Department of Medical and Surgical Sciences of the Mothers, Children and Adults, Post Graduate School of Paediatrics, University of Modena and Reggio Emilia, Modena, Italy.
Neonatology Unit, Mother-Child Department, University Hospital of Modena, Modena, Italy.
Pediatrics. 2022 Jan 1;149(1). doi: 10.1542/peds.2021-052411.
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.
欧扪综合征（OS）是一种罕见的严重联合免疫缺陷的变体，其特征是易发生严重机会性感染和特殊表现，如蛋白丢失性红皮病、脱发、肝脾肿大、淋巴结病和严重腹泻。该病的典型形式是由重组激活基因（RAG1 和 RAG2）的低功能突变引起的，这些基因在启动导致淋巴细胞和免疫球蛋白受体形成的分子过程中至关重要。受影响的患者缺乏 B 细胞，而自身反应性寡克隆 T 细胞浸润皮肤、肠道、脾脏和肝脏。在没有造血干细胞移植的情况下，OS 患者通常由于机会性感染而在早期夭折。OS 的发病率估计为 <1/1000000；然而，实际频率难以确定。我们报告了 2 例由 RAG1 基因中的纯合框移突变（NM_000448.3：c.519delT，p.E174Sfs*26）引起的 OS 同胞受累病例，表现为非免疫性胎儿水肿（NIHF）。据我们所知，这是 OS 与 NIHF 首次报道的关联。NIHF 特指胎儿存在≥2 个异常液体积聚，没有红细胞同种免疫。NIHF 与广泛的病理学相关；然而，在约 20%的病例中，主要原因仍不清楚。了解 NIHF 的病因对于指导临床管理、确定预后以及向父母告知复发风险至关重要。我们的病例有助于扩大 OS 表现的范围，并强调在其他原因不明的 NIHF 病例中进行全面免疫和遗传检查的重要性。
