Activated PI3K δ syndrome (APDS) is a primary immunodeficiency caused by heterogeneous germline gain-of-function mutations which ultimately lead to the hyperactivation of the phosphoinositide-3-kinase δ (PI3K δ). PI3K δ exists as a heterodimer composed of a catalytic and a regulatory subunit. APDS type 2 is caused by mutations in the PIK3R1 gene affecting the p85α regulatory subunit. SHORT syndrome is a rare multisystem disorder characterized by short stature, hyperextensible joints, ocular depression, Rieger anomaly, and tooth eruption delay. The primary causes of SHORT syndrome are heterozygous loss-of-function mutations in the PIK3R1 gene. The combination of APDS2 and SHORT syndrome is rare, with few cases reported to date. Here we describe a 17-year-old female with phenotypic features consistent with SHORT syndrome and history of sinopulmonary infections and hypogammaglobulinemia. Invitae immunodeficiency panel genetic testing revealed a pathogenic loss-of-function variant in an intronic splice site in the gene PIK3R1 (c.1425 + 1G > C). This pathogenic variant had been previously associated with APDS2; however, it had not been associated with SHORT syndrome. The exact mechanisms linking both conditions are yet to be identified. This case report emphasizes the importance of screening for comorbidities associated with SHORT syndrome in APDS2 patients and vice versa.

激活的 PI3K δ 综合征 (APDS) 是由异质种系功能获得性突变引起的原发性免疫缺陷，最终导致磷酸肌醇 3-激酶 δ (PI3K δ) 过度活化。PI3K δ 以由催化亚基和调节亚基组成的异二聚体形式存在。APDS 2 型是由影响 p85α 调节亚基的PIK3R1基因突变引起的。SHORT 综合征是一种罕见的多系统疾病，其特征是身材矮小、关节过度伸展、眼球凹陷、Rieger 异常和牙齿萌出延迟。SHORT 综合征的主要原因是PIK3R1中的杂合性功能丧失突变基因。APDS2 和 SHORT 综合征的组合很少见，迄今为止报道的病例很少。在这里，我们描述了一名 17 岁女性，其表型特征与 SHORT 综合征一致，并且有窦肺感染和低丙种球蛋白血症的病史。Invitae 免疫缺陷面板基因检测显示基因PIK3R1 (c.1425 + 1G > C)的内含子剪接位点存在致病性功能丧失变异。这种致病性变异以前与 APDS2 相关；然而，它与 SHORT 综合征无关。尚未确定将这两种情况联系起来的确切机制。本病例报告强调了筛查与 APDS2 患者 SHORT 综合征相关的合并症的重要性，反之亦然。