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Aboul Hosn O, Abou Chaar J, Abi Zeid Daou C, Ibrahim A, Al Barazi R. A Complex Case of Diffused Malignant Extra-Renal Rhabdoid Tumor in a Newborn. EAR, NOSE & THROAT JOURNAL 2025:1455613251325041. [PMID: 40107999 DOI: 10.1177/01455613251325041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/22/2025] Open
Abstract
Malignant rhabdoid tumor (MRT), first described by Beckwith and Palmer in 1978 as a variant of Wilms' tumor, is an aggressive neoplasm with early onset and poor prognosis. Malignant extra-renal rhabdoid tumors (MERTs) can arise in various locations and often present at birth as a disseminated disease without an identifiable primary site, posing significant diagnostic and therapeutic challenges. This case highlights the complexity of diagnosing an 11-day-old preterm infant with multiple enlarging masses, including a hypervascular forehead lesion, parotid mass, and soft tissue masses in the leg and hip. Initial imaging, pathology, and immunohistochemistry findings were inconclusive, necessitating advanced molecular studies, which ultimately confirmed MRTs through the loss of SMARCB1 expression. However, the diagnosis was delayed due to overlapping differential considerations, including fibrosarcoma and other sarcomas. Despite extensive multidisciplinary efforts and tailored treatments, the tumors progressed aggressively, emphasizing the challenges in diagnosing and managing such rare conditions. Given their complexity, MERTs require a comprehensive diagnostic approach combining clinical evaluation, histopathological analysis, and molecular studies, with a high level of clinical suspicion essential for timely treatment.
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Affiliation(s)
- Omar Aboul Hosn
- Department of Otolaryngology-Head and Neck Surgery, American University of Beirut Medical Center, Lebanon
| | - Jonathan Abou Chaar
- Department of Otolaryngology-Head and Neck Surgery, American University of Beirut Medical Center, Lebanon
| | - Christophe Abi Zeid Daou
- Department of Otolaryngology-Head and Neck Surgery, American University of Beirut Medical Center, Lebanon
| | - Amir Ibrahim
- Division of Plastic and Reconstructive Surgery, American University of Beirut Medical Center, Lebanon
| | - Randa Al Barazi
- Department of Otolaryngology-Head and Neck Surgery, American University of Beirut Medical Center, Lebanon
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2
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Mathews I, Munisamy M, Govindarajan KK, Srinivas BH, Badhe BA. Papillomatous plaque in an infant. Pediatr Dermatol 2023; 40:946-948. [PMID: 36905165 DOI: 10.1111/pde.15289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Accepted: 02/19/2023] [Indexed: 03/12/2023]
Affiliation(s)
- Irene Mathews
- Department of Dermatology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Malathi Munisamy
- Department of Dermatology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Krishana Kumar Govindarajan
- Department of Paediatric Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Bheemanathi H Srinivas
- Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Bhawna A Badhe
- Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
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3
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Frühwald MC, Nemes K, Boztug H, Cornips MCA, Evans DG, Farah R, Glentis S, Jorgensen M, Katsibardi K, Hirsch S, Jahnukainen K, Kventsel I, Kerl K, Kratz CP, Pajtler KW, Kordes U, Ridola V, Stutz E, Bourdeaut F. Current recommendations for clinical surveillance and genetic testing in rhabdoid tumor predisposition: a report from the SIOPE Host Genome Working Group. Fam Cancer 2021; 20:305-316. [PMID: 33532948 PMCID: PMC8484234 DOI: 10.1007/s10689-021-00229-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Accepted: 01/06/2021] [Indexed: 12/28/2022]
Abstract
The rhabdoid tumor (RT) predisposition syndromes 1 and 2 (RTPS1 and 2) are rare genetic conditions rendering young children vulnerable to an increased risk of RT, malignant neoplasms affecting the kidney, miscellaneous soft-part tissues, the liver and the central nervous system (Atypical Teratoid Rhabdoid Tumors, ATRT). Both, RTPS1&2 are due to pathogenic variants (PV) in genes encoding constituents of the BAF chromatin remodeling complex, i.e. SMARCB1 (RTPS1) and SMARCA4 (RTPS2). In contrast to other genetic disorders related to PVs in SMARCB1 and SMARCA4 such as Coffin-Siris Syndrome, RTPS1&2 are characterized by a predominance of truncating PVs, terminating transcription thus explaining a specific cancer risk. The penetrance of RTPS1 early in life is high and associated with a poor survival. However, few unaffected carriers may be encountered. Beyond RT, the tumor spectrum may be larger than initially suspected, and cancer surveillance offered to unaffected carriers (siblings or parents) and long-term survivors of RT is still a matter of discussion. RTPS2 exposes female carriers to an ill-defined risk of small cell carcinoma of the ovaries, hypercalcemic type (SCCOHT), which may appear in prepubertal females. RT surveillance protocols for these rare families have not been established. To address unresolved issues in the care of individuals with RTPS and to propose appropriate surveillance guidelines in childhood, the SIOPe Host Genome working group invited pediatric oncologists and geneticists to contribute to an expert meeting. The current manuscript summarizes conclusions of the panel discussion, including consented statements as well as non-evidence-based proposals for validation in the future.
