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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="Bloom Syndrome" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2023/10/12" /><meta name="citation_author" content="Katherine Langer" /><meta name="citation_author" content="Christopher M Cunniff" /><meta name="citation_author" content="Nicole Kucine" /><meta name="citation_pmid" content="20301572" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK1398/" /><meta name="citation_keywords" content="RecQ-like DNA helicase BLM" /><meta name="citation_keywords" content="BLM" /><meta name="citation_keywords" content="Bloom Syndrome" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Bloom Syndrome" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Katherine Langer" /><meta name="DC.Contributor" content="Christopher M Cunniff" /><meta name="DC.Contributor" content="Nicole Kucine" /><meta name="DC.Date" content="2023/10/12" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK1398/" /><meta name="description" content="Bloom syndrome (BSyn) is characterized by severe pre- and postnatal growth deficiency, immune abnormalities, sensitivity to sunlight, insulin resistance, and a high risk for many cancers that occur at an early age. 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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="All GeneReviews" href="/books/n/gene/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" alt="Cover of GeneReviews®" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>GeneReviews<sup>®</sup> [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK1398_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK1398_dtls__"><div>Adam MP, Feldman J, Mirzaa GM, et al., editors.</div><div>Seattle (WA): <a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>; 1993-2025.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/gene/">GeneReviews by Title</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/gene/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search GeneReviews" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search GeneReviews" submit="false" style="padding: 0.1em 0.4em;" /></div></form><div><ul class="inline_list"><li><a href="/books/n/gene/advanced/">GeneReviews Advanced Search</a></li><li style="margin-left:.5em"><a href="/books/n/gene/helpadvsearch/">Help</a></li></ul></div></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/gene/bpes/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/bohring-opitz/" title="Next page in this title">Next ></a></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK1398_"><span class="title" itemprop="name">Bloom Syndrome</span></h1><p class="contrib-group"><span itemprop="author">Katherine Langer</span>, BA, <span itemprop="author">Christopher M Cunniff</span>, MD, FACMG, and <span itemprop="author">Nicole Kucine</span>, MD, MS.</p><a data-jig="ncbitoggler" href="#__NBK1398_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK1398_ai__"><div class="contrib half_rhythm"><span itemprop="author">Katherine Langer</span>, BA<div class="affiliation small">Department of Pediatrics<br />Weill Cornell Medicine<br />New York, New York<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.llenroc.dem@2004ljk" class="oemail">ude.llenroc.dem@2004ljk</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Christopher M Cunniff</span>, MD, FACMG<div class="affiliation small">Department of Pediatrics<br />Weill Cornell Medicine<br />New York, New York<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.llenroc.dem@9309cmc" class="oemail">ude.llenroc.dem@9309cmc</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Nicole Kucine</span>, MD, MS<div class="affiliation small">Department of Pediatrics<br />Weill Cornell Medicine<br />New York, New York<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.llenroc.dem@5109kin" class="oemail">ude.llenroc.dem@5109kin</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">March 22, 2006</span>; Last Update: <span itemprop="dateModified">October 12, 2023</span>.</p><p><em>Estimated reading time: 27 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="bloom.Summary" itemprop="description"><h2 id="_bloom_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Bloom syndrome (BSyn) is characterized by severe pre- and postnatal growth deficiency, immune abnormalities, sensitivity to sunlight, insulin resistance, and a high risk for many cancers that occur at an early age. Despite their very small head circumference, most affected individuals have normal intellectual ability. Women may be fertile but often have early menopause, and men tend to be infertile, with only one confirmed case of paternity. Serious medical complications that are more common than in the general population and that also appear at unusually early ages include cancer of a wide variety of types and anatomic sites, diabetes mellitus as a result of insulin resistance, chronic obstructive pulmonary disease, and hypothyroidism.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of BSyn is established in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with characteristic clinical features and <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic variants in <i>BLM</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Increased-calorie-density formulas and foods may promote weight gain; consultation with gastroenterologist or feeding specialist and treatment for gastroesophageal reflux disease as needed; standard dietary treatment for dyslipidemia. Skin protection, including avoiding excessive sun exposure, sun-protective clothing and broad-brimmed hat, UV-blocking sunglasses, and use of broad-spectrum sunscreen with SPF of at least 30; standard treatment of skin cancers. Individuals with recurrent infections and defects in humoral immunity may be treated with immunoglobulins to decrease frequency and severity of infections. Developmental services and educational support as needed. In persons with cancer, modification of chemotherapy dosage and duration per oncologist. Fertility treatments as needed; standard treatment of diabetes mellitus and hypothyroidism. Cough assist devices, vibration vests, and daily nasal lavage for mucociliary clearance for bronchiectasis.</p><p><i>Surveillance:</i> Monitor growth, feeding, and for gastroesophageal reflux at each visit throughout childhood; annual lipid profile beginning at age ten years. Skin exam with a dermatologist upon recognition of suspicious skin lesions and annually thereafter. Assess for recurrent, severe, or opportunistic infections at each visit. Developmental, neurobehavioral, and psychological assessment as needed. Clinical assessment for hematuria and/or abdominal mass and abdominal ultrasound examination every three months until age eight years for Wilms tumor. Screening and family education regarding signs and symptoms of leukemia and lymphoma at every health visit. Whole-body MRI every one to two years beginning at age 12 to 13 years for risk of lymphoma. Annual colonoscopy beginning at age ten to 12 years. Fecal immunochemical testing every six months beginning at age ten to 12 years. Annual breast MRI in women beginning at age 18 years. Annual fasting blood glucose and hemoglobin A1c beginning at age ten years. Annual serum TSH with reflex to thyroxine beginning at age ten years. Assess for recurrent and/or chronic pulmonary disease at each visit.</p><p><i>Agents/circumstances to avoid:</i> Sun exposure to the face and other exposed skin, particularly in infancy and early childhood, should be avoided. Exposure to ionizing radiation should be minimized. Dose reductions and shortened courses of chemotherapy when needed to avoid significant side effects and toxicity (including secondary malignancies). Alkylating agents and radiation therapy are considered high risk and are avoided when possible in those with BSyn.</p><p><i>Evaluation of relatives at risk:</i> It is appropriate to evaluate sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> in order to identify as early as possible those who would benefit from avoidance of sun exposure and early surveillance for cancer.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>BSyn is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner. If both parents are known to be <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for a <i>BLM</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, each sib of an affected individual has at conception a 25% chance of inheriting <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic variants and being affected, a 50% chance of being a <a class="def" href="/books/n/gene/glossary/def-item/heterozygote/">heterozygote</a> (<a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>), and a 25% chance of inheriting neither of the <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> pathogenic variants. Heterozygotes (carriers) are not at risk of developing BSyn; the cancer risk of heterozygotes as a group remains unclear. Once the <i>BLM</i> pathogenic variants have been identified in an affected family member, prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible. BSyn is included on most expanded carrier screening panels.</p></div></div><div id="bloom.Diagnosis"><h2 id="_bloom_Diagnosis_">Diagnosis</h2><div id="bloom.Suggestive_Findings"><h3>Suggestive Findings</h3><p>Bloom syndrome (BSyn) <b>should be suspected</b> in an individual with any of the following clinical or <a class="def" href="/books/n/gene/glossary/def-item/cytogenetic/">cytogenetic</a> findings.</p><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>Prenatal-onset growth deficiency that usually affects linear growth, weight gain, and head circumference and that persists into infancy, childhood, and adulthood</div></li><li class="half_rhythm"><div>Moderate-to-severe growth deficiency and a sun-sensitive, erythematous rash that commonly involves the face and appears in a butterfly distribution</div></li><li class="half_rhythm"><div>Moderate-to-severe growth deficiency and a diagnosis of cancer, usually occurring at an earlier age than in the general population</div></li></ul><p><b>Cytogenetic findings.</b> Increased numbers of sister-chromatid exchanges (SCEs)</p></div><div id="bloom.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of BSyn <b>is established</b> in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic (or <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>) variants in <i>BLM</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK1398/table/bloom.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figobbloomTmoleculargenetictestingusedi">Table 1</a>).</p><p>Note: (1) An increased frequency of SCEs on specialized <a class="def" href="/books/n/gene/glossary/def-item/cytogenetic/">cytogenetic</a> studies may be helpful in circumstances where <i>BLM</i> variant analysis is inconclusive. SCE analysis alone is not sufficient to confirm a diagnosis of BSyn because increased SCEs are also observed in persons with <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic variants in <i>RMI1</i>, <i>RMI2</i>, and <i>TOP3A</i> [<a class="bk_pop" href="#bloom.REF.hudson.2016.e1006483">Hudson et al 2016</a>, <a class="bk_pop" href="#bloom.REF.martin.2018.221">Martin et al 2018</a>]. (2) Per ACMG/AMP variant interpretation guidelines, the terms "<a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>" and "<a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a> variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [<a class="bk_pop" href="#bloom.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this <i>GeneReview</i> is understood to include likely pathogenic variants. (3) Identification of biallelic variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> (or of one known pathogenic variant and one variant of uncertain significance) does not establish or rule out the diagnosis.