Chondrodysplasia and growth failure in children after early hematopoietic stem cell transplantation for non‐oncologic disorders
| Autor: | Ataf Sabir, Andrea Superti-Furga, Belinda Campos-Xavier, Lorenzo D. Botto, C. Putti, Luisa Bonafé, Andrea Finocchi, Yasemin Alanay, Wendy D Jones, Chiara Mozzato, Daniela Zuccarello, Birgit Zirn, Christof M. Kramm, Ingrid Kühnle, Marie Meeths, Melita Irving, Laura Mazzanti, Ann Nordgren, Jan-Inge Henter, Giedre Grigelioniene, Gen Nishimura, Caterina Cancrini, Anna Hammarsjö, Emanuela Scarano, Sheila Unger, R. Bergamaschi, Birgit Borgström |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Pediatrics medicine.medical_specialty medicine.medical_treatment Hematopoietic stem cell transplantation Osteochondrodysplasias Short stature Lymphohistiocytosis Hemophagocytic 03 medical and health sciences 0302 clinical medicine Genetics medicine Humans UNC13D Child Genetics (clinical) 030304 developmental biology 0303 health sciences Hemophagocytic lymphohistiocytosis Spondyloepimetaphyseal dysplasia Severe combined immunodeficiency Perforin business.industry Hematopoietic Stem Cell Transplantation Membrane Proteins medicine.disease Settore MED/38 Omenn syndrome 3. Good health Treatment Outcome Child Preschool 030220 oncology & carcinogenesis Female Stem cell medicine.symptom business |
| Zdroj: | American Journal of Medical Genetics Part A. 185:517-527 |
| ISSN: | 1552-4833 1552-4825 |
| DOI: | 10.1002/ajmg.a.62021 |
| Popis: | Bone dysplasias (osteochondrodysplasias) are a large group of conditions associated with short stature, skeletal disproportion, and radiographic abnormalities of skeletal elements. Nearly all are genetic in origin. We report a series of seven children with similar findings of chondrodysplasia and growth failure following early hematopoietic stem cell transplantation (HSCT) for pediatric non-oncologic disease: hemophagocytic lymphohistiocytosis or HLH (five children, three with biallelic HLH-associated variants [in PRF1 and UNC13D] and one with HLH secondary to visceral Leishmaniasis), one child with severe combined immunodeficiency and one with Omenn syndrome (both children had biallelic RAG1 pathogenic variants). All children had normal growth and no sign of chondrodysplasia at birth and prior to their primary disease. After HSCT, all children developed growth failure, with standard deviation scores for height at or below -3. Radiographically, all children had changes in the spine, metaphyses and epiphyses, compatible with a spondyloepimetaphyseal dysplasia. Genomic sequencing failed to detect pathogenic variants in genes associated with osteochondrodysplasias. We propose that such chondrodysplasia with growth failure is a novel, rare, but clinically important complication following early HSCT for non-oncologic pediatric diseases. The pathogenesis is unknown but could possibly involve loss or perturbation of the cartilage-bone stem cell population. |
| Databáze: | OpenAIRE |
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