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Affiliation(s)
- M C Frühwald
- Paediatric and Adolescent Medicine, Swabian Children's Cancer Center, University Medical Center Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany.
| | - K Nemes
- Paediatric and Adolescent Medicine, Swabian Children's Cancer Center, University Medical Center Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany
| | - H Boztug
- St. Anna Children's Hospital and Children's Cancer Research Institute, Department of Pediatrics, Medical University of Vienna, Vienna, Austria
| | - M C A Cornips
- Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
| | - D G Evans
- Manchester Centre for Genomic Medicine, Division of Evolution and Genomic Sciences, MAHSC, St Mary's Hospital, Manchester University Hospitals NHS Foundation Trust, University of Manchester, Manchester, UK
| | - R Farah
- Department of Pediatrics, Division of Hematology/Oncology, LAU Medical Center-Rizk Hospital, Ashrafieh, Beirut, Lebanon
| | - S Glentis
- Pediatric Hematology-Oncology Unit, First Department of Pediatrics, National and Kapodistrian University of Athens, "Aghia Sofia" Children's Hospital, Athens, Greece
| | - M Jorgensen
- Great Ormond Street Hospital for Children, NHS Foundation Trust, London, WC1N 3JH, UK
| | - K Katsibardi
- Pediatric Hematology-Oncology Unit, First Department of Pediatrics, National and Kapodistrian University of Athens, "Aghia Sofia" Children's Hospital, Athens, Greece
| | - S Hirsch
- Institute of Human Genetics, Heidelberg University Hospital, Heidelberg, Germany.,Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
| | - K Jahnukainen
- Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - I Kventsel
- Department of Pediatric Hematology-Oncology, The Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center, 52621, Tel-Hashomer, Israel
| | - K Kerl
- Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany
| | - C P Kratz
- Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
| | - K W Pajtler
- Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.,Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.,Department of Pediatric Oncology, Hematology, and Immunology, University Hospital Heidelberg, Heidelberg, Germany
| | - U Kordes
- Department of Pediatric Hematology and Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany
| | - V Ridola
- Department of Pediatric Oncology and Haematology, Mitera Children's Hospital, Athens, Greece
| | - E Stutz
- Department of Oncology, University Children's Hospital, Zurich, Switzerland
| | - F Bourdeaut
- Institut Curie, SIREDO Pediatric Cancer Center, INSERM U830, Laboratory of Translational Research in Pediatric Oncology, Paris Sciences Lettres Research University, Paris, France.
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Cohen S, Gurvitz MZ, Beauséjour-Ladouceur V, Lawler PR, Therrien J, Marelli AJ. Cancer Risk in Congenital Heart Disease-What Is the Evidence? Can J Cardiol 2019; 35:1750-1761. [PMID: 31813507 DOI: 10.1016/j.cjca.2019.09.023] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 09/13/2019] [Accepted: 09/17/2019] [Indexed: 12/18/2022] Open
Abstract
As life expectancy in patients with congenital heart disease (CHD) has improved, the risk for developing noncardiac morbidities is increasing in adult patients with CHD (ACHD). Among these noncardiac complications, malignancies significantly contribute to the disease burden of ACHD patients. Epidemiologic studies of cancer risk in CHD patients are challenging because they require large numbers of patients, extended follow-up, detailed and validated clinical data, and appropriate reference populations. However, several observational studies suggest that cancer risks are significantly elevated in patients with CHD compared with the general population. CHD and cancer share genetic and environmental risk factors. An association with exposure to low-dose ionizing radiation secondary to medical therapeutic or diagnostic procedures has been reported. Patients with Down syndrome, as well as, to a lesser extent, deletion of 22q11.2 and renin-angiotensin system pathologies, may manifest both CHD and a predisposition to cancer. Such observations suggest that carcinogenesis and CHD may share a common basis in some cases. Finally, specific conditions, such as Fontan circulation and cyanotic CHD, may lead to multisystem consequences and subsequently to cancer. Nonetheless, there is currently no clear consensus regarding appropriate screening for cancer and surveillance modalities in CHD patients. Physicians caring for patients with CHD should be aware of this potential predisposition and meet screening recommendations for the general population fastidiously. An interdisciplinary and global approach is required to bridge the knowledge gap in this field.
