Approach Considerations

Bloom syndrome should be suspected if any of the clinical or cytogenetic criteria described below are found.^[47]

Clinical findings are as follows:

Prenatal-onset retarded growth that usually includes weight gain, linear growth, and head circumference and that persists into infancy, childhood, and adulthood
Moderate-to-severe growth retardation together with photosensitive erythematous rash that commonly involves the face in a butterfly distribution
Moderate-to-severe growth retardation and an early diagnosis of cancer

Cytogenetic findings are as follows:

Increased numbers of sister-chromatid exchanges
Increased quadriradial configurations (Qrs) in cultured blood lymphocytes
Chromatid gaps, breaks, and rearrangements

Laboratory Studies

The diagnosis of Bloom syndrome (congenital telangiectatic erythema) can be confirmed or excluded by a laboratory test known as a chromosome study; blood and skin cells show a characteristic pattern of chromosome breakage and rearrangement. Testing for chromosome instability, including the presence of quadriradicals and increased sister chromatid exchanges, is performed at the US National Institutes of Health and US Armed Forces Institute of Pathology laboratories.

Prenatal diagnosis

Prenatal diagnosis of Bloom syndrome is possible with amniocentesis for amniotic fluid cell culture to assess for a high number of sister chromatid exchanges; DNA analysis will be available in the near future.

Genetic screening and counseling

Genetic screening is recommended for populations at high risk for being a carrier of the disease, such as Ashkenazi Jews. Targeted mutation analysis and polymerase chain reaction (PCR) to examine the DNA for the BLM 6-deletion/7-insertion mutation should be performed.

Genetic counseling could be offered to parents of patients with Bloom syndrome. Being an autosomal recessive disease in its mode of transmission, the risk of having the disease in siblings of heterozygous carriers is estimated to be 25%.^[48]

Screening for complications

Immunoglobulin levels should be checked; decreased immunoglobulin A and immunoglobulin M, with or without immunoglobulin G changes, are expected.

There is no consensus regarding cancer surveillance in Bloom syndrome patients. The most important recommendation is to observe Bloom syndrome patients for any signs and symptoms that warrant further investigations (eg, complete blood cell count with any constitutional symptoms). Unintentional weight loss should be investigated thoroughly. Screening colonoscopy could be considered from age 16 years and carried out regularly, but there is no consensus for the appropriate interval.^[38]

Periodic evaluation for leukemia and early screening for breast, cervical, and colorectal cancers are recommended. MRI and ultrasonography are recommended rather than other radiologic diagnostic modalities, in order to minimize the exposure to radiation in such vulnerable patients.

Other Tests

See the Workup section in the Medscape article Short Stature for detailed information on the workup for short stature.

Evaluation of children with photosensitivity

Phototesting and photopatch testing could be performed. Screening for antinuclear antibodies (ANA) and performing a porphyrin profile to exclude the possibility of lupus erythematosus or erythropoietic porphyria may be warranted.

Skin biopsy

Histopathologic findings from skin biopsies taken from the erythematous lesions show a lupuslike picture: follicular plugging, interface dermatitis, monocellular infiltrate, and perivascular infiltrate. However, the presence of changes in the basement membrane, periadnexal lymphocytic infiltration, and dermal mucin are very rare.^[46]Bandlike dense lymphoid infiltrates with epidermotropism, resembling mycosis fungoides, have been reported.

