Retinoblastoma and mosaic 13q deletion: a case report

Background Patients with 13q-syndrome are at risk of retinoblastoma when the RB1 gene, located in the chromosomal band 13q14.2, is deleted. This syndrome is frequently associated with congenital malformations and developmental delay, although these signs could be mild. Mosaic 13q-deletion patients have been previously reported in the literature; their phenotype is variable, and they may not be recognized. Case presentation Retinoblastoma diagnosed in a child with 13q-mosaicism confirmed in blood, oral mucosa, healthy retina and retinoblastoma. A second RB1 hit is present exclusively in the retinoblastoma sample (RB1 c.958C>T p.Arg320Ter). Other detected molecular events in retinoblastoma are 6p12.3pter gain and 6q25.3qter loss. Clinical examination is unremarkable except for clinodactyly of the right fifth finger. Discussion and conclusions We describe a case of mosaic 13q deletion syndrome affected by retinoblastoma. Molecular data obtained from the tumor analysis are similar to previous data available about this malignancy. High clinical suspicion is essential for an adequate diagnosis of mosaic cases.

13q Deletion Syndrome Involving RB1: Characterization of a New Minimal Critical Region for Psychomotor Delay

Retinoblastoma (RB) is an ocular tumor of the pediatric age caused by biallelic inactivation of the RB1 gene (13q14). About 10% of cases are due to gross-sized molecular deletions. The deletions can involve the surrounding genes delineating a contiguous gene syndrome characterized by RB, developmental anomalies, and peculiar facial dysmorphisms. Overlapping deletions previously found by traditional and/or molecular cytogenetic analysis allowed to define some critical regions for intellectual disability (ID) and multiple congenital anomalies, with key candidate genes. In the present study, using array-CGH, we characterized seven new patients with interstitial 13q deletion involving RB1. Among these cases, three patients with medium or large 13q deletions did not present psychomotor delay. This allowed defining a minimal critical region for ID that excludes the previously suggested candidate genes (HTR2A, NUFIP1, PCDH8, and PCDH17). The region contains 36 genes including NBEA, which emerged as the candidate gene associated with developmental delay. In addition, MAB21L1, DCLK1, EXOSC8, and SPART haploinsufficiency might contribute to the observed impaired neurodevelopmental phenotype. In conclusion, this study adds important novelties to the 13q deletion syndrome, although further studies are needed to better characterize the contribution of different genes and to understand how the haploinsufficiency of this region can determine ID.

Deficiency of coagulation factor Vll in a 4 years old child with 13q deletion syndrome: a case report

Background: Factor VII deficiency is rare inherited bleeding disorders, have been identified in the Factor VII gene located on chromosome 13 with very few cases reported. Factor VII deficiency was first described by Alexander et al. in 1951.The disorder has also been known as Alexander's disease. It is the rare inherited bleeding disorders’ with an estimated incidence of 1 case per 3,00,000 to 5,00,000 individuals. Objective and method: We did a case report and literature review for deficiency of coagulation factors VII was found in a 4 years patient who had chromosomal aberration 13q deletion syndrome (46, XX, del 13q32-13q33). This loci involved in synthesis or constitution of factor VII. Results: A review of the gene map of chromosome 13 indicated that Factors VII and X are coded on the long arm of chromosome 13, within the deleted region. Conclusion: Congenital Factor VII deficiency is a rare cause of bleeding disorder, which should be suspected in a bleeding child presenting in infancy when platelets and aPTT are normal with abnormal PT. Congenital Factor VII deficiency association with 46, XX, del (13q32– 13q33) syndrome is very rare disorder and further cases should be reported to know the outcome and the risk of complication in such a cases.

