Clinical features and gene mutations of children with Shwachman-Diamond syndrome and malignant myeloid transformation / 中国当代儿科杂志

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.

Clinical features, diagnosis, and treatment of Chinese children with Shwachman-Diamond syndrome / 中国当代儿科杂志

In order to clearly define the features of Shwachman-Diamond syndrome (SDS) in Chinese children, this article analyzes and summarizes the epidemiology, clinical features, and key points in the diagnosis and treatment of SDS in Chinese children with review of the clinical data of 27 children with SDS from related articles published previously. A comparative analysis was made between the Chinese and international data related to childhood SDS. The results showed a male/female ratio of about 2:1 in the Chinese children with SDS, with an age of onset of <1 month to 5 years (median 1 month) and an age of 3 months to 12 years (median 12 months) at the time of confirmed diagnosis. Reductions in peripheral blood cells due to myelopoiesis inhibition were observed in all 27 children with SDS, among whom 93% had neutropenia. Chronic diarrhea (85%), liver damage (78%), and short stature (83%) were the three main clinical features of SDS. Supplementation of pancreatin and component blood transfusion may temporarily alleviate the disease, while allogeneic hematopoietic stem cell transplantation is still an effective radical treatment. The comparative analysis of the Chinese and oversea data showed that compared with those in the European and American countries, the children with SDS in China had significantly higher incidence rates of chronic diarrhea, reductions in peripheral blood cells (three lineages), and liver damage, and there were also differences in the type of mutant genes.