Treatment & Management

Bloom D. Congenital telangiectatic erythema resembling lupus erythematosus in dwarfs; probably a syndrome entity. AMA Am J Dis Child. 1954 Dec. 88(6):754-8. [QxMD MEDLINE Link].
Straughen J, Ciocci S, Ye TZ, et al. Physical mapping of the bloom syndrome region by the identification of YAC and P1 clones from human chromosome 15 band q26.1. Genomics. 1996 Jul 1. 35(1):118-28. [QxMD MEDLINE Link].
Park CJ, Ko J, Ryu KS, Choi BS. Solution structure of the RecQ C-terminal domain of human Bloom syndrome protein. J Biomol NMR. 2014 Feb. 58(2):141-7. [QxMD MEDLINE Link].
Kim SY, Hakoshima T, Kitano K. Structure of the RecQ C-terminal domain of human Bloom syndrome protein. Sci Rep. 2013 Nov 21. 3:3294. [QxMD MEDLINE Link].
Salah GB, Salem IH, Masmoudi A, Rhouma BB, Turki H, Fakhfakh F, et al. Chromosomal instability associated with a novel BLM frameshift mutation (c.1980-1982delAA) in two unrelated Tunisian families with Bloom syndrome. J Eur Acad Dermatol Venereol. 2014 Oct. 28(10):1318-23. [QxMD MEDLINE Link].
Payne M, Hickson ID. Genomic instability and cancer: lessons from analysis of Bloom's syndrome. Biochem Soc Trans. 2009 Jun. 37:553-9. [QxMD MEDLINE Link].
Seki M, Nakagawa T, Seki T, et al. Bloom helicase and DNA topoisomerase IIIalpha are involved in the dissolution of sister chromatids. Mol Cell Biol. 2006 Aug. 26(16):6299-307. [QxMD MEDLINE Link].
LaRocque JR, Stark JM, Oh J, Bojilova E, Yusa K, Horie K, et al. Interhomolog recombination and loss of heterozygosity in wild-type and Bloom syndrome helicase (BLM)-deficient mammalian cells. Proc Natl Acad Sci U S A. 2011 Jul 19. 108(29):11971-6. [QxMD MEDLINE Link]. [Full Text].
Aguilera A, Gómez-González B. Genome instability: a mechanistic view of its causes and consequences. Nat Rev Genet. 2008 Mar. 9 (3):204-17. [QxMD MEDLINE Link].
Risch N, Tang H, Katzenstein H, Ekstein J. Geographic distribution of disease mutations in the Ashkenazi Jewish population supports genetic drift over selection. Am J Hum Genet. 2003 Apr. 72(4):812-22. [QxMD MEDLINE Link]. [Full Text].
Nicotera TM, Notaro J, Notaro S, Schumer J, Sandberg AA. Elevated superoxide dismutase in Bloom's syndrome: a genetic condition of oxidative stress. Cancer Res. 1989 Oct 1. 49(19):5239-43. [QxMD MEDLINE Link].
Deans AJ, West SC. FANCM connects the genome instability disorders Bloom's Syndrome and Fanconi Anemia. Mol Cell. 2009 Dec 25. 36(6):943-53. [QxMD MEDLINE Link].
Guo R, Xu D, Wang W. Identification and analysis of new proteins involved in the DNA damage response network of Fanconi anemia and Bloom syndrome. Methods. 2009 May. 48(1):72-9. [QxMD MEDLINE Link]. [Full Text].
Bugreev DV, Mazina OM, Mazin AV. Bloom syndrome helicase stimulates RAD51 DNA strand exchange activity through a novel mechanism. J Biol Chem. 2009 Sep 25. 284(39):26349-59. [QxMD MEDLINE Link]. [Full Text].
Zbinden I, Cerutti P. Near-ultraviolet sensitivity of skin fibroblasts of patients with Bloom's syndrome. Biochem Biophys Res Commun. 1981 Feb 12. 98(3):579-87. [QxMD MEDLINE Link].
Lehmann AR, Kirk-Bell S, Arlett CF, Paterson MC, Lohman PH, de Weerd-Kastelein EA, et al. Xeroderma pigmentosum cells with normal levels of excision repair have a defect in DNA synthesis after UV-irradiation. Proc Natl Acad Sci U S A. 1975 Jan. 72(1):219-23. [QxMD MEDLINE Link]. [Full Text].
Hütteroth TH, Litwin SD, German J. Abnormal immune responses of Bloom's syndrome lymphocytes in vitro. J Clin Invest. 1975 Jul. 56(1):1-7. [QxMD MEDLINE Link]. [Full Text].
Garcia AM, Salomon RN, Witsell A, Liepkalns J, Calder RB, Lee M, et al. Loss of the Bloom Syndrome helicase increases DNA ligase 4-independent genome rearrangements and tumorigenesis in aging Drosophila. Genome Biol. 2011 Dec 19. 12(12):R121. [QxMD MEDLINE Link].
Li L, Eng C, Desnick RJ, German J, Ellis NA. Carrier frequency of the Bloom syndrome blmAsh mutation in the Ashkenazi Jewish population. Mol Genet Metab. 1998 Aug. 64(4):286-90. [QxMD MEDLINE Link].
Weill Cornell Medical College, Bloom’s Syndrome Registry. A Concise Clinical Description of Bloom’s Syndrome. Available at http://weill.cornell.edu/bsr/clinical_description/. 2009; Accessed: February 16, 2017.
Kaneko H, Inoue R, Fukao T, Kasahara K, Tashita H, Teramoto T, et al. Two Japanese siblings with Bloom syndrome gene mutation and B-cell lymphoma. Leuk Lymphoma. 1997 Nov. 27(5-6):539-42. [QxMD MEDLINE Link].
Keller C, Keller KR, Shew SB, Plon SE. Growth deficiency and malnutrition in Bloom syndrome. J Pediatr. 1999 Apr. 134 (4):472-9. [QxMD MEDLINE Link].
Passarge E. Bloom’s syndrome. German J, ed. Chromosome Mutation and Neoplasia. New York, NY: Alan R. Liss; 1983. 11–21.
Diaz A, Vogiatzi MG, Sanz MM, German J. Evaluation of short stature, carbohydrate metabolism and other endocrinopathies in Bloom's syndrome. Horm Res. 2006. 66 (3):111-7. [QxMD MEDLINE Link].
Chavez-Alvarez S, Villarreal-Martinez A, Velasco-Campos MDR, Moreno-Vega I, Martinez-de-Villarreal LE, Herz-Ruelas M, et al. Bloom syndrome sans characteristic facial features in a Mestizo patient- a diagnostic challenge. Indian J Dermatol Venereol Leprol. 2019 Jan-Feb. 85 (1):130. [QxMD MEDLINE Link].
Arora H, Chacon AH, Choudhary S, McLeod MP, Meshkov L, Nouri K, et al. Bloom syndrome. Int J Dermatol. 2014 Jul. 53 (7):798-802. [QxMD MEDLINE Link].
