Idiopathic splenomegaly in childhood and the spectrum of RAS-associated lymphoproliferative disease: a case report

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

doi:10.1186/s12887-021-02508-3

BMC Pediatrics (Jan 2021)

Idiopathic splenomegaly in childhood and the spectrum of RAS-associated lymphoproliferative disease: a case report

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

Affiliations

Geraldine Blanchard-Rohner: Department of Pediatrics, British Columbia Children’s Hospital, The University of British Columbia
Robert J. Ragotte: Jenner Institute, Nuffield Department of Medicine, University of Oxford
Anne K. Junker: Department of Pediatrics, British Columbia Children’s Hospital, The University of British Columbia
Mehul Sharma: Department of Pediatrics, British Columbia Children’s Hospital, The University of British Columbia
Kate L. Del Bel: Department of Pediatrics, British Columbia Children’s Hospital, The University of British Columbia
Henry Y. Lu: Department of Pediatrics, British Columbia Children’s Hospital, The University of British Columbia
Stephanie Erdle: Department of Pediatrics, British Columbia Children’s Hospital, The University of British Columbia
Alanna Chomyn: Department of Pediatrics, British Columbia Children’s Hospital, The University of British Columbia
Harinder Gill: Department of Medical Genetics, The University of British Columbia
Lori B. Tucker: Department of Pediatrics, British Columbia Children’s Hospital, The University of British Columbia
Richard A. Schreiber: Department of Pediatrics, British Columbia Children’s Hospital, The University of British Columbia
Jacob Rozmus: Department of Pediatrics, British Columbia Children’s Hospital, The University of British Columbia
Catherine M. Biggs: Department of Pediatrics, British Columbia Children’s Hospital, The University of British Columbia
Kyla J. Hildebrand: Department of Pediatrics, British Columbia Children’s Hospital, The University of British Columbia
John Wu: Department of Pediatrics, British Columbia Children’s Hospital, The University of British Columbia
Sylvia Stockler-Ipsiroglu: Department of Pediatrics, British Columbia Children’s Hospital, The University of British Columbia
Stuart E. Turvey: Department of Pediatrics, British Columbia Children’s Hospital, The University of British Columbia

DOI: https://doi.org/10.1186/s12887-021-02508-3
Journal volume & issue: Vol. 21, no. 1
pp. 1 – 4

Abstract

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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.

Published in BMC Pediatrics

ISSN: 1471-2431 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine: Pediatrics
Website: https://bmcpediatr.biomedcentral.com

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