Osteoporosis Caused by Monoallelic Variant of WNT1 Gene in Four Pediatric Patients.

Pediatric patients of autosomal dominant early onset osteoporosis conferred by heterozygous mutation in the WNT1 (OMIM: 615221) were rarely reported, and therapy in pediatrics is relatively inexperienced. The clinical and genotypic characteristics and treatment process of four children with osteoporosis caused by WNT1 monoallelic variation were analyzed. The patients admitted from June 2023 to January 2024. All patients presented multiple vertebral compression fracture, two of them experienced recurrent peripheral fragility fractures. The age of the first fractures occur between 2 years and 12 years. Lumber BMD by dual-energy X-ray absorptiometry were decreased (height adjusted z score of -8.06 to -3.50). Four monoallelic variants in WNT1 (c.505G>T, c.616G>A, c.677C>T and c. 506G>A with transcript ID. NM_005430.4) were identified in the probands, and relatives carrying mutations presented with a bone phenotype, consistent with autosomal dominant inheritance. Novel variant c.616G>A was analyzed by 3D protein structural modeling. Subsequent to the treatment of zelodronic acid on all four patients, lumbar BMD improvement by 0.061-0.251 g/cm. Our data showed that the age of onset of osteoporosis by monoallelic variants in WNT1 is significantly earlier than the age of onset in the general population. Severe osteoporosis is also exhibited in pediatric patients, not just in aging patients with WNT1 variant. Zoledronic acid treatment is effective in short-term observation for pediatric patients with improvement of bone pain and BMD, and no more facture during treatment.