</p><p>Molecular genetic testing approaches can include a combination of <b><a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted testing</b> (single gene testing, <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a>) and <b>comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> (<a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a>, <a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a>). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved (see <a href="#bloom.Option_1">Option 1</a>), whereas comprehensive genomic testing does not (see <a href="#bloom.Option_2">Option 2</a>).</p><div id="bloom.Option_1"><h4>Option 1</h4><p><b>Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing.</b> Sequence analysis of <i>BLM</i> is performed first to detect <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants and small intragenic deletions/insertions. Note: Depending on the sequencing method used, single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a>, multiexon, or whole-gene deletions/duplications may not be detected. If only one or no variant is detected by the sequencing method used, the next step is to perform gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> to detect exon and whole-gene deletions or duplications.</p><p><b>A <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>BLM</i> and other genes of interest (see <a href="#bloom.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> and pathogenic variants in genes that do not explain the underlying <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. Note: (1) The genes included in the panel and the diagnostic <a class="def" href="/books/n/gene/glossary/def-item/sensitivity/">sensitivity</a> of the testing used for each <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused <a class="def" href="/books/n/gene/glossary/def-item/exome/">exome</a> analysis that includes genes specified by the clinician. (4) Methods used in a panel may include <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>, and/or other non-sequencing-based tests.</p><p>For an introduction to multigene panels click <a href="/books/n/gene/app5/#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/#app5.Multigene_Panels_FAQs">here</a>.</p></div><div id="bloom.Option_2"><h4>Option 2</h4><p><b>Comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> does not require the clinician to determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> is likely involved. <b>Exome sequencing</b> is most commonly used; <b><a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a></b> is also possible.</p><p>For an introduction to comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing click <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div id="bloom.T.molecular_genetic_testing_used_i" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Bloom Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1398/table/bloom.T.molecular_genetic_testing_used_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__bloom.T.molecular_genetic_testing_used_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_bloom.T.molecular_genetic_testing_used_i_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_bloom.T.molecular_genetic_testing_used_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_bloom.T.molecular_genetic_testing_used_i_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of Pathogenic Variants <sup>2</sup> Identified by Method</th></tr></thead><tbody><tr><td headers="hd_h_bloom.T.molecular_genetic_testing_used_i_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>BLM</i>
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</td><td headers="hd_h_bloom.T.molecular_genetic_testing_used_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>4</sup></td><td headers="hd_h_bloom.T.molecular_genetic_testing_used_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">96%-97% <sup>3</sup></td></tr><tr><td headers="hd_h_bloom.T.molecular_genetic_testing_used_i_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> <sup>5</sup></td><td headers="hd_h_bloom.T.molecular_genetic_testing_used_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3%-4% <sup>3</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="bloom.TF.1.1"><p class="no_margin">See <a href="/books/NBK1398/#bloom.molgen.TA">Table A. Genes and Databases</a> for <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> and protein.</p></div></dd><dt>2. </dt><dd><div id="bloom.TF.1.2"><p class="no_margin">See <a href="#bloom.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>.</p></div></dd><dt>3. </dt><dd><div id="bloom.TF.1.3"><p class="no_margin">See <a href="https://pediatrics.weill.cornell.edu/research/bloom-syndrome-registry" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Bloom Syndrome Registry</a>.</p></div></dd><dt>4. </dt><dd><div id="bloom.TF.1.4"><p class="no_margin">Sequence analysis detects variants that are benign, <a class="def" href="/books/n/gene/glossary/def-item/likely-benign/">likely benign</a>, of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a>, <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>, or pathogenic. Variants may include <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants and small intragenic deletions/insertions; typically, <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> or whole-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions/duplications are not detected. For issues to consider in interpretation of <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> results, click <a href="/books/n/gene/app2/">here</a>.</p></div></dd><dt>5. </dt><dd><div id="bloom.TF.1.5"><p class="no_margin">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> detects intragenic deletions or duplications. Methods used may include a range of techniques such as <a class="def" href="/books/n/gene/glossary/def-item/quantitative-pcr/">quantitative PCR</a>, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted microarray designed to detect single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications.</p></div></dd></dl></div></div></div></div><div id="bloom.Other_Testing"><h4>Other Testing</h4><p><b>Sister-chromatid exchanges (SCEs).</b> Individuals with BSyn have a mean of 40-100 SCEs per metaphase (normal SCEs: <10 per metaphase). Increased frequency of SCEs is demonstrable in BSyn cultured cells (including lymphocytes, fibroblasts, and amniocytes) allowed to proliferate in a medium containing 5-bromo-2'-deoxyuridine (BrdU). Increased SCEs are not unique to BSyn. Three additional <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> disorders (<i>RMI1-</i>, <i>RMI2-</i>, and <i>TOP3A-</i>related disorders) are associated with increased SCEs and similar clinical findings to individuals with BSyn. SCE analysis may be a useful adjunct for diagnosis of BSyn, in the circumstance where only one <i>BLM</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is identified, and <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> finds no pathogenic variants in <i>RMI1</i>, <i>RMI2</i>, or <i>TOP3A.</i> The presence of increased SCEs alone, however, is not sufficient to confirm the diagnosis of BSyn.</p></div></div></div><div id="bloom.Clinical_Characteristics"><h2 id="_bloom_Clinical_Characteristics_">Clinical Characteristics</h2><div id="bloom.Clinical_Description"><h3>Clinical Description</h3><p>The range of clinical features in persons with Bloom syndrome (BSyn) has been tracked through the <a href="https://pediatrics.weill.cornell.edu/research/bloom-syndrome-registry" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Bloom Syndrome Registry</a>. The clinical and genetic histories have been obtained from registered persons diagnosed between 1954 and 2023, and their clinical courses have been followed [<a class="bk_pop" href="#bloom.REF.german.1989.57">German & Passarge 1989</a>, <a class="bk_pop" href="#bloom.REF.german.1993.393">German 1993</a>, <a class="bk_pop" href="#bloom.REF.german.2002">German & Ellis 2002</a>]. The main clinical features of BSyn are discussed here.</p><p><b>Growth deficiency.</b> The most consistent clinical feature of BSyn seen throughout all stages of life is growth deficiency affecting height, weight, and head circumference. Body proportions are normal.</p><p>The affected fetus is smaller than normal for gestational age. The mean birth weight of affected males is 1,760 g (range: 900-3,189 g) and of affected females, 1,754 g (range: 700-2,892 g). The average adult height of men is 149 cm (range: 128-164 cm) and of women, 138 cm (range: 115-160 cm).</p><p>Plasma growth hormone concentration is normal. Growth hormone therapy has not consistently increased growth rate in most persons, but some have experienced improved linear growth.</p><p>Subcutaneous adipose tissue is sparse throughout childhood and adolescence, but adults may develop central obesity. Providing increased calories in childhood and adolescence does not usually result in substantial changes in growth parameters, particularly linear growth. Studies of small cohorts have shown that supplemental feeding may result in increased fat deposition in individuals with BSyn. In addition, lipid profile abnormalities were identified in five of ten individuals tested [<a class="bk_pop" href="#bloom.REF.diaz.2006.111">Diaz et al 2006</a>].</p><p>Serial measurements of 136 individuals with BSyn (81 male, 55 female) showed that mean head circumference was below normal at all ages [<a class="bk_pop" href="#bloom.REF.keller.1999.472">Keller et al 1999</a>]. The head shape is often described as long and narrow [<a class="bk_pop" href="#bloom.REF.cunniff.2017.4">Cunniff et al 2017</a>].</p><p><b>Feeding problems.</b> Most parents report that feeding is an issue for their newborns, infants, and young children. Many infants have had gastrostomy tubes placed. In a minority of infants with BSyn, nursing and eating are normal. The child with BSyn characteristically eats slowly, has a decreased appetite, and eats a limited variety of foods. Due to poor weight gain, formula and nutritional supplements with increased caloric density are prescribed in infancy and childhood. Despite these maneuvers, weight gain continues to be modest, and children rarely have a normal weight for age. Gastroesophageal reflux is common and may contribute to the feeding issues.</p><p><b>Facial features.</b> The facial appearance of people with BSyn is variable and may be indistinguishable from unaffected persons of similar age and size. More commonly, the face appears narrow, with underdeveloped malar and mandibular prominences and retrognathia or micrognathia (see <a class="figpopup" href="/books/NBK1398/figure/bloom.F1/?report=objectonly" target="object" rid-figpopup="figbloomF1" rid-ob="figobbloomF1">Figure 1</a>). A paucity of subcutaneous fat may cause the nose and/or ears to appear prominent.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figbloomF1" co-legend-rid="figlgndbloomF1"><a href="/books/NBK1398/figure/bloom.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figbloomF1" rid-ob="figobbloomF1"><img class="small-thumb" src="/books/NBK1398/bin/bloom-Image001.gif" src-large="/books/NBK1398/bin/bloom-Image001.jpg" alt="Figure 1. . Individual with Bloom syndrome showing characteristic long, narrow face and erythematous rash." /></a><div class="icnblk_cntnt" id="figlgndbloomF1"><h4 id="bloom.F1"><a href="/books/NBK1398/figure/bloom.F1/?report=objectonly" target="object" rid-ob="figobbloomF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">Individual with Bloom syndrome showing characteristic long, narrow face and erythematous rash. Reproduced with permission from Cunniff et al [2017]</p></div></div><p><b>Skin lesions.</b> The skin at birth and during early infancy appears normal; however, typically following sun exposure during the first or second year of life, a red, sun-sensitive rash appears on the nose and cheeks and sometimes also on the dorsa of the hands and forearms (see <a class="figpopup" href="/books/NBK1398/figure/bloom.F1/?report=objectonly" target="object" rid-figpopup="figbloomF1" rid-ob="figobbloomF1">Figure 1</a>). This rash varies in severity and extent among affected individuals; in some, it is minimal. It is usually characterized by telangiectasia but in others is described as poikiloderma. In severely affected individuals, the lesion can be bright red and can extend onto adjacent areas.