auerbach AD, Smogorzewska A, Chandrasekharappa SC
Hum Mutat 2018 Feb;39(2):237-254. Epub 2017 Nov 22 doi: 10.1002/humu.23366. PMID: 29098742Free PMC Article
Scheinberg P, Nunez O, Weinstein B, Scheinberg P, Biancotto A, Wu CO, Young NS
N Engl J Med 2011 Aug 4;365(5):430-8. doi: 10.1056/NEJMoa1103975. PMID: 21812672Free PMC Article

Diagnosis

Wlodarski MW, Vlachos A, Farrar JE, Da Costa LM, Kattamis A, Dianzani I, Belendez C, Unal S, Tamary H, Pasauliene R, Pospisilova D, de la Fuente J, Iskander D, Wolfe L, Liu JM, Shimamura A, Albrecht K, Lausen B, Bechensteen AG, Tedgard U, Puzik A, Quarello P, Ramenghi U, Bartels M, Hengartner H, Farah RA, Al Saleh M, Hamidieh AA, Yang W, Ito E, Kook H, Ovsyannikova G, Kager L, Gleizes PE, Dalle JH, Strahm B, Niemeyer CM, Lipton JM, Leblanc TM; international Diamond-Blackfan anaemia syndrome guideline panel
Lancet Haematol 2024 May;11(5):e368-e382. doi: 10.1016/S2352-3026(24)00063-2. PMID: 38697731
Chisholm KM, Bohling SD
Clin Lab Med 2023 Dec;43(4):639-655. Epub 2023 Aug 7 doi: 10.1016/j.cll.2023.06.005. PMID: 37865508
Alshaibani A, Dufour C, Risitano A, de Latour R, Aljurf M
Hematol Oncol Stem Cell Ther 2022 Jun 1;15(2):8-12. doi: 10.1016/j.hemonc.2020.10.001. PMID: 33197413
DeZern AE, Churpek JE
Blood Adv 2021 Jun 22;5(12):2660-2671. doi: 10.1182/bloodadvances.2021004345. PMID: 34156438Free PMC Article
Aluri J, Bach A, Kaviany S, Chiquetto Paracatu L, Kitcharoensakkul M, Walkiewicz MA, Putnam CD, Shinawi M, Saucier N, Rizzi EM, Harmon MT, Keppel MP, Ritter M, Similuk M, Kulm E, Joyce M, de Jesus AA, Goldbach-Mansky R, Lee YS, Cella M, Kendall PL, Dinauer MC, Bednarski JJ, Bemrich-Stolz C, Canna SW, Abraham SM, Demczko MM, Powell J, Jones SM, Scurlock AM, De Ravin SS, Bleesing JJ, Connelly JA, Rao VK, Schuettpelz LG, Cooper MA
Blood 2021 May 6;137(18):2450-2462. doi: 10.1182/blood.2020009620. PMID: 33512449Free PMC Article

Therapy

Ji J, Wan Z, Ruan J, Yang Y, Hu Q, Chen Z, Yang C, Chen M, Han B
Blood Cancer J 2023 Sep 19;13(1):146. doi: 10.1038/s41408-023-00921-8. PMID: 37726286Free PMC Article
Gonnot M, Neumann F, Huet F, Maudinas R, Leblanc T, Lacaille F
J Pediatr Gastroenterol Nutr 2022 Nov 1;75(5):553-555. Epub 2022 Sep 6 doi: 10.1097/MPG.0000000000003603. PMID: 36070526
DeZern AE, Eapen M, Wu J, Talano JA, Solh M, Dávila Saldaña BJ, Karanes C, Horwitz ME, Mallhi K, Arai S, Farhadfar N, Hexner E, Westervelt P, Antin JH, Deeg HJ, Leifer E, Brodsky RA, Logan BR, Horowitz MM, Jones RJ, Pulsipher MA
Lancet Haematol 2022 Sep;9(9):e660-e669. Epub 2022 Jul 27 doi: 10.1016/S2352-3026(22)00206-X. PMID: 35907408Free PMC Article
Alshaibani A, Dufour C, Risitano A, de Latour R, Aljurf M
Hematol Oncol Stem Cell Ther 2022 Jun 1;15(2):8-12. doi: 10.1016/j.hemonc.2020.10.001. PMID: 33197413
Scheinberg P, Nunez O, Weinstein B, Scheinberg P, Biancotto A, Wu CO, Young NS
N Engl J Med 2011 Aug 4;365(5):430-8. doi: 10.1056/NEJMoa1103975. PMID: 21812672Free PMC Article

