Omenn syndrome (OS) is a rare variant of severe combined immunodeficiency characterized by susceptibility to severe opportunistic infections and peculiar manifestations, such as protein-losing erythroderma, alopecia, hepatosplenomegaly, lymphadenopathies, and severe diarrhea. The typical form of the disease is caused by hypomorphic mutation of the recombination-activating genes (RAG1 and RAG2), which are critical in initiating the molecular processes leading to lymphocyte and immunoglobulin receptor formation. Affected patients lack B cells, whereas autoreactive oligoclonal T cells infiltrate the skin, gut, spleen, and liver. In the absence of hematopoietic stem cell transplantation, patients with OS usually succumb early in life because of opportunistic infections. The incidence of OS is estimated to be <1 per 1 000 000; however, the actual frequency is difficult to ascertain. We report 2 siblings affected by OS due to a homozygous frameshift mutation (NM_000448.3:c.519delT, p.E174Sfs*26) in the RAG1 gene presenting with nonimmune hydrops fetalis (NIHF). To the best of our knowledge, this is the first reported association between OS and NIHF. NIHF specifically refers to the presence of ≥2 abnormal fluid collections in the fetus, without red blood cell alloimmunization. A broad spectrum of pathologies is associated with NIHF; however, in ∼20% of the cases, the primary cause remains unclear. Understanding the etiology of NIHF is essential for guiding clinical management, determining prognosis, and informing parents regarding recurrence risk. Our case contributes to expanding the spectrum of OS presentation and highlights the importance of a complete immunologic and genetic workup in otherwise unexplained cases of NIHF.
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January 2022
Case Reports|
December 10 2021
Omenn Syndrome due to RAG1 Mutation Presenting With Nonimmune Hydrops Fetalis in Two Siblings
Lara Valeri, MD;
Lara Valeri, MD
aDepartment of Medical and Surgical Sciences of the Mothers, Children and Adults, Post Graduate School of Paediatrics, University of Modena and Reggio Emilia, Modena, Italy
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Licia Lugli, MD;
Licia Lugli, MD
bNeonatology Unit, Mother-Child Department, University Hospital of Modena, Modena, Italy
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Lorenzo Iughetti, MD;
Lorenzo Iughetti, MD
aDepartment of Medical and Surgical Sciences of the Mothers, Children and Adults, Post Graduate School of Paediatrics, University of Modena and Reggio Emilia, Modena, Italy
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Annarosa Soresina, MD;
Annarosa Soresina, MD
cUnit of Pediatric Immunology, Pediatrics Clinic, ASST-Spedali Civili of Brescia, Brescia, Italy
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Silvia Giliani, PhD;
Silvia Giliani, PhD
dCytogenetic and Medical Genetics Unit, “A. Nocivelli” Institute for Molecular Medicine, Spedali Civili Hospital, Brescia, Italy
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Fulvio Porta, MD;
Fulvio Porta, MD
ePediatric Oncohematology and Bone Marrow Transplant Unit, Children’s Hospital, Spedali Civili, Brescia, Italy
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Alberto Berardi, MD
bNeonatology Unit, Mother-Child Department, University Hospital of Modena, Modena, Italy
Address correspondence to Alberto Berardi, Neonatology Unit, Mother-Child Department, University Hospital of Modena, Via del Pozzo 71, 41124 Modena, Italy. E-mail: alberto.berardi@unimore.it
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FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
Address correspondence to Alberto Berardi, Neonatology Unit, Mother-Child Department, University Hospital of Modena, Via del Pozzo 71, 41124 Modena, Italy. E-mail: alberto.berardi@unimore.it
Pediatrics (2022) 149 (1): e2021052411.
Article history
Accepted:
August 23 2021
Citation
Lara Valeri, Licia Lugli, Lorenzo Iughetti, Annarosa Soresina, Silvia Giliani, Fulvio Porta, Alberto Berardi; Omenn Syndrome due to RAG1 Mutation Presenting With Nonimmune Hydrops Fetalis in Two Siblings. Pediatrics January 2022; 149 (1): e2021052411. 10.1542/peds.2021-052411
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