</p><p>Additional dermatologic manifestations include cheilitis, blistering and fissuring of the lips, eyebrow and eyelash hair loss, alopecia areata, and vesicular and bullous lesions with excessive or intense sun exposure. Café au lait macules and areas of hypopigmented skin are more numerous and larger than in those without BSyn.</p><p><b>Immunodeficiency.</b> In children and adults who have had laboratory evaluation of their immune system, the concentration of one or more of the plasma immunoglobulins is usually abnormally low. IgM and IgA levels are most commonly affected. Although the numbers of T and B cells are usually normal, variable abnormalities of the adaptive immune system suggest a possible role in the frequent infections reported in affected individuals.</p><p><b>Infections.</b> Parents of children with BSyn report that their affected children have more childhood infections than their sibs and peers; none, however, has had an opportunistic infection, and few persons with BSyn have had bacterial sepsis, meningitis, or pneumonia.</p><p><b>Fertility.</b> Most men with BSyn assessed for infertility have had azoospermia or severe oligospermia. There is, however, one confirmed case of paternity [<a class="bk_pop" href="#bloom.REF.ben_salah.2014.7373">Ben Salah et al 2014</a>]. Women with BSyn, although often fertile, may enter menopause prematurely. Eleven women with BSyn followed in the Bloom Syndrome Registry have become pregnant at least once; seven of them have delivered a total of 11 healthy babies of normal size.</p><p><b>Intelligence.</b> There are no systematic studies of academic achievement or cognitive performance in persons with BSyn. The great majority appear to perform within the normal range of intellectual development. Some have required academic support for attention-related issues and task orientation, but it is not clear that the prevalence of these problems is different from that seen in the general population. Many others have excelled in school, with some earning graduate degrees.</p><p><b>Other clinical features.</b> Major anatomic defects are not increased in frequency. In the 294 persons in the Bloom Syndrome Registry as of 2023, only single examples of the following have occurred: tracheoesophageal fistula, cardiac malformation, absent thumbs, and absence of a toe and malformation of a thumb.</p><p><b>Medical complications</b> of BSyn include cancer, diabetes mellitus, pulmonary disease, and hypothyroidism.</p><p><b>Cancer</b> is the most frequent medical complication and the most common cause of death in individuals with BSyn. Although the wide distribution of cell types and anatomic sites of cancer resemble that in the general population, it occurs more frequently and at much earlier ages in individuals with BSyn. Development of multiple cancers in a single individual is also much more common. <a href="/books/NBK1398/table/bloom.T.malignant_neoplasms_diagnosed_in/?report=objectonly" target="object" rid-ob="figobbloomTmalignantneoplasmsdiagnosedin">Table 2</a> summarizes the 251 malignant neoplasms diagnosed in 155 persons followed in the Bloom Syndrome Registry from 1954 to 2022.</p><div id="bloom.T.malignant_neoplasms_diagnosed_in" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Malignant Neoplasms Diagnosed in Persons in the Bloom Syndrome Registry (1954-2022)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1398/table/bloom.T.malignant_neoplasms_diagnosed_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__bloom.T.malignant_neoplasms_diagnosed_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_1" style="text-align:left;vertical-align:middle;">Malignancy Type/Tissue</th><th id="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" style="text-align:left;vertical-align:middle;">Subtype</th><th id="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" style="text-align:left;vertical-align:middle;">Frequency</th><th id="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4" colspan="3" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Age at Diagnosis (Years)</th></tr><tr><th headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4" id="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Median</th><th headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4" id="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mean</th><th headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4" id="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Range</th></tr></thead><tbody><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">Leukemia</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Acute myeloid</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">22</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">18</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">18</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2-39</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Acute lymphoblastic</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">13</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">15</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">18</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4-40</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Other/biphenotypic/undefined</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">16</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">18</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4-39</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Lymphoma</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">42</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">23</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">23</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4-49</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">Oropharyngeal</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Tongue</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">39</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">40</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">30-48</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Pharynx</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">32</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">34</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">30-45</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Tonsil</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">39.5</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">37.5</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">25-46</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Other</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">31</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">30</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">25-34</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">Upper GI</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Esophageal</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">39</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">37</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">25-48</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gastric</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">27</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">30</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">21-49</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Other</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NA</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NA</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NA</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Colorectal</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">30</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">36</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">35</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">16-49</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">Genitourinary</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cervical</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">22</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">22</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">19-23</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Testicular</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">22</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">19</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10-26</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Other</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">41</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">42</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">33-54</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Breast</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">29</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">32</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">33</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">18-52</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">Skin</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Basal cell</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">18</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">32</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">33</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">18-55</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Squamous cell (uncategorized)</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">8</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">35</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">34</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">25-42</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Other/undefined</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">35</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">34</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">25-42</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Wilms tumor</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">9</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1-11</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Lung</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">36.5</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">36</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">32-40</td></tr><tr><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">All other</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">8</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NA</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NA</td><td headers="hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_1_4 hd_h_bloom.T.malignant_neoplasms_diagnosed_in_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NA</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Adapted from <a class="bk_pop" href="#bloom.REF.sugra_es.2022.1476">Sugrañes et al [2022]</a></p></div></dd><dt></dt><dd><div><p class="no_margin">GI = gastrointestinal; NA = not applicable</p></div></dd></dl></div></div></div><p><b>Myelodysplasia</b> has been diagnosed in 24 persons in the Bloom Syndrome Registry at a median age of 23 years (range: 3-47), and it has progressed to acute myelogenous leukemia in at least seven. In all but three individuals, myelodysplasia was preceded by some form of cancer for which chemotherapy and/or radiotherapy had been administered.</p><p><b>Diabetes mellitus.