Idiopathic splenomegaly in childhood and the spectrum of RAS-associated lymphoproliferative disease: a case report
Abstract Background KRAS (KRAS proto-oncogene, GTPase; OMIM: 190,070) encodes one of three small guanosine triphosphatase proteins belonging to the RAS family. This group of proteins is responsible for cell proliferation, differentiation and inhibition of apoptosis. Gain-of-function variants in KRAS...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | BMC Pediatrics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12887-021-02508-3 |
| _version_ | 1818561587747749888 |
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| author | Geraldine Blanchard-Rohner Robert J. Ragotte Anne K. Junker Mehul Sharma Kate L. Del Bel Henry Y. Lu Stephanie Erdle Alanna Chomyn Harinder Gill Lori B. Tucker Richard A. Schreiber Jacob Rozmus Catherine M. Biggs Kyla J. Hildebrand John Wu Sylvia Stockler-Ipsiroglu Stuart E. Turvey |
| author_facet | Geraldine Blanchard-Rohner Robert J. Ragotte Anne K. Junker Mehul Sharma Kate L. Del Bel Henry Y. Lu Stephanie Erdle Alanna Chomyn Harinder Gill Lori B. Tucker Richard A. Schreiber Jacob Rozmus Catherine M. Biggs Kyla J. Hildebrand John Wu Sylvia Stockler-Ipsiroglu Stuart E. Turvey |
| author_sort | Geraldine Blanchard-Rohner |
| collection | DOAJ |
| description | Abstract Background KRAS (KRAS proto-oncogene, GTPase; OMIM: 190,070) encodes one of three small guanosine triphosphatase proteins belonging to the RAS family. This group of proteins is responsible for cell proliferation, differentiation and inhibition of apoptosis. Gain-of-function variants in KRAS are commonly found in human cancers. Non-malignant somatic KRAS variants underlie a subset of RAS-associated autoimmune leukoproliferative disorders (RALD). RALD is characterized by splenomegaly, persistent monocytosis, hypergammaglobulinemia and cytopenia, but can also include autoimmune features and lymphadenopathy. In this report, we describe a non-malignant somatic variant in KRAS with prominent clinical features of massive splenomegaly, thrombocytopenia and lymphopenia. Case presentation A now-11-year-old girl presented in early childhood with easy bruising and bleeding, but had an otherwise unremarkable medical history. After consulting for the first time at 5 years of age, she was discovered to have massive splenomegaly. Clinical follow-up revealed thrombocytopenia, lymphopenia and increased polyclonal immunoglobulins and C-reactive protein. The patient had an unremarkable bone marrow biopsy, flow cytometry showed no indication of expanded double negative T-cells, while malignancy and storage disorders were also excluded. When the patient was 8 years old, whole exome sequencing performed on DNA derived from whole blood revealed a heterozygous gain-of-function variant in KRAS (NM_004985.5:c.37G > T; (p.G13C)). The variant was absent from DNA derived from a buccal swab and was thus determined to be somatic. Conclusions This case of idiopathic splenomegaly in childhood due to a somatic variant in KRAS expands our understanding of the clinical spectrum of RAS-associated autoimmune leukoproliferative disorder and emphasizes the value of securing a molecular diagnosis in children with unusual early-onset presentations with a suspected monogenic origin. |
| first_indexed | 2024-12-14T00:52:48Z |
| format | Article |
| id | doaj.art-f24191a4b05b48ae9100760d3fafe294 |
| institution | Directory Open Access Journal |
| issn | 1471-2431 |
| language | English |
| last_indexed | 2024-12-14T00:52:48Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pediatrics |
| spelling | doaj.art-f24191a4b05b48ae9100760d3fafe2942022-12-21T23:23:45ZengBMCBMC Pediatrics1471-24312021-01-012111410.1186/s12887-021-02508-3Idiopathic splenomegaly in childhood and the spectrum of RAS-associated lymphoproliferative disease: a case reportGeraldine Blanchard-Rohner0Robert J. Ragotte1Anne K. Junker2Mehul Sharma3Kate L. Del Bel4Henry Y. Lu5Stephanie Erdle6Alanna Chomyn7Harinder Gill8Lori B. Tucker9Richard A. Schreiber10Jacob Rozmus11Catherine M. Biggs12Kyla J. Hildebrand13John Wu14Sylvia Stockler-Ipsiroglu15Stuart E. Turvey16Department of Pediatrics, British Columbia Children’s Hospital, The University of British ColumbiaJenner Institute, Nuffield Department of Medicine, University of OxfordDepartment of Pediatrics, British Columbia Children’s Hospital, The University of British ColumbiaDepartment of Pediatrics, British Columbia Children’s Hospital, The University of British ColumbiaDepartment of Pediatrics, British Columbia Children’s Hospital, The University of British ColumbiaDepartment of Pediatrics, British Columbia Children’s