Jian-Bing W, Cheng-Rang L, Yi-Ping M, Nan S, Hui L, Lin L. A case of Bloom syndrome with uncommon clinical manifestations confirmed on genetic testing. Cutis. 2016 Feb. 97 (2):E10-3. [QxMD MEDLINE Link].
Vojtková J, Čiljaková M, Jeseňák M, Mišovicová N, Bánovčin P. Bloom syndrome without typical sun-sensitive skin lesions in three Slovak siblings. Int J Dermatol. 2015 Sep 4. [QxMD MEDLINE Link].
Vojtková J, Čiljaková M, Jeseňák M, Mišovicová N, Bánovčin P. Bloom syndrome without typical sun-sensitive skin lesions in three Slovak siblings. Int J Dermatol. 2016 Jun. 55 (6):687-690. [QxMD MEDLINE Link].
Masmoudi A, Marrakchi S, Kamoun H, Chaaben H, Ben Salah G, Ben Salah R, et al. Clinical and laboratory findings in 8 patients with Bloom's syndrome. J Dermatol Case Rep. 2012 Mar 27. 6 (1):29-33. [QxMD MEDLINE Link].
Sanz MM, German J, Cunniff C. Pagon RA, Adam MP, Ardinger HH, et al. GeneReviews® [Internet]. Seattle, Wash: University of Washington; April 7, 2016.
Ozawa T, Kondo N, Motoyoshi F, Kasahara K, Orii T. DNA mutation induced in the sequence upstream of the secreted MYU C-terminal coding sequence by ultraviolet irradiation in the cell line of Bloom's syndrome. Eur J Immunogenet. 1995 Apr. 22 (2):163-9. [QxMD MEDLINE Link].
Draznin M, Robles DT, Nguyen V, Berg D. An unusual case of Bloom syndrome presenting with basal cell carcinoma. Dermatol Surg. 2009 Jan. 35 (1):131-4. [QxMD MEDLINE Link].
Bhisitkul RB, Rizen M. Bloom syndrome: multiple retinopathies in a chromosome breakage disorder. Br J Ophthalmol. 2004 Mar. 88(3):354-7. [QxMD MEDLINE Link]. [Full Text].
Aljarad S, Alhamid A, Rahmeh AR, Alibraheem A, Wafa A, Alachkar W, et al. Bloom syndrome with myelodysplastic syndrome that was converted into acute myeloid leukaemia, with new ophthalmologic manifestations: the first report from Syria. Oxf Med Case Reports. 2018 Dec. 2018 (12):omy096. [QxMD MEDLINE Link].
Sultan SJ, Sultan ST. Bloom syndrome in two siblings. Pediatr Dermatol. 2010 Mar-Apr. 27(2):174-7. [QxMD MEDLINE Link].
German J. The immunodeficiency of Bloom syndrome. Ochs HD, Smith CIE, Puck JM, eds. Primary Immunodeficiency Diseases: A Molecular and Genetic Approach. New York, NY: Oxford University Press; 1999. 335.
Cunniff C, Bassetti JA, Ellis NA. Bloom's Syndrome: Clinical Spectrum, Molecular Pathogenesis, and Cancer Predisposition. Mol Syndromol. 2017 Jan. 8 (1):4-23. [QxMD MEDLINE Link].
Amor-Guéret M. Bloom syndrome, genomic instability and cancer: the SOS-like hypothesis. Cancer Lett. 2006 May 8. 236(1):1-12. [QxMD MEDLINE Link].
German J. Bloom's syndrome. XX. The first 100 cancers. Cancer Genet Cytogenet. 1997 Jan. 93 (1):100-6. [QxMD MEDLINE Link].
Gruber SB, Ellis NA, Scott KK, Almog R, Kolachana P, Bonner JD, et al. BLM heterozygosity and the risk of colorectal cancer. Science. 2002 Sep 20. 297 (5589):2013. [QxMD MEDLINE Link].
Prokofyeva D, Bogdanova N, Dubrowinskaja N, Bermisheva M, Takhirova Z, Antonenkova N, et al. Nonsense mutation p.Q548X in BLM, the gene mutated in Bloom's syndrome, is associated with breast cancer in Slavic populations. Breast Cancer Res Treat. 2013 Jan. 137 (2):533-9. [QxMD MEDLINE Link].
Relhan V, Sinha S, Bhatnagar T, Garg VK, Kochhar A. Bloom syndrome with extensive pulmonary involvement in a child. Indian J Dermatol. 2015 Mar-Apr. 60 (2):217. [QxMD MEDLINE Link].
Nair G, Lobo I, Jayalaksmi TK, Uppe A, Jindal S, Chandra A, et al. Bloom syndrome with lung involvement. Lung India. 2009 Jul. 26 (3):92-4. [QxMD MEDLINE Link].
Jian-Bing W, Cheng-Rang L, Yi-Ping M, Nan S, Hui L, Lin L. A case of Bloom syndrome with uncommon clinical manifestations confirmed on genetic testing. Cutis. 2016 Feb. 97 (2):E10-3. [QxMD MEDLINE Link].
McGowan J, Maize J, Cook J. Lupus-Like Histopathology in Bloom Syndrome: Reexamining the Clinical and Histologic Implications of Photosensitivity. Am J Dermatopathol. 2009 Oct 8. [QxMD MEDLINE Link].
Sanz MM, German J, Cunniff C. Bloom's Syndrome. Pagon RA, Adam MP, Ardinger HH, et al, eds. GeneReviews® [Internet]. University of Washington, Seattle; 2006 Mar 22 [Updated 2019].
Arora H, Chacon AH, Choudhary S, McLeod MP, Meshkov L, Nouri K, et al. Bloom syndrome. Int J Dermatol. 2014 Jul. 53(7):798-802. [QxMD MEDLINE Link].
Cunniff C, Djavid AR, Carrubba S, Cohen B, Ellis NA, Levy CF, et al. Health supervision for people with Bloom syndrome. Am J Med Genet A. 2018 Sep. 176 (9):1872-1881. [QxMD MEDLINE Link].
Thomas ER, Shanley S, Walker L, Eeles R. Surveillance and treatment of malignancy in Bloom syndrome. Clin Oncol (R Coll Radiol). 2008 Jun. 20(5):375-9. [QxMD MEDLINE Link].
Karalis A, Tischkowitz M, Millington GW. Dermatological manifestations of inherited cancer syndromes in children. Br J Dermatol. 2011 Feb. 164 (2):245-56. [QxMD MEDLINE Link].
Oto S, Miyamoto S, Kudoh F, Horie H, Kinugawa N, Okimoto Y. Treatment for B-cell-type lymphoma in a girl associated with Bloom's syndrome. Clin Genet. 1992 Jan. 41 (1):46-50. [QxMD MEDLINE Link].
Jastaniah W. Successful treatment of mature B-cell lymphoma with rituximab-based chemotherapy in a patient with Bloom syndrome. Pediatr Blood Cancer. 2016 Dec 14. [QxMD MEDLINE Link].
Chisholm CA, Bray MJ, Karns LB. Successful pregnancy in a woman with Bloom syndrome. Am J Med Genet. 2001 Aug 1. 102(2):136-8. [QxMD MEDLINE Link].

