With the inherent T-cell immunodeficiency of Schimke immune-osseous dysplasia (SIOD), the management of immunosuppressive therapy after transplantation and life-threatening infections remains a challenge. Here, we present a case of a child with SIOD who developed early-onset Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (PTLD) after kidney transplantation. PTLD frequently involves the gastrointestinal tract and solid allografts, while this case also involved the lungs, which is extremely rare. This case underscores the importance of considering PTLD in recipients with immunodeficiency, long-term immunosuppressive therapy, and EBV seronegativity. It also suggests low-dose immunotherapy and hematopoietic stem-cell transplantation for patients with SIOD.

Schimke immuno-osseous dysplasia (SIOD) is a hereditary autosomal-recessive multi-system disorder with early mortality. It has variable clinical presentations, mainly characterised by disproportional short stature, steroid-resistant nephrotic syndrome, spondyloepiphyseal dysplasia, and T-cell immunodeficiency. In the majority of cases, SIOD is caused by pathogenic sequence variants (PSVs) in the SMARCAL1 gene that encodes protein involved in chromatin remodelling. SIOD is an ultra-rare condition, with an incidence of ~1 per 1-3 million live births; data on its genetic and clinical features are scarce. We conducted a retrospective study of 21 paediatric patients with SIOD diagnosed in our centre during the years 2003-2023. The most common extra-renal clinical features were short stature, osseous dysplasia, multiple stigmas, and leukopenia. Proteinuria of varying severity was observed in 16 cases. The five-year overall survival rate (OS) was 89% (95% CI 77-100%), and the ten-year OS was 10%. Next-generation sequencing (NGS) revealed the following PSVs in SMARCAL1 in 19 patients: c.355_500del, c.2542G>T, c.2290C>T, c.2562del, c.2533_2534del, c.1582A>C, c.1933C>T, c.1010T>C, c.1736C>T, c.2070dup, c.2551A>T, c.2149_2150dup, c.939delC, and c.1451T>A; the most common was c.2542G>T, resulting in premature translation termination (p.E848*), and it was found in 14 patients either in a homozygous (four patients) or compound-heterozygous (10 patients) state. According to microsatellite analysis, it is a "founder mutation" in Russia.

We report a rare association between Schimke immune-osseous dysplasia and myasthenia gravis. Clinicians should be aware of potential autoimmune neuromuscular complications in SIOD, as early recognition and tailored immunosuppression may improve prognosis.

Schimke Immuno-Osseous Dysplasia Is a Rare Autosomal Recessive Multisystem Disorder Caused by Biallelic Pathogenic Variants in the SMARCAL1 Gene, Which Encodes a DNA Annealing Helicase Essential for Replication Fork Stability and Genomic Maintenance. Loss of SMARCAL1 Function Leads to Genomic Instability, Resulting in a Characteristic Clinical Triad of Disproportionate Short Stature, Steroid-Resistant Nephrotic Syndrome and Immunodeficiency. Kidney Transplantation Is the Standard Treatment for End-Stage Renal Disease in Schimke Immuno-Osseous Dysplasia. However, the Underlying Genomic Fragility and Immunodeficiency Heighten the Risk of Post-Transplant Complications, Particularly Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disorder. We Report the Case of a 7-Year-Old Girl With Genetically Confirmed Schimke Immuno-Osseous Dysplasia Who Developed Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma Eight Months Following Maternal Kidney Transplantation, Despite Reduced-Intensity Immunosuppression. Rituximab Therapy Resulted in Complete Remission, but Required the Withdrawal of all Immunosuppressive Agents, Thereby Posing a Risk of Kidney Graft Loss. In the Context of Primary Immunodeficiency and the Development of Post-Transplant Lymphoproliferative Disorder in Such a Setting, the Patient Subsequently Underwent Haploidentical Hematopoietic Stem Cell Transplantation From the Mother, Using an αβ T-Cell-Depleted Graft and a Nephrotoxicity-Sparing Conditioning Regimen. Full Donor Chimerism Was Achieved by Day 28. Immune Reconstitution Occurred Within One Year. At 27 Months After Hematopoietic Stem Cell Transplantation She Remains in Remission With Preserved Kidney Function and no Ongoing Immunosuppression. This Case Highlights the Feasibility of Haploidentical Hematopoietic Stem Cell Transplantation as a Curative Salvage Strategy for Immunosuppression-Free Survival After Kidney Transplantation in Patients With Schimke Immuno-Osseous Dysplasia.

Schimke immune-osseous dysplasia (SIOD) is a sporadic multi-system disorder mainly characterized by spondyloepiphyseal dysplasia, immune insufficiency, and renal failure. Little evidence is available regarding the dentofacial features of SIOD. This study presents the clinical course of a 16-year-old girl suffering from SIOD, focusing on her oral anomalies from her mixed to permanent dentition. After kidney transplantation and immune therapy, the patient discussed herein is supposed to live longer than a majority of the Schimke population. These findings might play a role in the earlier diagnosis of the syndrome and can better emphasize oral care throughout their lives. This is the first study that thoroughly discusses the dental anomalies of an SIOD patient from her mixed to permanent dentition.