</b> Abnormalities in insulin release and glucose tolerance have been detected in the eight healthy children (ages nine months to 13 years) and the three healthy young adults with BSyn (ages 22, 28, and 28 years) appropriately studied [<a class="bk_pop" href="#bloom.REF.diaz.2006.111">Diaz et al 2006</a>]. Because of insulin resistance, BSyn-related diabetes mellitus resembles type 2 diabetes but has a much earlier age of onset. Paradoxically, diabetes in persons with BSyn commonly occurs in the setting of low body mass index (BMI), rather than high BMI. Diabetes has been diagnosed in 51 of 294 persons in the Bloom Syndrome Registry (17.3%) at a mean age of 26.2 years (range: 4-48 years). Although most individuals do not have severe complications, a small number of individuals have required insulin or have developed retinopathy.</p><p><b>Chronic obstructive pulmonary disease.</b> Chronic bronchitis and bronchiectasis are common, and pulmonary failure has been the cause of death in six persons.</p><p><b>Hypothyroidism</b> has been recorded in 14 persons in the Bloom Syndrome Registry. Thyroid hormone replacement therapy (levothyroxine) is the commonly reported treatment for underactive thyroid in individuals with BSyn.</p></div><div id="bloom.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No <a class="def" href="/books/n/gene/glossary/def-item/genotype-phenotype-correlations/">genotype-phenotype correlations</a> have been identified.</p></div><div id="bloom.Prevalence"><h3>Prevalence</h3><p>Few individuals with BSyn have been reported in the medical literature since its description half a century ago [<a class="bk_pop" href="#bloom.REF.bloom.1954.754">Bloom 1954</a>], and currently 294 individuals are known to the Bloom Syndrome Registry.</p><p>Although rare in all populations, BSyn is relatively less rare among individuals of <a class="def" href="/books/n/gene/glossary/def-item/ashkenazi-jewish/">Ashkenazi Jewish</a> descent. The predominant <i>BLM</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in individuals of Ashkenazi Jewish descent is <a href="/books/NBK1398/table/bloom.T.blm_pathogenic_variants_referenc/?report=objectonly" target="object" rid-ob="figobbloomTblmpathogenicvariantsreferenc">c.2207_2212delinsTAGATTC</a>, designated blm<sup>Ash</sup>. The approximate <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> frequency of the blm<sup>Ash</sup> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> is 1/157 Ashkenazi Jews dwelling in the United States [<a class="bk_pop" href="#bloom.REF.fares.2008.236">Fares et al 2008</a>] and 1/111 Ashkenazi Jews dwelling in Israel [<a class="bk_pop" href="#bloom.REF.peleg.2002.95">Peleg et al 2002</a>].</p></div></div><div id="bloom.Genetically_Related_Allelic_Disord"><h2 id="_bloom_Genetically_Related_Allelic_Disord_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> pathogenic variants in <i>BLM</i>.</p></div><div id="bloom.Differential_Diagnosis"><h2 id="_bloom_Differential_Diagnosis_">Differential Diagnosis</h2><p>Genetic disorders of interest in the differential diagnosis of Bloom syndrome are listed in <a href="/books/NBK1398/table/bloom.T.genetic_disorders_of_interest_in/?report=objectonly" target="object" rid-ob="figobbloomTgeneticdisordersofinterestin">Table 3</a>.</p><div id="bloom.T.genetic_disorders_of_interest_in" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Genetic Disorders of Interest in the Differential Diagnosis of Bloom Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1398/table/bloom.T.genetic_disorders_of_interest_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__bloom.T.genetic_disorders_of_interest_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene(s) / Genetic Mechanism</th><th id="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_2" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Clinical Features of Disorder</th></tr><tr><th headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4" id="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/BSyn</th><th headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4" id="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from BSyn</th></tr></thead><tbody><tr><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_1 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_2 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_3 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_1 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_2" colspan="5" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;"><b>Disorders w/</b>↑ <b>SCEs & similar clinical findings to BSyn</b></td></tr><tr><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>RMI1</i> <sup>1</sup></td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">RECQ-mediated genome instability 1 (OMIM <a href="https://omim.org/entry/610404" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">610404</a>)</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Small size</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To date, cancer not observed, but reported persons are all relatively young.</div></li><li class="half_rhythm"><div>No abnormal skin findings</div></li></ul>
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</td></tr><tr><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>RMI2</i> <sup>1</sup></td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">RECQ-mediated genome instability 2 (OMIM <a href="https://omim.org/entry/612426" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">612426</a>)</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Small size</div></li><li class="half_rhythm"><div>Café au lait macules</div></li></ul>
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</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To date, cancer not observed, but reported persons are all relatively young.</td></tr><tr><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>TOP3A</i> <sup>1</sup></td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Microcephaly, growth restriction, & ↑ sister-chromatid exchange 2 (OMIM <a href="https://omim.org/entry/618097" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">618097</a>)</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Small size</div></li><li class="half_rhythm"><div>Café au lait macules</div></li><li class="half_rhythm"><div>1 person w/cervical cancer in early adulthood <sup>2</sup></div></li></ul>
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</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>No malar rash</div></li><li class="half_rhythm"><div>Cardiomyopathy <sup>2</sup></div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_1 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_2 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_3 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_1 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_2" colspan="5" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;"><b>Disorders w/similar clinical findings to BSyn, but not assoc w/</b>↑ <b>SCEs</b></td></tr><tr><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Multiple etiologies incl: <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> 11p15 hypomethylation & matUPD7 <sup>3</sup></td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/rss/">Silver-Russell syndrome</a>
|
||
</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 3.</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Growth deficiency</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmalogic abnormalities</td></tr><tr><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>ATM</i>
|
||
</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/ataxia-telangiectas/">Ataxia-telangiectasia</a>
|
||
</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Small stature</div></li><li class="half_rhythm"><div>Evidence of excessive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> instability</div></li><li class="half_rhythm"><div>Telangiectasias</div></li><li class="half_rhythm"><div>Sinopulmonary infection</div></li><li class="half_rhythm"><div>Immunodeficiency</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Progressive cerebellar ataxia from early childhood</div></li><li class="half_rhythm"><div>↑ alpha-fetoprotein levels</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">23 genes incl:<br /><i>FANCA</i><br /><i>FANCC</i><br /><i>FANC</i> <sup>4</sup></td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/fa/">Fanconi anemia</a>
|
||
</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR<br />(AD<br />XL) <sup>5</sup></td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Small stature</div></li><li class="half_rhythm"><div>Evidence of excessive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> instability</div></li><li class="half_rhythm"><div>↑ cancer susceptibility</div></li><li class="half_rhythm"><div>Café au lait macules, hyper- or hypopigmentation</div></li><li class="half_rhythm"><div>↓ fertility</div></li><li class="half_rhythm"><div>Endocrinopathy</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Skeletal malformations</div></li><li class="half_rhythm"><div>Bone marrow failure</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>MRE11</i>
|
||
</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ataxia-telangiectasia-like disorder (OMIM <a href="https://omim.org/entry/604391" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">604391</a>)</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Small stature</div></li><li class="half_rhythm"><div>Evidence of excessive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> instability</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Progressive cerebellar degeneration</div></li><li class="half_rhythm"><div>No telangiectasias or immunodeficiency</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>NBN</i>
|
||
</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/nijmegen/">Nijmegen breakage syndrome</a>
|
||
</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Small stature</div></li><li class="half_rhythm"><div>Evidence of excessive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> instability</div></li><li class="half_rhythm"><div>Immunodeficiency</div></li><li class="half_rhythm"><div>Café au lait macules</div></li><li class="half_rhythm"><div>Predisposition to lymphoid malignancy</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Decline in intellectual performance</div></li><li class="half_rhythm"><div>No telangiectasias</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>WRN</i>
|
||
</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/werner/">Werner syndrome</a>
|
||
</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Small stature</div></li><li class="half_rhythm"><div>Evidence of excessive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> instability</div></li><li class="half_rhythm"><div>↑ incidence of diabetes</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Premature atherosclerosis</div></li><li class="half_rhythm"><div>Prematurely aged appearance</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">RECQL4</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/rts/">Rothmund-Thomson syndrome</a>
|
||
</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Small stature</div></li><li class="half_rhythm"><div>↑ cancer susceptibility</div></li><li class="half_rhythm"><div>Alopecia</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_1_4 hd_h_bloom.T.genetic_disorders_of_interest_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Juvenile cataracts</div></li><li class="half_rhythm"><div>True poikiloderma (not sun-sensitive rash)</div></li><li class="half_rhythm"><div>Premature aging</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">AD = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a>; AR = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a>; BSyn = Bloom syndrome; matUPD7 = maternal <a class="def" href="/books/n/gene/glossary/def-item/uniparental-disomy/">uniparental disomy</a> for <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> 7; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; SCE = sister-chromatid exchange; XL = <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a></p></div></dd><dt>1. </dt><dd><div id="bloom.TF.3.1"><p class="no_margin"><i>RMI1</i>, <i>RMI2</i>, and <i>TOP3A</i> encode proteins that make up the BTRR complex. The <b>B</b>LM protein forms the BTRR complex with topoisomerase 3-alpha (<b>T</b>OP3A) and RecQ-mediated genome instability proteins 1 and 2 (<b>R</b>MI1 and <b>R</b>MI2, respectively). Together, these proteins process double Holliday junctions that arise as a result of homologous-<a class="def" href="/books/n/gene/glossary/def-item/recombination/">recombination</a>-mediated repair of double-stranded DNA breaks during DNA synthesis.</p></div></dd><dt>2. </dt><dd><div id="bloom.TF.3.2"><p class="no_margin">
