BLM keimlinie biallelic pathogene Varianten verursachen Bloom-Syndrom — autosomal-rezessive dis...
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| ID | BMA-BLM-GERMLINE-BLOOM-BROAD |
|---|---|
| Art | Therapeutische Relevanz |
| Status | reviewed 2026-05-18 | pending_clinical_signoff | actionability review required |
| Erkrankungen | DIS-CRC |
| Quellen | SRC-NCCN-PEDIATRIC-SARCOMA |
Fakten zur Handlungsfähigkeit
| Biomarker | BIO-BLM-GERMLINE |
|---|---|
| Variante | BLM-Keimlinien-Biallelik-pathogen (Bloom-Syndrom — breite Krebsanfälligkeit) |
| Erkrankung | DIS-CRC |
| ESCAT-Stufe | IIA |
| Empfohlene Kombinationen | strict UVA/UVB sun protection from infancy (SPF 50+ + protective clothing + UV-blocking eyewear), annual dermatology with comprehensive skin exam (BCC, SCC, melanoma), CBC q3-6mo (leukemia surveillance — AML, ALL, MDS), colonoscopy q1-2y from age 12-15 with polypectomy, EGD q1-2y from age 12-15, breast MRI + mammography annual from age 18-20 (women), low-threshold symptom-directed imaging — atypical cancer presentations at all ages, partner-carrier screening for couples planning children (autosomal-recessive) |
| Kontraindizierte Monotherapie | Wahlhafte ionisierende Strahlenexposition (Diagnose-CT, wenn Alternativen verfügbar, EBRT für solide Tumoren, wenn Alternative verfügbar) — dokumentierte Radiosensitivität bei Bloom-Syndrom |
| Zusammenfassung der Beweise | BLM germline biallelic pathogenic variants cause Bloom syndrome — autosomal-recessive disorder of replication-fork resolution (BLM RecQ helicase loss). Phenotype: severe pre- and postnatal growth restriction, characteristic facial features + sun-sensitive erythematous facial rash (telangiectatic), immunodeficiency, diabetes, and very high lifetime cancer risk with broad spectrum: leukemia (AML, ALL), lymphoma, early colorectal + gastric + skin (BCC, SCC, melanoma) + breast + GU cancers. Median age at first cancer diagnosis ~25 years; many patients develop multiple primary cancers. Confirmed-carrier (biallelic) surveillance protocol (per Bloom Syndrome Registry / Cunniff et al. 2017): strict sun protection from infancy; annual dermatology + comprehensive skin exam; complete blood count q3-6mo (leukemia surveillance); colonoscopy q1-2y starting age 12-15 with polypectomy; EGD q1-2y from age 12-15; breast MRI + mammography annual from age 18-20 in women; symptom-directed evaluation with low threshold (cancers present atypically and at all ages). Avoid ionizing radiation when possible —... |
Anmerkungen
STUB — Wave A+B germline expansion. Linked Indication: none (no Bloom- specific Indication exists yet). Two-Clinical-Co-Lead signoff queued. Critical: only biallelic carriers face the Bloom-phenotype cancer risk. Heterozygous BLM (including BLM-Ash Ashkenazi founder) — at most modest elevation; not currently a routine surveillance indication. Cytotoxic chemotherapy dose-reductions may be required due to underlying genomic instability and bone-marrow fragility — consult with center experienced in Bloom syndrome before any oncologic treatment.
Verwendet von
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