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Affiliation(s)
- Sarah Cohen
- Congenital Heart Diseases Department, Complex Congenital Heart Diseases M3C Network, Hospital Marie Lannelongue, Paris-Sud University, Paris-Saclay University, Le Plessis-Robinson, France
| | - Michelle Z Gurvitz
- Department of Cardiology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA
| | | | - Patrick R Lawler
- Peter Munk Cardiac Centre, Toronto General Hospital, Toronto, Ontario, Canada; Heart and Stroke/Richard Lewar Centre for Excellence, University of Toronto, Toronto, Ontario, Canada; Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada
| | - Judith Therrien
- McGill Adult Unit for Congenital Heart Disease Excellence, Montréal, Québec, Canada
| | - Ariane J Marelli
- McGill Adult Unit for Congenital Heart Disease Excellence, Montréal, Québec, Canada.
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Nemes K, Clément N, Kachanov D, Bens S, Hasselblatt M, Timmermann B, Schneppenheim R, Gerss J, Siebert R, Furtwängler R, Bourdeaut F, Frühwald MC. The extraordinary challenge of treating patients with congenital rhabdoid tumors-a collaborative European effort. Pediatr Blood Cancer 2018; 65:e26999. [PMID: 29418059 DOI: 10.1002/pbc.26999] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Revised: 12/21/2017] [Accepted: 01/02/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND Congenital rhabdoid tumors are rare and highly aggressive malignancies. In general, patients are considered to be incurable and are often treated using an exclusive, primarily palliative approach. METHODS A prospective and retrospective collection of 42 patients from the European Rhabdoid Registry (EU-RHAB), France and Moscow (2006-2016) diagnosed within the first 28 days of life was evaluated. Genetic and clinical reference evaluation included SMARCB1 and/or SMARCA4 (fluorescence-in-situ-hybridization, multiplex ligation-dependent probe amplification, and sequencing) mutation analysis and immunohistochemistry. Forty-eight percent (20/42) of patients were treated according to the EU-RHAB therapy, 7% (3/42) according to the pilot approach Rhabdoid 2007, 33% (14/42) with individual schedules, and 12% (5/42) received no chemotherapy at all. RESULTS Forty point five percent (17/42) of patients presented with extracranial rhabdoid tumors, 33.5% (14/42) with rhabdoid tumors of the central nervous system (atypical teratoid/rhabdoid tumor), and the remainder 26% (11/42) demonstrated synchronous tumors. Metastases at diagnosis were present in 52% (22/42) of patients. A germline mutation was detected in 66% (25/38) and was associated with a poor prognosis (4.2 ± 4.1% vs. 48 ± 16.4%, P < 0.00005). A gross total resection (GTR) was realized in 17%. A GTR (42.9 ± 18.7% vs. 4.9 ± 4.3%, P = 0.04), therapy according to a standardized approach (20.9 ± 8.7% vs. 7.1 ± 6.9 %, P = 0.0018), and a complete remission (CR) (23.6 ± 9.8% vs. 1.3 ± 3.6%, P = 0.04) were significant prognostic factors. CONCLUSIONS The management of patients with congenital rhabdoid tumors requires a major multidisciplinary effort. In many instances, cure is not possible and a palliative approach is warranted. Our data indicate a positive impact of standardized therapeutic approaches on survival, making a tailored approach toward affected patients and their families mandatory.