|
||
<a class="bk_pop" href="#bloom.REF.erdinc.2023.e16775">Erdinc et al [2023]</a>
|
||
</p></div></dd><dt>3. </dt><dd><div id="bloom.TF.3.3"><p class="no_margin">Accurate assessment of Silver-Russell syndrome (SRS) <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> requires identification of the causative genetic mechanism in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>. In most families, a proband with SRS represents a <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> case and has SRS as the result of an apparent <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/epigenetic/">epigenetic</a> or genetic alteration (e.g., loss of paternal <a class="def" href="/books/n/gene/glossary/def-item/methylation/">methylation</a> at the H19/IGF2 <a class="def" href="/books/n/gene/glossary/def-item/imprinting/">imprinting</a> center 1 or maternal <a class="def" href="/books/n/gene/glossary/def-item/uniparental-disomy/">uniparental disomy</a> for <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> 7).</p></div></dd><dt>4. </dt><dd><div id="bloom.TF.3.4"><p class="no_margin">Listed genes represent the most common genetic causes of Fanconi anemia. For other genes associated with this <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>, see <a href="/books/n/gene/fa/">Fanconi Anemia</a>.</p></div></dd><dt>5. </dt><dd><div id="bloom.TF.3.5"><p class="no_margin">Fanconi anemia (FA) can be inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner, an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner (<i>RAD51</i>-related FA), or an <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> manner (<i>FANCB</i>-related FA).</p></div></dd></dl></div></div></div></div><div id="bloom.Management"><h2 id="_bloom_Management_">Management</h2><p>Health supervision recommendations that address diagnosis, treatment, and surveillance for complications in persons with Bloom syndrome (BSyn) have been published [<a class="bk_pop" href="#bloom.REF.cunniff.2018.1872">Cunniff et al 2018</a>].</p><div id="bloom.Evaluations_Following_Initial_Diag"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with BSyn, in addition to the routine medical history, family history, and physical examination, the evaluations summarized in <a href="/books/NBK1398/table/bloom.T.bloom_syndrome_recommended_evalu/?report=objectonly" target="object" rid-ob="figobbloomTbloomsyndromerecommendedevalu">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div id="bloom.T.bloom_syndrome_recommended_evalu" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Bloom Syndrome: Recommended Evaluations Following Initial Diagnosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1398/table/bloom.T.bloom_syndrome_recommended_evalu/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__bloom.T.bloom_syndrome_recommended_evalu_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Feeding/Nutrition/</b>
|
||
<br />
|
||
<b>Gastrointestinal</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consultation w/gastroenterologist &/or feeding specialist</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Eval for gastroesophageal reflux & feeding issues</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Lipid profile</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Beginning at age 10 yrs</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Dermatologic</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Careful history & skin exam for sun-sensitive skin rash, abnormal nevi, & lesions suspicious for basal cell or squamous cell carcinoma</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Immune</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Immunodeficiency screening incl immunoglobulin level, antibody responses to vaccines, & quantitative B & T lymphocytes</div></li><li class="half_rhythm"><div>Referral to immunologist as needed</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In probands w/recurrent, severe, or opportunistic infections</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development/</b>
|
||
<br />
|
||
<b>Neurobehavioral/</b>
|
||
<br />
|
||
<b>Psychosocial</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental, neurobehavioral, & psychosocial assessment</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As needed</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cancer</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Abdominal ultrasound for Wilms tumor</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In probands age ≤8 yrs</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Colonoscopy & fecal immunochemical testing to assess for colorectal cancer</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In probands age ≥10 yrs</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Whole-body MRI for lymphoma</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In probands age ≥12 yrs</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Breast MRI for breast cancer</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In females age ≥18 yrs</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Endocrine</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Men: semen analysis to assess for azoospermia, oligospermia, or asthenospermia</div></li><li class="half_rhythm"><div>Women: assessment for signs of early menopause</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In post-pubertal persons at time of family planning</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Fasting blood glucose & hemoglobin A1c concentration</div></li><li class="half_rhythm"><div>Assessment for polyuria, polydipsia, weight loss</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In probands age ≥10 yrs to evaluate for evidence of diabetes mellitus</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Thyroid function testing: TSH w/reflex to thyroxine</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In probands age ≥10 yrs</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Pulmonary</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for recurrent/chronic pulmonary disease.</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genetic counseling</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>1</sup></td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_evalu_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform affected persons & their families re nature, MOI, & implications of BSyn to facilitate medical & personal decision making</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">BSyn = Bloom syndrome; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; TSH = thyroid-stimulating hormone</p></div></dd></dl></div></div></div></div><div id="bloom.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Treatment recommendations for persons with BSyn have been published [<a class="bk_pop" href="#bloom.REF.cunniff.2018.1872">Cunniff et al 2018</a>]. Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This ideally involves multidisciplinary care by specialists in relevant fields (see <a href="/books/NBK1398/table/bloom.T.bloom_syndrome_treatment_of_mani/?report=objectonly" target="object" rid-ob="figobbloomTbloomsyndrometreatmentofmani">Table 5</a>).</p><div id="bloom.T.bloom_syndrome_treatment_of_mani" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Bloom Syndrome: Treatment of Manifestations</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1398/table/bloom.T.bloom_syndrome_treatment_of_mani/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__bloom.T.bloom_syndrome_treatment_of_mani_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Growth deficiency</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>If GH is prescribed, growth response, serum IGF-1, & IGFBP-3 should be closely monitored.</div></li><li class="half_rhythm"><div>GH should be discontinued if growth velocity does not ↑ w/GH treatment.</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Use of GH has been approached cautiously because of concerns regarding an ↑ risk of developing tumors.</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Feeding/Nutrition/</b>
|
||
<br />
|
||
<b>Gastrointestinal</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Standard treatment for feeding issues incl high-calorie diet</div></li><li class="half_rhythm"><div>Consider consultation w/gastroenterologist or feeding specialist.</div></li><li class="half_rhythm"><div>Reflux precautions & anti-reflux medications as needed</div></li><li class="half_rhythm"><div>Dietary treatment of dyslipidemia according to standard protocols</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Because abnormalities have been identified in lipid profile of persons w/BSyn, caution should be exercised in use of high-fat &/or high-cholesterol diets.</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Dermatologic</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>↓ excessive exposure to sunlight by seeking shade, particularly 10 am to 4 pm.</div></li><li class="half_rhythm"><div>Use sun-protective clothing, incl broad-brimmed hat.</div></li><li class="half_rhythm"><div>UV-blocking sunglasses</div></li><li class="half_rhythm"><div>Use broad-spectrum sunscreen w/SPF 30 2x daily, or every 2-3 hrs when outdoors.</div></li><li class="half_rhythm"><div>Standard treatments for precancerous lesions & skin cancers</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Immune</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Mgmt per immunologist</div></li><li class="half_rhythm"><div>Recurrent infections & defects in humoral immunity: treatment w/immunoglobulins</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development/</b>
|
||
<br />
|
||
<b>Neurobehavioral/</b>
|
||
<br />
|
||
<b>Psychosocial</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Physical, occupational, & speech therapy as needed</div></li><li class="half_rhythm"><div>Educational support as needed</div></li><li class="half_rhythm"><div>Family & teachers are encouraged to relate to persons w/BSyn appropriately for their chronologic age rather than the younger age suggested by their unusually small size.</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cancer</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment of malignancy per oncologist & other relevant specialists:
|
||