Media Gallery

Crystal structure of the Bloom syndrome helicase BLM in complex with DNA (PDB ID: 4CGZ). Courtesy of Arthur Zalevsky (own work), via Wikimedia Commons.

of 1

Author

Amira M Elbendary, MD, MBBCh, MSc Visiting Dermatopathology Fellow, Ackerman Academy of Dermatopathology; Lecturer, Department of Dermatology, Kasr Alainy University Hospitals, Cairo University, Egypt

Amira M Elbendary, MD, MBBCh, MSc is a member of the following medical societies: Bloom’s Syndrome Association, Egyptian Medical Syndicate, International Dermoscopy Society, Medical Dermatology Society

Disclosure: Nothing to disclose.

Coauthor(s)

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Van Perry, MD Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Additional Contributors

Eleanor E Sahn, MD Director, Division of Pediatric Dermatology, Associate Professor, Departments of Dermatology and Pediatrics, Medical University of South Carolina

Eleanor E Sahn, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Southern Medical Association

Disclosure: Nothing to disclose.

Acknowledgements

Amir A Bajoghli, MD Clinical Assistant Professor of Dermatology, George Washington University School of Medicine and Georgetown University; Chief, Dermatology and Mohs Surgery Section, Inova Fairfax Hospital; Dermatologist, Skin and Laser Surgery Center, PC

Amir A Bajoghli, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, and Massachusetts Medical Society

Disclosure: Nothing to disclose.