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Affiliation(s)
- Karolina Nemes
- Swabian Children's Cancer Center, Children's Hospital, Klinikum Augsburg, Augsburg, Germany
| | - Nathalie Clément
- Pediatric care and research Center, Institute Curie, PSL Research University, Paris, France
| | - Denis Kachanov
- National Scientific and Practical Center of Pediatric Hematology, Oncology, and Immunology named after Dmitry Rogachev, Moscow, Russian Federation
| | - Susanne Bens
- Institute of Human Genetics, University of Ulm & University Hospital of Ulm, Ulm, Germany
| | - Martin Hasselblatt
- Institute of Neuropathology, University Hospital Muenster, Muenster, Germany
| | - Beate Timmermann
- Clinic for Particle Therapy, West German Cancer Center (WTZ), University Hospital Essen, Essen, Germany
| | - Reinhard Schneppenheim
- Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Joachim Gerss
- Institute of Biostatistics and Clinical Research, University of Münster, Muenster, Germany
| | - Reiner Siebert
- Institute of Human Genetics, University of Ulm & University Hospital of Ulm, Ulm, Germany
| | - Rhoikos Furtwängler
- Department of Pediatric Oncology and Hematology, Saarland University of Hospital Saarland, Saarland, Germany
| | - Franck Bourdeaut
- Pediatric care and research Center, Institute Curie, PSL Research University, Paris, France
| | - Michael Christoph Frühwald
- Swabian Children's Cancer Center, Children's Hospital, Klinikum Augsburg, Augsburg, Germany.,Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, University of Muenster, Muenster, Germany
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6
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Lambert MP, Arulselvan A, Schott A, Markham SJ, Crowley TB, Zackai EH, McDonald-McGinn DM. The 22q11.2 deletion syndrome: Cancer predisposition, platelet abnormalities and cytopenias. Am J Med Genet A 2017; 176:2121-2127. [PMID: 28940864 DOI: 10.1002/ajmg.a.38474] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2017] [Revised: 08/08/2017] [Accepted: 08/21/2017] [Indexed: 01/10/2023]
Abstract
The 22q11.2 deletion syndrome (DS) is associated with variable phenotypic expression as findings range from severely affected individuals with the classical triad of DiGeorge and velocardiofacial syndromes, including congenital heart disease, immunodeficiency, hypocalcemia, and palatal abnormalities, to subtly affected adults who only come to attention following the diagnosis of a more severely affected child. The multiple manifestations can affect all organ systems, including the hematologic system resulting in baseline lower platelet counts for individuals with 22q11.2DS and increased platelet size. In addition, there may be an associated increased risk of bleeding. Individuals with 22q11.2DS are also at increased risk of autoimmune cytopenias that can complicate the evaluation or management of other manifestations. Finally, there may be an increased risk of malignancy, although the mechanism for this risk is not fully understood. This review summarizes the currently available data on hematologic/oncologic manifestations of 22q11.2DS and reports on our findings within a large cohort of individuals with the deletion.
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Affiliation(s)
- Michele P Lambert
- Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.,Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
| | - Abinaya Arulselvan
- Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Amanda Schott
- Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.,Arcadia University, Glenside, Pennsylvania
| | - Stephen J Markham
- Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Terrance B Crowley
- Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Elaine H Zackai
- Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.,Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
| | - Donna M McDonald-McGinn
- Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.,Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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7
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Bartelheim K, Sumerauer D, Behrends U, Kodetova D, Kucera F, Leuschner I, Neumayer P, Oyen F, Rübe C, Siebert R, Schneppenheim R, Seeringer A, Vasovcak P, Frühwald MC. Clinical and genetic features of rhabdoid tumors of the heart registered with the European Rhabdoid Registry (EU-RHAB). Cancer Genet 2014; 207:379-83. [PMID: 24972932 DOI: 10.1016/j.cancergen.2014.04.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 04/09/2014] [Accepted: 04/15/2014] [Indexed: 10/25/2022]
Abstract
Rhabdoid tumors are rare but highly aggressive malignancies of infancy and early childhood with a generally unfavorable prognosis. Despite a wide variety of anatomic locations rhabdoid tumors share mutational inactivation of the SWI/SNF (SWItch/Sucrose NonFermentable) core component gene SMARCB1 (also known as INI1, hSNF5 or BAF47) in chromosome 22. As this inactivation usually results in loss of SMARCB1 expression, detectable by an antibody against the SMARCB1 protein, the accurate diagnosis of a rhabdoid tumor may be more distinctly and frequently made. Several reports on rhabdoid tumors presenting in various anatomic sites outside the kidneys and CNS are on record. We report two cases of rhabdoid tumors originating in the heart (cardiac tissue), which were entered into the European Rhabdoid Registry (EU-RHAB). The first case presented with intracardial and -cranial lesions as well as malignant ascites, while the second patient demonstrated an isolated cardiac tumor. This induced a different therapeutic approach and subsequently different clinical course (death 7 weeks after diagnosis in patient 1). Patient 2 presented with a bifocal intracardial tumor without metastases and remains in complete remission for 46 months since diagnosis following multimodal therapy. The second case demonstrates that even in a potentially futile clinical situation early and accurate diagnosis followed by prompt and intensive multimodal therapy may offer prolonged survival, potential cure and improved quality of life.