<ul><li class="half_rhythm"><div>Modification of standard cancer treatment regimens, usually incl reduction of both dosage & duration</div></li><li class="half_rhythm"><div>Full weight-based dosing may be appropriate for some chemotherapeutic drugs (e.g., steroids, tyrosine kinase inhibitors).</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Due to hypersensitivity to DNA-damaging chemicals & ionizing radiation; persons w/BSyn usually tolerate doses ≤50% of standard chemotherapy dosage, w/no evidence of poorer outcomes.</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">HSCT</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Nonmyeloablative transplantation is likely to be tolerated more than other regimens; required ablative therapy prior to HSCT may require modification of standard protocols because of hypersensitivity to DNA-damaging agents.</div></li><li class="half_rhythm"><div>HSCT has been performed in 3 persons w/leukemia in the Bloom Syndrome Registry. 1 person had >5 yrs disease-free survival before succumbing to another cancer; the other 2 died in immediate post-transplant period.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Endocrine</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Men can consider consulting a fertility specialist. It is unclear if ART is helpful in persons w/oligospermia or other abnormalities.</div></li><li class="half_rhythm"><div>Women: consider oocyte cryopreservation in those w/early menopause; ART may be beneficial if natural conception is not possible.</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">The authors are not aware of any prior use of ART in this population.</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Standard treatment of diabetes mellitus per endocrinologist</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Thyroid hormone replacement therapy is recommended according to standard protocols for treatment of hypothyroidism.</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Pulmonary disease</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cough assist devices, vibration vests, & daily nasal lavage for mucociliary clearance for bronchiectasis</td><td headers="hd_h_bloom.T.bloom_syndrome_treatment_of_mani_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">ART = assisted reproductive technology; BSyn = Bloom syndrome; GH = growth hormone; HSCT = hematopoietic stem cell transplantation; IGF-1 = insulin-like growth factor 1; IGFBP-3 = insulin-like growth factor binding protein 3</p></div></dd></dl></div></div></div></div><div id="bloom.Surveillance"><h3>Surveillance</h3><p>Health supervision recommendations for surveillance in persons with BSyn have been published [<a class="bk_pop" href="#bloom.REF.cunniff.2018.1872">Cunniff et al 2018</a>]. It should be recognized, however, that these recommendations are based on limited data from the Bloom Syndrome Registry and on expert opinion. There are currently no clinical trials or case-control studies that address outcomes in people with BSyn. Because of the unusually high risk for early development of cancer, much of the health supervision effort is directed to early detection and treatment.</p><div id="bloom.T.bloom_syndrome_recommended_surve" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Bloom Syndrome: Recommended Surveillance</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1398/table/bloom.T.bloom_syndrome_recommended_surve/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__bloom.T.bloom_syndrome_recommended_surve_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation</th><th id="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Growth/Feeding/</b>
|
||
<br />
|
||
<b>Nutrition/</b>
|
||
<br />
|
||
<b>Gastrointestinal</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Monitor growth.</div></li><li class="half_rhythm"><div>Assess for feeding issues & gastroesophageal reflux.</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit throughout childhood</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Lipid profile</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually beginning at age 10 yrs</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Skin cancer</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Skin exam w/dermatologist for any suspicious skin lesions</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">On recognition of suspicious lesions & annually thereafter</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Immunology</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for recurrent, severe, or opportunistic infections.</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development/</b>
|
||
<br />
|
||
<b>Neurobehavioral/</b>
|
||
<br />
|
||
<b>Psychosocial</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental, neurobehavioral, & psychosocial assessment</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As needed</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Wilms tumor</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Abdominal ultrasound</div></li><li class="half_rhythm"><div>Screen for signs/symptoms incl hematuria & painless abdominal mass</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 3 mos from time of diagnosis to age 8 yrs</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Leukemia</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Screening & family education on signs/symptoms incl pallor, abnormal bleeding, petechiae, fatigue, unintentional weight loss</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">At every health visit</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Lymphoma</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Screening & family education on signs/symptoms incl enlarged lymph nodes, unexplained fevers, drenching night sweats, fatigue, unintentional weight loss</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Whole-body MRI</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 1-2 yrs beginning at age 12-13 yrs</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Colorectal cancer</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Colonoscopy</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually beginning at age 10-12 yrs</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Fecal immunochemical testing</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 6 mos beginning at age 10-12 yrs</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Breast cancer</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Breast MRI in females</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually beginning at age 18 yrs</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Diabetes mellitus</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Fasting blood glucose & hemoglobin A1c</div></li><li class="half_rhythm"><div>Screening & family education on signs/symptoms of polyuria, polydipsia, weight loss</div></li></ul>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Annually beginning at age 10 yrs</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hypothyroidism</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Serum TSH w/reflex to thyroxine</div></li><li class="half_rhythm"><div>Screening & family education on signs/symptoms incl fatigue, constipation, cold sensitivity, weight gain</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Pulmonary</b>
|
||
</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for recurrent/chronic pulmonary disease.</td><td headers="hd_h_bloom.T.bloom_syndrome_recommended_surve_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">TSH = thyroid-stimulating hormone</p></div></dd></dl></div></div></div></div><div id="bloom.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Sun exposure to the face and other exposed skin, particularly in infancy and early childhood, should be avoided.</p><p>Exposure to ionizing radiation should be minimized. People with BSyn should avoid unnecessary radiographs and CT scans; MRI and ultrasound are preferred imaging modalities when able to be used.</p><p>Chemotherapy can have significant side effects and toxicity (including secondary malignancies). Dose reductions and shortened courses of treatment are generally utilized for individuals with BSyn. Alkylating agents and radiation therapy are considered high risk and are avoided when possible in those with BSyn.</p></div><div id="bloom.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>It is appropriate to evaluate sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> in order to identify as early as possible those who would benefit from avoidance of sun exposure and early surveillance for cancer (see <a href="#bloom.Surveillance">Surveillance</a>).</p><ul><li class="half_rhythm"><div>Molecular genetic testing for the <i>BLM</i> pathogenic variants identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> can be used to evaluate sibs.</div></li><li class="half_rhythm"><div>An unusually low birth weight followed by short stature throughout childhood is typically present in affected sibs; sibs of normal stature are likely unaffected and may not need further testing.</div></li></ul><p>See <a href="#bloom.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to the testing of at-risk relatives for <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> purposes.</p></div><div id="bloom.Pregnancy_Management"><h3>Pregnancy Management</h3><p>Eleven women with BSyn followed in the Bloom Syndrome Registry have become pregnant at least once; seven of them have delivered a total of 11 healthy babies of normal size.</p><p>See <a href="https://www.mothertobaby.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MotherToBaby</a> for more information on medication use during pregnancy.</p></div><div id="bloom.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="bloom.Genetic_Counseling"><h2 id="_bloom_Genetic_Counseling_">Genetic Counseling</h2><p>
|
||
<i>Genetic counseling is the process of providing individuals and families with
|
||
information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
|
||
make informed medical and personal decisions. The following section deals with genetic
|
||
risk assessment and the use of family history and genetic testing to clarify genetic
|
||
status for family members; it is not meant to address all personal, cultural, or
|
||
ethical issues that may arise or to substitute for consultation with a genetics
|
||
professional</i>. —ED.</p><div id="bloom.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Bloom syndrome (BSyn) is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner.</p></div><div id="bloom.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
||
<b>Parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>The parents of an affected individual are presumed to be <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for a <i>BLM</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> to confirm that both parents are <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for a <i>BLM</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> and to allow reliable <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> assessment.</div></li><li class="half_rhythm"><div>If a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is detected in only one parent and parental identity testing has confirmed biological maternity and paternity, it is possible that one of the pathogenic variants identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> occurred as a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> event in the proband or as a <a class="def" href="/books/n/gene/glossary/def-item/postzygotic/">postzygotic</a> <i>de novo</i> event in a mosaic parent [<a class="bk_pop" href="#bloom.REF.j_nsson.2017.519">Jónsson et al 2017</a>]. If the proband appears to have <a class="def" href="/books/n/gene/glossary/def-item/homozygous/">homozygous</a> pathogenic variants (i.e., the same two pathogenic variants), additional possibilities to consider include:</div><ul><li class="half_rhythm"><div>A single- or multiexon <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> that was not detected by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> and that resulted in the artifactual appearance of homozygosity;</div></li><li class="half_rhythm"><div>Uniparental isodisomy for the parental <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> with the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> that resulted in homozygosity for the pathogenic variant in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> [<a class="bk_pop" href="#bloom.REF.woodage.1994.74">Woodage et al 1994</a>].</div></li></ul></li><li class="half_rhythm"><div>Heterozygotes (carriers) are not at risk of developing BSyn. The cancer risk of heterozygotes as a group remains unclear. Some studies have identified a higher rate of <i>BLM</i> heterozygotes among individuals with mesothelioma [<a class="bk_pop" href="#bloom.REF.bononi.2020.33466">Bononi et al 2020</a>], endometrial cancer, and colorectal cancer [<a class="bk_pop" href="#bloom.REF.schayek.2017.365">Schayek et al 2017</a>].</div></li></ul><p>
