The landscape of pediatric Diamond-Blackfan anemia in Switzerland: genotype and phenotype characteristics

Diamond-Blackfan anemia (DBA) is caused mainly by genetic mutations in large ( RPL ) or small ribosomal subunit genes ( RPS) and presents with macrocytic anemia and congenital malformations. Clinical differences between genotypes are insufficiently understood. The aim of this study was to assess clinical features, treatment strategies, and genotypes in the Swiss pediatric DBA population. We retrospectively reviewed medical charts of pediatric patients with DBA in Switzerland and stratified patients by RPL versus RPS mutations. We report 17 DBA patients in Switzerland who were all genetically investigated. In our cohort, patients showed a wide spectrum of clinical presentations and treatment needs. We found a high proportion of physical malformations (77%) including lower limb (17%) and anorectal (12%) malformations. The two patients with anorectal malformations presented both with antepositioning of the anus needing surgery within the first 15 months of life. One of these patients had sphincteric dysfunction, the other coccygeal agenesis. We found that included patients with an RPL mutation more frequently tended to have physical malformations and a milder anemia compared to patients with an RPS mutation (median hemoglobin at diagnosis 76 g/l versus 22 g/l). Conclusion: We illustrate the wide clinical and genetic spectrum of DBA in Switzerland. Our findings highlight the need to take this diagnosis into consideration in patients with severe anemia but also in patients with mild anemia where malformations are present. Lower limb and anorectal malformation extend the spectrum of DBA-associated malformations. What is Known? • There is a large variation in the phenotype of Diamond-Blackfan Anemia (DBA) and diversity of genetic mutations. • Malformation of the upper limbs, head and face, heart, and genitourinary system is frequently identified. What is New? • Patients with lower limb and anorectal malformations were repetitively found in our cohort enlarging the clinical spectrum of malformations. • We show two patients of the same family with a DBA-like condition where the same RPL17 variant was identified.