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Affiliation(s)
- Kerstin Bartelheim
- Children's Hospital Augsburg, Swabian Children's Cancer Center, Augsburg, Germany
| | - David Sumerauer
- Department of Pediatric Hematology and Oncology, University Hospital Motol, Charles University, 2nd Medical School, Prague, Czech Republic
| | - Uta Behrends
- Department of Pediatric Hematology and Oncology, Childrens' Hospital Schwabing, University of Technology, Munich, Germany
| | - Daniela Kodetova
- Department of Pathology and Molecular Medicine, University Hospital Motol, Charles University, 2nd Medical School, Prague, Czech Republic
| | - Filip Kucera
- Kardiocentrum and Cardiovascular Research Centre, University Hospital Motol, Prague, Czech Republic
| | - Ivo Leuschner
- Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University Kiel, Germany
| | - Petra Neumayer
- Children's Hospital Augsburg, Swabian Children's Cancer Center, Augsburg, Germany
| | - Florian Oyen
- Department of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Germany
| | - Christian Rübe
- Department of Radiology, University of the Saarland, Homburg Saar, Germany
| | - Reiner Siebert
- Institute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Reinhard Schneppenheim
- Department of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Germany
| | - Angela Seeringer
- Children's Hospital Augsburg, Swabian Children's Cancer Center, Augsburg, Germany
| | - Peter Vasovcak
- Department of Biology and Medical Genetics, University Hospital Motol, Charles University, 2nd Medical School, Prague, Czech Republic
| | - Michael C Frühwald
- Children's Hospital Augsburg, Swabian Children's Cancer Center, Augsburg, Germany; Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, Germany.
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Mikhail FM, Burnside RD, Rush B, Ibrahim J, Godshalk R, Rutledge SL, Robin NH, Descartes MD, Carroll AJ. The recurrent distal 22q11.2 microdeletions are often de novo and do not represent a single clinical entity: a proposed categorization system. Genet Med 2013; 16:92-100. [PMID: 23765049 DOI: 10.1038/gim.2013.79] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2012] [Accepted: 04/25/2013] [Indexed: 01/06/2023] Open
Abstract
PURPOSE The five segmental duplications (LCR22-D to -H) at the distal region of chromosome 22 band q11.2 in the region immediately distal to the DiGeorge/velocardiofacial syndrome deleted region have been implicated in the recurrent distal 22q11.2 microdeletions. To date, the distal 22q11.2 microdeletions have been grouped together as a single clinical entity despite the fact that these deletions are variable in size and position depending on the mediating LCR22s. METHODS Here, we report 13 new unrelated patients with variable size deletions in the distal 22q11.2 region as shown by cytogenomic array analyses. We compare our patients' clinical features with those of previously reported cases to better dissect the phenotypic correlations based on the deletion size and position. RESULTS Six patients had the 1.1-Mb deletion flanked by LCR22-D and -E, and presented clinically with a phenotype consistent with previously reported cases with distal 22q11.2 microdeletions. Three patients had the 1.8-Mb deletion flanked by LCR22-D and -F, and presented with a similar phenotype. Four patients had the 700-kb deletion flanked by LCR22-E and -F, and presented with a milder phenotype that lacked growth restriction and cardiovascular defects. CONCLUSION We suggest that the recurrent distal 22q11.2 microdeletions do not represent a single clinical entity, and propose categorizing these deletions into three types according to their genomic position. All three deletion types are thought to be pathogenic and are most often de novo. They all share some presenting features but also have their unique features and risks.
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Affiliation(s)
- Fady M Mikhail
- Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Rachel D Burnside
- Laboratory Corporation of America, Research Triangle Park, North Carolina, USA
| | - Brooke Rush
- Laboratory Corporation of America, Research Triangle Park, North Carolina, USA
| | - Jennifer Ibrahim
- Department of Pediatrics, Division of Genetics, St. Joseph's Children's Hospital, Paterson, New Jersey, USA
| | - Robin Godshalk
- Department of Pediatrics, Division of Genetics, St. Joseph's Children's Hospital, Paterson, New Jersey, USA
| | - S Lane Rutledge
- Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Nathaniel H Robin
- Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Maria D Descartes
- Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Andrew J Carroll
- Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA
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