|
||
<b>Sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>If both parents are known to be <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for a <i>BLM</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, each sib of an affected individual has at conception a 25% chance of inheriting <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic variants and being affected, a 50% chance of being a <a class="def" href="/books/n/gene/glossary/def-item/heterozygote/">heterozygote</a> (<a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>), and a 25% chance of inheriting neither of the <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> pathogenic variants.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are not at risk of developing BSyn. The cancer risk of heterozygotes as a group remains unclear. Some studies have identified a higher rate of <i>BLM</i> heterozygotes among individuals with mesothelioma [<a class="bk_pop" href="#bloom.REF.bononi.2020.33466">Bononi et al 2020</a>], endometrial cancer, and colorectal cancer [<a class="bk_pop" href="#bloom.REF.schayek.2017.365">Schayek et al 2017</a>].</div></li></ul><p>
|
||
<b>Offspring of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>Children born to a female with BSyn are usually <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for a <i>BLM</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>. However, because approximately 1% of individuals of <a class="def" href="/books/n/gene/glossary/def-item/ashkenazi-jewish/">Ashkenazi Jewish</a> descent carry a <i>BLM</i> pathogenic variant, the risk for BSyn in the children of a union between a female with BSyn and a reproductive partner of Ashkenazi Jewish ancestry whose BSyn <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> status has not been determined is 1/200.</div></li><li class="half_rhythm"><div>Children born to a female with BSyn and a reproductive partner who is a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> of a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> have a 50% chance of having BSyn and a 50% chance of being carriers.</div></li><li class="half_rhythm"><div>Males with BSyn tend to be infertile.</div></li></ul><p><b>Other family members.</b> Each sib of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>'s parents is at a 50% risk of being a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> of a <i>BLM</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p></div><div id="bloom.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>BLM</i> pathogenic variants in the family.</p></div><div id="bloom.Population_Screening"><h3>Population Screening</h3><p><b>Individuals of <a class="def" href="/books/n/gene/glossary/def-item/ashkenazi-jewish/">Ashkenazi Jewish</a> ancestry.</b> Because of the relatively increased <a class="def" href="/books/n/gene/glossary/def-item/carrier-rate/">carrier rate</a> of the blm<sup>Ash</sup> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> in the Ashkenazi Jewish population (see <a href="#bloom.Prevalence">Prevalence</a>), individuals of Ashkenazi Jewish ancestry should be aware of their carrier risk, and practitioners should consider screening in this population [<a class="bk_pop" href="#bloom.REF.acog_committee_on_genetics.2017.e41">ACOG Committee on Genetics 2017</a>].</p><p><b>Expanded <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> screening.</b> BSyn is included on most expanded carrier screening panels. The ACMG includes BSyn among those disorders for which carrier screening should be offered to all individuals who are pregnant or planning a pregnancy [<a class="bk_pop" href="#bloom.REF.gregg.2021.1793">Gregg et al 2021</a>].</p></div><div id="bloom.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#bloom.Evaluation_of_Relatives_at_Risk">Evaluation of Relatives at Risk</a> for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.</p><p>
|
||
<b>Family planning</b>
|
||
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.</div></li><li class="half_rhythm"><div>Carrier testing should be offered for the reproductive partners of individuals known to be carriers of BSyn.</div></li></ul></div><div id="bloom.Prenatal_Testing_and_Preimplantati"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p><b>Molecular genetic testing.</b> Once the <i>BLM</i> pathogenic variants have been identified in an affected family member, prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible.</p><p>Note: Ultrasound measurements are not reliable for estimating gestation age if <a class="def" href="/books/n/gene/glossary/def-item/prenatal-diagnosis/">prenatal diagnosis</a> confirms the diagnosis of BSyn in the fetus.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a>. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="bloom.Resources"><h2 id="_bloom_Resources_">Resources</h2><p>
|
||
<i>GeneReviews staff has selected the following disease-specific and/or umbrella
|
||
support organizations and/or registries for the benefit of individuals with this disorder
|
||
and their families. GeneReviews is not responsible for the information provided by other
|
||
organizations. For information on selection criteria, click <a href="/books/n/gene/app4/">here</a>.</i></p>
|
||
<ul><li class="half_rhythm"><div>
|
||
<b>Bloom Syndrome Association</b>
|
||
</div><div>
|
||
<a href="https://www.bloomssyndromeassociation.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.bloomssyndromeassociation.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Bloom Syndrome Registry</b>
|
||
</div><div>Weill Cornell Medicine</div><div>
|
||
<a href="https://pediatrics.weill.cornell.edu/research/bloom-syndrome-registry" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Bloom Syndrome Registry</a>
|
||
</div></li></ul>
|
||
</div><div id="bloom.Molecular_Genetics"><h2 id="_bloom_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div id="bloom.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Bloom Syndrome: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1398/table/bloom.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__bloom.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_bloom.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_bloom.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_bloom.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_bloom.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_bloom.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_bloom.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_bloom.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/641" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>BLM</i>
|
||
</a>
|
||
</td><td headers="hd_b_bloom.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=641" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">15q26<wbr style="display:inline-block"></wbr>.1</a>
|
||
</td><td headers="hd_b_bloom.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/P54132" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RecQ-like DNA helicase BLM</a>
|
||
</td><td headers="hd_b_bloom.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://databases.lovd.nl/shared/genes/BLM" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">BLM database</a>
|
||
<br />
|
||
<a href="http://structure.bmc.lu.se/idbase/BLMbase" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">BLMbase: Mutation registry for Bloom Syndrome</a>
|
||
</td><td headers="hd_b_bloom.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=BLM" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">BLM</a>
|
||
</td><td headers="hd_b_bloom.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=BLM[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">BLM</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="bloom.TFA.1"><p class="no_margin">Data are compiled from the following standard references: <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> from
|
||
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
||
<a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> from
|
||
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
||
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
||
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
||
<a href="/books/n/gene/app1/">here</a>.</p></div></dd></dl></div></div></div><div id="bloom.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Bloom Syndrome (<a href="/omim/210900,604610" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1398/table/bloom.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__bloom.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/210900" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">210900</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">BLOOM SYNDROME; BLM</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/604610" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">604610</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RECQ PROTEIN-LIKE 3; RECQL3</td></tr></tbody></table></div></div><div id="bloom.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>Bloom syndrome (BSyn) is the prototype of the class of human diseases sometimes referred to as the <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> breakage syndromes [<a class="bk_pop" href="#bloom.REF.german.1969.196">German 1969</a>]. These include BSyn, <a href="/books/n/gene/fa/">Fanconi anemia</a>, <a href="/books/n/gene/ataxia-telangiectas/">ataxia-telangiectasia</a>, ataxia-telangiectasia-like disorder (OMIM <a href="https://omim.org/entry/604391" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">604391</a>), <a href="/books/n/gene/nijmegen/">Nijmegen breakage syndrome</a>, and <a href="/books/n/gene/werner/">Werner syndrome</a>. These clinically disparate disorders are caused by pathogenic variants in genes encoding enzymes comprising pathways of DNA replication and repair that are responsible for the maintenance of <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> stability. In all of these disorders, the diagnostic <a class="def" href="/books/n/gene/glossary/def-item/cytogenetic/">cytogenetic</a> abnormalities are accompanied by an increased rate of spontaneous reversion (mutation) to the normal state in somatic cells. This hypermutability explains the cancer predisposition shared by these disorders.</p><p>Molecular and genetic evidence implicates RecQ-like DNA helicase BLM (BLM) in the cellular mechanisms that maintain <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> stability [<a class="bk_pop" href="#bloom.REF.hickson.2001.201">Hickson et al 2001</a>, <a class="bk_pop" href="#bloom.REF.monnat.2010.329">Monnat 2010</a>, <a class="bk_pop" href="#bloom.REF.larsen.2013">Larsen & Hickson 2013</a>, <a class="bk_pop" href="#bloom.REF.suhasini.2013">Suhasini & Brosh 2013</a>, <a class="bk_pop" href="#bloom.REF.cunniff.2017.4">Cunniff et al 2017</a>]. The major consequence of loss of BLM function for a somatic cell is an abnormally high rate of <a class="def" href="/books/n/gene/glossary/def-item/recombination/">recombination</a> and mutation. The pathogenic variants that arise in the cells of a person with BSyn are of several types and affect many regions of the genome. Thus, although the cancer predisposition in BSyn is attributable to the cellular hyper-recombinability and hypermutability, the proportional small size – the constant feature of BSyn – remains unexplained, as do the medical complications of BSyn other than cancer.</p><p><b>Mechanism of disease causation.</b> Loss of function</p><div id="bloom.T.blm_pathogenic_variants_referenc" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p><i>BLM</i> Pathogenic Variants Referenced in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1398/table/bloom.T.blm_pathogenic_variants_referenc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__bloom.T.blm_pathogenic_variants_referenc_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_bloom.T.blm_pathogenic_variants_referenc_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_bloom.T.blm_pathogenic_variants_referenc_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change<br />(Alias <sup>1</sup>)</th><th id="hd_h_bloom.T.blm_pathogenic_variants_referenc_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_bloom.T.blm_pathogenic_variants_referenc_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_bloom.T.blm_pathogenic_variants_referenc_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000057.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000057<wbr style="display:inline-block"></wbr>.2</a>