Hospital, The University of British ColumbiaDepartment of Pediatrics, British Columbia Children’s Hospital, The University of British ColumbiaDepartment of Pediatrics, British Columbia Children’s Hospital, The University of British ColumbiaDepartment of Medical Genetics, The University of British ColumbiaDepartment of Pediatrics, British Columbia Children’s Hospital, The University of British ColumbiaDepartment of Pediatrics, British Columbia Children’s Hospital, The University of British ColumbiaDepartment of Pediatrics, British Columbia Children’s Hospital, The University of British ColumbiaDepartment of Pediatrics, British Columbia Children’s Hospital, The University of British ColumbiaDepartment of Pediatrics, British Columbia Children’s Hospital, The University of British ColumbiaDepartment of Pediatrics, British Columbia Children’s Hospital, The University of British ColumbiaDepartment of Pediatrics, British Columbia Children’s Hospital, The University of British ColumbiaDepartment of Pediatrics, British Columbia Children’s Hospital, The University of British ColumbiaAbstract Background KRAS (KRAS proto-oncogene, GTPase; OMIM: 190,070) encodes one of three small guanosine triphosphatase proteins belonging to the RAS family. This group of proteins is responsible for cell proliferation, differentiation and inhibition of apoptosis. Gain-of-function variants in KRAS are commonly found in human cancers. Non-malignant somatic KRAS variants underlie a subset of RAS-associated autoimmune leukoproliferative disorders (RALD). RALD is characterized by splenomegaly, persistent monocytosis, hypergammaglobulinemia and cytopenia, but can also include autoimmune features and lymphadenopathy. In this report, we describe a non-malignant somatic variant in KRAS with prominent clinical features of massive splenomegaly, thrombocytopenia and lymphopenia. Case presentation A now-11-year-old girl presented in early childhood with easy bruising and bleeding, but had an otherwise unremarkable medical history. After consulting for the first time at 5 years of age, she was discovered to have massive splenomegaly. Clinical follow-up revealed thrombocytopenia, lymphopenia and increased polyclonal immunoglobulins and C-reactive protein. The patient had an unremarkable bone marrow biopsy, flow cytometry showed no indication of expanded double negative T-cells, while malignancy and storage disorders were also excluded. When the patient was 8 years old, whole exome sequencing performed on DNA derived from whole blood revealed a heterozygous gain-of-function variant in KRAS (NM_004985.5:c.37G > T; (p.G13C)). The variant was absent from DNA derived from a buccal swab and was thus determined to be somatic. Conclusions This case of idiopathic splenomegaly in childhood due to a somatic variant in KRAS expands our understanding of the clinical spectrum of RAS-associated autoimmune leukoproliferative disorder and emphasizes the value of securing a molecular diagnosis in children with unusual early-onset presentations with a suspected monogenic origin.https://doi.org/10.1186/s12887-021-02508-3RAS-associated lymphoproliferative diseaseKRASSplenomegalyCase report |
| spellingShingle | Geraldine Blanchard-Rohner Robert J. Ragotte Anne K. Junker Mehul Sharma Kate L. Del Bel Henry Y. Lu Stephanie Erdle Alanna Chomyn Harinder Gill Lori B. Tucker Richard A. Schreiber Jacob Rozmus Catherine M. Biggs Kyla J. Hildebrand John Wu Sylvia Stockler-Ipsiroglu Stuart E. Turvey Idiopathic splenomegaly in childhood and the spectrum of RAS-associated lymphoproliferative disease: a case report BMC Pediatrics RAS-associated lymphoproliferative disease KRAS Splenomegaly Case report |
| title | Idiopathic splenomegaly in childhood and the spectrum of RAS-associated lymphoproliferative disease: a case report |
| title_full | Idiopathic splenomegaly in childhood and the spectrum of RAS-associated lymphoproliferative disease: a case report |
| title_fullStr | Idiopathic splenomegaly in childhood and the spectrum of RAS-associated lymphoproliferative disease: a case report |
| title_full_unstemmed | Idiopathic splenomegaly in childhood and the spectrum of RAS-associated lymphoproliferative disease: a case report |
| title_short | Idiopathic splenomegaly in childhood and the spectrum of RAS-associated lymphoproliferative disease: a case report |
| title_sort | idiopathic splenomegaly in childhood and the spectrum of ras associated lymphoproliferative disease a case report |
| topic | RAS-associated lymphoproliferative disease KRAS Splenomegaly Case report |
| url | https://doi.org/10.1186/s12887-021-02508-3 |
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