Deficiency of coagulation factor Vll in a 4 years old child with 13q deletion syndrome: a case report

Background: Factor VII deficiency is rare inherited bleeding disorders, have been identified in the Factor VII gene located on chromosome 13 with very few cases reported. Factor VII deficiency was first described by Alexander et al. in 1951.The disorder has also been known as Alexander's disease. It is the rare inherited bleeding disorders’ with an estimated incidence of 1 case per 3,00,000 to 5,00,000 individuals. Objective and method: We did a case report and literature review for deficiency of coagulation factors VII was found in a 4 years patient who had chromosomal aberration 13q deletion syndrome (46, XX, del 13q32-13q33). This loci involved in synthesis or constitution of factor VII. Results: A review of the gene map of chromosome 13 indicated that Factors VII and X are coded on the long arm of chromosome 13, within the deleted region. Conclusion: Congenital Factor VII deficiency is a rare cause of bleeding disorder, which should be suspected in a bleeding child presenting in infancy when platelets and aPTT are normal with abnormal PT. Congenital Factor VII deficiency association with 46, XX, del (13q32– 13q33) syndrome is very rare disorder and further cases should be reported to know the outcome and the risk of complication in such a cases.

Cytogenetic Changes in Multiple Myeloma Timeline: A Tertiary Center's Experience

Introduction Risk stratification in Multiple Myeloma according to cytogenetic abnormalities has been utilized clinically to guide understanding of prognosis. Specific cytogenetics abnormalities such as deletion 17p, t(14,16) and t(4,14) have been associated with more aggressive disease and poor outcome[1]. It has been postulated that genetic aberrations evolve in a temporal pattern in non-hyperploid multiple myeloma such that 13q deletion and t14q32 tend to be early events while chromosome 1 and 17 abnormalities occur as later events [2]. Furthermore, other studies have suggested higher frequencies of high risk cytogenetic abnormalities (such as deletion 17p and gain of 1q) at relapse after upfront autologous stem cell transplant [3]. Our study examined the cytogenetic profile of patients treated at a tertiary health system at the time of diagnosis and at first relapse, irrespective of bone marrow transplant and treatment Methods This is a retrospective study of patients treated at Henry Ford Cancer Institute/Henry Ford Health System. Subjects were adults diagnosed with multiple myeloma with relapse confirmed by a bone marrow biopsy between January 2014 and January 2019. The cytogenetic profile at time of diagnosis and relapse for each patient was reviewed. Exclusion criteria included history or current diagnosis of another malignancy. 145 cases were identified, of which 112 cases were excluded: 19 cases with plasmacytoma but no bone marrow relapse, 32 with other malignancy, 21 with relapse before study period, 5 with relapse after study period, and 35 with bone marrow biopsy or cytogenetics not available for review. As such, we analyzed the remaining 33 cases Results 26 of the 33 cases underwent a bone marrow transplant. A third of the patients (11) developed new mutations, which included 17p deletion (3), 13q deletion (1), chromosome 1 abnormality (1), new trisomies (5), t(11,14) (4), hypoploidy (1), and IgH/CCDN1 changes (1). Conclusion Though cytogenetic evolution in multiple myeloma has been studied, not all patients undergo a bone marrow biopsy and cytogenetic evaluation at relapse, which limits this assessment. Despite our sample size being limited as a majority of the study population did not have cytogenetics recorded at relapse, our study reveals that new mutations can arise in a significant proportion of patients at relapse, some of which are known to be associated with poor prognosis. This can be potentially prognostic, as presence of new high-risk mutations could alter the presumed disease trajectory, and these could also have therapeutic consequences. While further studies with a larger sample size are needed to determine the frequencies of each mutation, our study underscores the importance of dedicated monitoring of cytogenetics at each relapse in multiple myeloma. References Palumbo, A., et al., Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group. J Clin Oncol, 2015. 33(26): p. 2863-9. Jimenez-Zepeda, V.H., E. Braggio, and R. Fonseca, Dissecting karyotypic patterns in non-hyperdiploid multiple myeloma: an overview on the karyotypic evolution. Clin Lymphoma Myeloma Leuk, 2013. 13(5): p. 552-8. Merz, M., et al., Longitudinal fluorescence. Haematologica, 2017. 102(8): p. 1432-1438. Disclosures No relevant conflicts of interest to declare.