|
||
<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_000048.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000048<wbr style="display:inline-block"></wbr>.1</a>
|
||
</td><td headers="hd_h_bloom.T.blm_pathogenic_variants_referenc_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.2207_2212delinsTAGATTC <sup>2</sup><br />(2281del6/ins7)</td><td headers="hd_h_bloom.T.blm_pathogenic_variants_referenc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Tyr736LeufsTer5 <sup>2</sup></td><td headers="hd_h_bloom.T.blm_pathogenic_variants_referenc_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in persons of <a class="def" href="/books/n/gene/glossary/def-item/ashkenazi-jewish/">Ashkenazi Jewish</a> descent [<a class="bk_pop" href="#bloom.REF.ellis.1998.1685">Ellis et al 1998</a>]</td></tr><tr><td headers="hd_h_bloom.T.blm_pathogenic_variants_referenc_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.2407dupT<br />(insT2407)</td><td headers="hd_h_bloom.T.blm_pathogenic_variants_referenc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Trp803LeufsTer4</td><td headers="hd_h_bloom.T.blm_pathogenic_variants_referenc_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Second most common variant in persons of <a class="def" href="/books/n/gene/glossary/def-item/ashkenazi-jewish/">Ashkenazi Jewish</a> descent [<a class="bk_pop" href="#bloom.REF.ellis.1998.1685">Ellis et al 1998</a>, <a class="bk_pop" href="#bloom.REF.german.2007.743">German et al 2007</a>]</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>.hgvs.org</a>). See <a href="/books/n/gene/app3/">Quick Reference</a> for an explanation of nomenclature.</p></div></dd><dt>1. </dt><dd><div id="bloom.TF.7.1"><p class="no_margin">Variant designation that does not conform to current naming conventions</p></div></dd><dt>2. </dt><dd><div id="bloom.TF.7.2"><p class="no_margin">Also known as the blm<sup>Ash</sup> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a></p></div></dd></dl></div></div></div></div></div><div id="bloom.Chapter_Notes"><h2 id="_bloom_Chapter_Notes_">Chapter Notes</h2><div id="bloom.Author_Notes"><h3>Author Notes</h3><p>The Bloom Syndrome Registry is a long-term surveillance program in which the clinical courses of persons diagnosed with Bloom syndrome (BSyn) and close members of their families are followed. The Bloom Syndrome Registry includes individuals with confirmed BSyn living in various parts of the world. The registry is the source of much of the data included in this <i>GeneReview</i>.</p><p><b>Bloom Syndrome Registry Contact Information</b><br />Nicole Kucine, MD, MS<br />Weill Cornell Medicine<br />525 E 68th St.<br />Payson-695<br />New York, NY 10021<br />Tel: 212-746-3400<br />Email: <a href="mailto:dev@null" data-email="ude.llenroc.dem@5109kin" class="oemail">ude.llenroc.dem@5109kin</a></p></div><div id="bloom.Acknowledgments"><h3>Acknowledgments</h3><p>The authors would like to acknowledge Dr James L German III (b. January 2, 1926, d. April 21, 2018), who founded the Bloom Syndrome Registry and who dedicated much of his career to the understanding of BSyn and the support of affected persons and their families. They would also like to thank the New York Community Trust and Weill Cornell Medicine's Clinical and Translational Science Center for providing funding.</p></div><div id="bloom.Author_History"><h3>Author History</h3><p>Christopher Cunniff, MD, FACMG (2016-present)<br />Maeve Flanagan, BA; Weill Cornell Medical College (2019-2023)<br />James German, MD, FACMG (hon); Weill Cornell Medical College (2006-2019) <br />Nicole Kucine, MD, MS (2023-present) <br />Katherine Langer, BA (2023-present)<br />Maureen M Sanz, PhD, FACMG; Molloy College (2006-2019)</p></div><div id="bloom.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>12 October 2023 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>14 February 2019 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>7 April 2016 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>28 March 2013 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>24 August 2010 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>22 March 2006 (me) Review posted live</div></li><li class="half_rhythm"><div>10 December 2004 (ms) Original submission</div></li></ul></div></div><div id="bloom.References"><h2 id="_bloom_References_">References</h2><div id="bloom.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="bloom.REF.acog_committee_on_genetics.2017.e41">ACOG Committee on Genetics. 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AP. Mutations in TOP3A cause a Bloom syndrome-like disorder.
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L, Pesso
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K, Omer
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Isr Med Assoc J.
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S, Aziz
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N, Bale
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S, Bick
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D, Das
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J, Grody
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WW, Hegde
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Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
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Genet Med.
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H, Laitman
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Y, Katz
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LH, Pras
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RE, Romain
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DR, Columbano-Green
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LM, Graham
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK1398/?report=reader">PubReader</a></li><li><a href="/books/NBK1398/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK1398" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK1398" style="display:none" title="Cite this Page"><div class="bk_tt">Langer K, Cunniff CM, Kucine N. Bloom Syndrome. 2006 Mar 22 [Updated 2023 Oct 12]. 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class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301575" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Fanconi Anemia.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Fanconi Anemia.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Mehta PA, Ebens C. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301551" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Sickle Cell Disease.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Sickle Cell Disease.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Bender MA, Carlberg K. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301488" ref="ordinalpos=1&linkpos=4&log$=relatedreviews&logdbfrom=pubmed"><span 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xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> INSR-Related Severe Insulin Resistance Syndrome.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> INSR-Related Severe Insulin Resistance Syndrome.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Mesika A, Klar A, Falik Zaccai TC. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=20301572" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See 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href="/portal/utils/pageresolver.fcgi?recordid=67d32b2567c23b31e0209cf8">Bloom Syndrome - GeneReviews®</a><div class="ralinkpop offscreen_noflow">Bloom Syndrome - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=2" href="/portal/utils/pageresolver.fcgi?recordid=67d32b2467c23b31e02092e1">Table B. 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[OMIM Entries for Bloom Syndrome (View All in OMIM)]. - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=3" href="/portal/utils/pageresolver.fcgi?recordid=67d32b0567c23b31e01fbe92">RecName: Full=RecQ-like DNA helicase BLM; AltName: Full=Bloom syndrome protein; ...</a><div class="ralinkpop offscreen_noflow">RecName: Full=RecQ-like DNA helicase BLM; AltName: Full=Bloom syndrome protein; AltName: Full=DNA 3'-5' helicase BLM; AltName: Full=DNA helicase, RecQ-like type 2; Short=RecQ2; AltName: Full=RecQ protein-like 3<div class="brieflinkpopdesc">gi|1705486|sp|P54132.1|BLM_HUMAN</div></div><div class="tertiary">Protein</div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=4" href="/portal/utils/pageresolver.fcgi?recordid=67d32ac384f3725e59a37423">Bloom syndrome</a><div class="ralinkpop offscreen_noflow">Bloom syndrome<div class="brieflinkpopdesc"></div></div><div class="tertiary">MedGen</div></li><li class="ra_qry two_line"><a class="htb" ref="log$=activity&linkpos=5" href="/portal/utils/pageresolver.fcgi?recordid=67d32ac22f30673f7b59c966">C0005859[conceptid] <span class="number">(1)</span></a><div class="tertiary">MedGen</div></li></ul><p class="HTOn">Your browsing activity is empty.</p><p class="HTOff">Activity recording is turned off.</p><p id="turnOn" class="HTOff"><a href="javascript:historyDisplayState('HTOn')">Turn recording back on</a></p><a class="seemore" href="/sites/myncbi/recentactivity">See more...</a></div></div></div>
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<p class="address_footer text-white">National Library of Medicine<br />
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<a href="https://www.google.com/maps/place/8600+Rockville+Pike,+Bethesda,+MD+20894/@38.9959508,-77.101021,17z/data=!3m1!4b1!4m5!3m4!1s0x89b7c95e25765ddb:0x19156f88b27635b8!8m2!3d38.9959508!4d-77.0988323" class="text-white" target="_blank" rel="noopener noreferrer">8600 Rockville Pike<br />
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Bethesda, MD 20894</a></p>
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<p><a href="https://www.nlm.nih.gov/web_policies.html" class="text-white">Web Policies</a><br />
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<a href="https://www.nih.gov/institutes-nih/nih-office-director/office-communications-public-liaison/freedom-information-act-office" class="text-white">FOIA</a><br />
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<a href="https://www.hhs.gov/vulnerability-disclosure-policy/index.html" class="text-white" id="vdp">HHS Vulnerability Disclosure</a></p>
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<div class="col-lg-3 col-12 centered-lg">
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<p><a class="supportLink text-white" href="https://support.nlm.nih.gov/">Help</a><br />
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<a href="https://www.nlm.nih.gov/accessibility.html" class="text-white">Accessibility</a><br />
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<a href="https://www.nlm.nih.gov/careers/careers.html" class="text-white">Careers</a></p>
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<a class="text-white" href="//www.nlm.nih.gov/">NLM</a>
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<li>
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<a class="text-white" href="https://www.nih.gov/">NIH</a>
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<a class="text-white" href="https://www.hhs.gov/">HHS</a>
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<a class="text-white" href="https://www.usa.gov/">USA.gov</a>
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