Prognosis

DeZern AE, Churpek JE
Blood Adv 2021 Jun 22;5(12):2660-2671. doi: 10.1182/bloodadvances.2021004345. PMID: 34156438Free PMC Article
Aluri J, Bach A, Kaviany S, Chiquetto Paracatu L, Kitcharoensakkul M, Walkiewicz MA, Putnam CD, Shinawi M, Saucier N, Rizzi EM, Harmon MT, Keppel MP, Ritter M, Similuk M, Kulm E, Joyce M, de Jesus AA, Goldbach-Mansky R, Lee YS, Cella M, Kendall PL, Dinauer MC, Bednarski JJ, Bemrich-Stolz C, Canna SW, Abraham SM, Demczko MM, Powell J, Jones SM, Scurlock AM, De Ravin SS, Bleesing JJ, Connelly JA, Rao VK, Schuettpelz LG, Cooper MA
Blood 2021 May 6;137(18):2450-2462. doi: 10.1182/blood.2020009620. PMID: 33512449Free PMC Article
Karremann M, Neumaier-Probst E, Schlichtenbrede F, Beier F, Brümmendorf TH, Cremer FW, Bader P, Dürken M
Orphanet J Rare Dis 2020 Oct 23;15(1):299. doi: 10.1186/s13023-020-01553-y. PMID: 33097095Free PMC Article
Renaghan AD, Jaimes EA, Malyszko J, Perazella MA, Sprangers B, Rosner MH
Clin J Am Soc Nephrol 2020 Feb 7;15(2):289-297. Epub 2019 Dec 13 doi: 10.2215/CJN.08580719. PMID: 31836598Free PMC Article
Scheinberg P, Nunez O, Weinstein B, Scheinberg P, Biancotto A, Wu CO, Young NS
N Engl J Med 2011 Aug 4;365(5):430-8. doi: 10.1056/NEJMoa1103975. PMID: 21812672Free PMC Article

Clinical prediction guides

Chatzikalil E, Kattamis A, Diamantopoulos P, Solomou EE
Int J Hematol 2023 Dec;118(6):667-681. Epub 2023 Sep 28 doi: 10.1007/s12185-023-03666-z. PMID: 37768509
Gurnari C, Pagliuca S, Prata PH, Galimard JE, Catto LFB, Larcher L, Sebert M, Allain V, Patel BJ, Durmaz A, Pinto AL, Inacio MCB, Hernandez L, Dhedin N, Caillat-Zucman S, Clappier E, Sicre de Fontbrune F, Voso MT, Visconte V, Peffault de Latour R, Soulier J, Calado RT, Socié G, Maciejewski JP
J Clin Oncol 2023 Jan 1;41(1):132-142. Epub 2022 Sep 2 doi: 10.1200/JCO.22.00710. PMID: 36054881Free PMC Article
Alshaibani A, Dufour C, Risitano A, de Latour R, Aljurf M
Hematol Oncol Stem Cell Ther 2022 Jun 1;15(2):8-12. doi: 10.1016/j.hemonc.2020.10.001. PMID: 33197413
Ulirsch JC, Verboon JM, Kazerounian S, Guo MH, Yuan D, Ludwig LS, Handsaker RE, Abdulhay NJ, Fiorini C, Genovese G, Lim ET, Cheng A, Cummings BB, Chao KR, Beggs AH, Genetti CA, Sieff CA, Newburger PE, Niewiadomska E, Matysiak M, Vlachos A, Lipton JM, Atsidaftos E, Glader B, Narla A, Gleizes PE, O'Donohue MF, Montel-Lehry N, Amor DJ, McCarroll SA, O'Donnell-Luria AH, Gupta N, Gabriel SB, MacArthur DG, Lander ES, Lek M, Da Costa L, Nathan DG, Korostelev AA, Do R, Sankaran VG, Gazda HT
Am J Hum Genet 2018 Dec 6;103(6):930-947. Epub 2018 Nov 29 doi: 10.1016/j.ajhg.2018.10.027. PMID: 30503522Free PMC Article
Scheinberg P, Nunez O, Weinstein B, Scheinberg P, Biancotto A, Wu CO, Young NS
N Engl J Med 2011 Aug 4;365(5):430-8. doi: 10.1056/NEJMoa1103975. PMID: 21812672Free PMC Article

Recent systematic reviews

Zhang Y, Li J, Li X, Geng Q, Xie Y, Zhang G, Wei M, Ma Y
Syst Rev 2024 Apr 4;13(1):101. doi: 10.1186/s13643-024-02515-2. PMID: 38576005Free PMC Article
Guo H, Liu C, Kang L, Liu C, Liu Y
Hematology 2024 Dec;29(1):2335419. Epub 2024 Mar 30 doi: 10.1080/16078454.2024.2335419. PMID: 38553907
Santana NCM, de Sena ACVP, Rocha PADS, de Arruda JAA, Torres-Pereira CC, Abreu LG, Fournier BPJ, Warnakulasuriya S, Silva TA
Oral Oncol 2024 Mar;150:106699. Epub 2024 Feb 3 doi: 10.1016/j.oraloncology.2024.106699. PMID: 38309198
ElGohary G, El Fakih R, de Latour R, Risitano A, Marsh J, Schrezenmeier H, Gluckman E, Höchsmann B, Pierri F, Halkes C, Alzahrani H, De la Fuente J, Cesaro S, Alahmari A, Ahmed SO, Passweg J, Dufour C, Bacigalupo A, Aljurf M
Bone Marrow Transplant 2020 Oct;55(10):1906-1917. Epub 2020 Apr 28 doi: 10.1038/s41409-020-0897-2. PMID: 32346079
Malouf R, Ashraf A, Hadjinicolaou AV, Doree C, Hopewell S, Estcourt LJ
Cochrane Database Syst Rev 2018 May 14;5(5):CD012342. doi: 10.1002/14651858.CD012342.pub2. PMID: 29758592Free PMC Article

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