Case Reports Journal Article Epublish 3 citations
PubMed: 40510867 DOI: 10.1093/jbmrpl/ziaf084
Assessment and treatment of osteoporosis in a patient with a neurodevelopmental disorder caused by a RNU4-2 pathogenic variant (ReNU syndrome).
JBMR Plus 9(7):ziaf084
Authors: Tess Holling, Simon von Kroge, Laura Hecher, Michael Amling, Thorsten Schinke, Kerstin Kutsche, Ralf Oheim
Affiliations
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
- Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
- Department of Pediatrics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
- German Center for Child and Adolescent Health (DZKJ), partner site Hamburg, 20246 Hamburg, Germany.
Abstract
A 16-yr-old male with a genetically undiagnosed neurodevelopmental disorder (NDD) was admitted to our outpatient clinic for skeletal assessment. DXA and HR-pQCT showed a severely reduced BMD and a pronounced reduction of trabecular and cortical bone mass. Lateral vertebral assessment identified multiple previously unrecognized vertebral fractures of the thoracic and lumbar spine. Laboratory tests indicated an activated bone turnover, which was confirmed by an increased number of osteoclasts and osteoblasts in an undecalcified tibia biopsy of the patient. Treatment of the severe osteoporosis was initiated with neridronate. Trio exome sequencing in the patient and healthy parents did not uncover a genetic cause of the disease. Importantly, however, targeted sequencing of the RNU4-2 gene, which encodes the U4 small nuclear RNA (a major component of the splicing machinery), identified a heterozygous causative variant in the patient. This led to the molecular diagnosis of ReNU syndrome. RNU4-2 pathogenic variants underlie a NDD with multisystemic involvement, including skeletal abnormalities. Therefore, this case not only underlines the relevance of osteologic assessment and therapy in individuals with NDDs, but also highlights the necessity of future research efforts to elucidate the bone pathologies in ReNU syndrome.
MeSH
Genes, Neurodevelopmental Disorders, Osteoporosis, Spliceosomes, Therapeutics, Neurodevelopment