Objective: To study the clinical features and genetic mutations of children with Shwachman-Diamond syndrome (SDS) and malignant myeloid transformation.
Methods: Next-generation sequencing was used to analyze the gene mutations in 11 SDS children with malignant myeloid transformation, and their clinical features and genetic mutations were analyzed.
Results: Of the 11 children with SDS, 9 (82%) presented with refractory cytopenia of childhood (RCC), 1 (9%) had myelodysplastic syndrome with excess blasts (MDS-EB), and 1 (9%) had acute myeloid leukemia with myelodysplasia-related changes (AML-MRC). The median age of onset of malignant myeloid transformation was 48 months (ranged 7 months to 14 years). Of the 11 children, 45% had abnormalities in the hematological system alone. Mutations of the SBDS gene were detected in all 11 children, among whom 5 (45%) had c.258+2T>C homozygous mutation and 3 (27%) had c.184A>T+c.258+2T>C compound heterozygous mutation. The new mutations of the SBDS gene, c.634_635insAACATACCTGT+c.637_638delGA and c.8T>C, were rated as "pathogenic" and "possibly pathogenic" respectively. The 3-year predicted overall survival rates of children transformed to RCC and MDS-EB/AML-MRC were 100% and 0% respectively (P=0.001).
Conclusions: SDS children may have hematological system symptoms as the only manifestation, which needs to be taken seriously in clinical practice. The type of malignant transformation is associated with prognosis.
目的: 探讨伴髓系恶性转化的Shwachman-Diamond综合征(SDS)患儿的临床特征及基因突变情况。
方法: 采用二代测序方法检测11例伴髓系恶性转化的SDS患儿的基因突变情况，分析患儿的临床特征和基因突变谱。
结果: 11例SDS患儿中，9例(82%)表现为儿童难治性血细胞减少(RCC)，1例(9%)为骨髓增生异常综合征(MDS)伴原始细胞增多(MDS-EB)，1例(9%)为急性髓系白血病伴MDS相关改变(AML-MRC)。发生髓系恶性转化的中位年龄为48个月(范围：7个月~14岁)。5例(45%)患儿表现为单纯的血液系统异常。所有患儿均检测到SBDS基因突变，常见的突变形式为c.258+2T > C纯合突变(5例，45%)和c.184A > T+c.258+2T > C复合杂合突变(3例，27%)。SBDS基因新变异c.634_635insAACATACCTGT+c.637_638delGA和c.8T > C分别评级为"致病的"和"可能致病的"。转化为RCC和MDS-EB/AML-MRC的患儿3年预期总体生存率分别为100%、0%(P=0.001)。
结论: SDS患儿可能以血液系统症状为唯一表现，临床应引起重视。恶性转化的类型与预后相关。