Diagnosis of Bloom Syndrome in a Patient with Short Stature, Recurrence of Malignant Lymphoma, and Consanguineous Origin

Abstract

Bloom syndrome is an autosomal recessive disorder characterized by prenatal and postnatal growth deficiency, photosensitive skin changes, immune deficiency, insulin resistance, and a greatly increased risk of early-onset cancer and development of multiple malignancies. Loss-of-function variants of the BLM gene, which codes for a RecQ helicase, cause Bloom syndrome. We report a consanguineous family, with 2 siblings showing clinical signs of suspected chromosome breakage disorder. One of them developed recurrent malignant lymphoma during lifetime. We performed next-generation sequencing analysis, focusing on cancer predisposition syndromes. We identified a homozygous pathogenic nonsense variant c.1642C>T (p.Gln548*) in the BLM gene in the proband, associated with Bloom syndrome. Sanger sequencing validated the presence of a homozygous pathogenic variant in the proband and also in the brother with short stature. In this article, we will focus on the clinical presentation of the syndrome in this particular family as well as the characteristics of malignancies found in the proband.

Primary Colonic Diffuse Large B-Cell Lymphoma in Bloom Syndrome

“…5,6 Case reports of lymphomatous neoplasms have been described in the literature and via the Bloom syndrome registry. 3,4,7–9 However, this case report of a primary colonic diffuse large B-cell lymphoma in a patient with Bloom syndrome is the first described, to our knowledge. Although the etiology of lymphoma development at the site of ileocolonic anastomosis in our patient is unclear, she did have an abscess at the anastomosis shortly after the subcolectomy.…”

Bloom Syndrome Complicated by Low-Grade Lymphoma and Non-small Cell Lung Cancer: A Case Report

“…While there are no established guidelines on treating B-cell lymphoma in BS patients, several case reports have detailed the treatment of this condition in these patients with varying success [ 11 , 12 , 13 ]. The treatment regimens used include a rituximab-based chemotherapy protocol [ 11 ], high-dose methotrexate and high-dose cyclophosphamide [ 12 ], and R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone) [ 13 ]. Further research is needed to delineate evidence-based guidelines for managing this common type of cancer in BS patients.…”

A unique case of Bloom syndrome with a combination of genetic hits: A lesson from trio‑based exome sequencing: A case report

“…The recurrent variant c.1642c>T is enriched in the eastern europe population of the Slavic origin, in which 0.2-0.6% individuals are its carriers. only a few patients with Bloom syndrome carrying homozygous c.1642c>T variant are described in a scientific literature, probably due to the incomplete phenotypic manifestation lacking the presence of a typical uV exposure-induced facial erythema (27,28). it raises the hypothesis of the underdiagnosis of Bloom syndrome at the clinical and molecular level in this population.…”