Previously Unreported TMEM38B Variant in Osteogenesis Imperfecta Type XIV: A Case Report and Systematic Review of the Literature

Osteogenesis imperfecta (OI) type XIV is a rare recessive disorder caused by TMEM38B pathogenic variants that disrupt an endoplasmic reticulum protein essential for calcium homeostasis and bone mineralization. This leads to severe bone fragility, early-onset fractures, skeletal deformities, low bone mass, scoliosis, and variable features like blue sclerae or dental abnormalities. We present a case report of a 21-year-old Italian male with a novel homozygous TMEM38B splice variant (c.112 + 1G > T), detailing the clinical presentation, genetic findings, and therapeutic outcomes. The patient exhibited multiple skeletal deformities and showed a moderate response to bisphosphonate therapy (neridronate). In addition, a systematic review of PubMed and Scopus identified 12 relevant studies from an initial set of 82 publications, encompassing data from 56 patients diagnosed with OI type XIV. Unlike classical collagen-related OI, TMEM38B-related OI necessitates genetic screening beyond classical collagen genes (COL1A1 and COL1A2). While bisphosphonates provide some clinical benefit, persistent fractures underscore the need for long-term management and innovative therapies. This case report and systematic review enhance understanding of OI type XIV and underscore the clinical importance of TMEM38B variants in bone fragility disorders.