ESPE Abstracts

Introduction: Mutations of the PLS3 gene (MIM 300910), encoding plastin 3, are an extremely rare cause of osteogenesis imperfecta (OI). It has an X-linked inheritance and is characterized by early-onset osteoporosis and kyphosis, which can cause compression fractures, especially in the thoracic vertebrae. Although there are reports showing that bisphosphonates are effective in improving the bone mineral density of patients with PLS3 variants, data on treatment is limited.

Case: A 14.5-year-old male was referred due to kyphosis, and back and low back pain. On examination, his height was 150.8 cm (-2.1 SD), weight was 59 kg (0 SD), and mid-parental height was 170.3 cm (-0.9 SD). His body proportions were normal and he had significant thoracic kypho-scoliosis. He had white sclera, no joint laxity, and normal tooth structure. Puberty examination was compatible with Tanner stage-3. He had a history of forearm fracture due to a fall at the age of 11 years. His family reported that his uncles and cousins had kyphosis, and there were short individuals on his mother's side. Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH), 25-hydroxy-vitamin-D, insulin-like growth factor (IGF) 1 and IGF binding protein 3 values were within normal limits. Spinal MRI revealed platyspondyly and loss of vertebral height at the thoracic and lumbar vertebrae. Lumbar bone densitometry (BMD) showed low BMD (L1-L4 0.504 g/cm2, z-score -2.5). He received two courses of pamidronate (0.5 mg/kg over three days) with an interval of nine months. He experienced severe hypocalcemia (Calcium:6.5 mg/dL) and secondary hyperparathyroidism (PTH:513 pg/mL) after the first treatment. The patient reported a decrease in complaints decreased during follow-up and he exceeded mid-parental height (171.4 cm, -0.4 SD). His BMDs improved in the first and second years of treatment (L1-L4: 0.741 g/cm2, z-score: -1.6 and L1-L4: 0.879 g/cm2, z-score: -0.4, respectively). On next-generation sequencing, a c.1444G>A (p.G482R) (p.Gly482Arg) hemizygous variant was detected in PLS3, which has not been previously reported and was classified as highly pathogenic (American College of Medical Genetics criteria). The same variant was also detected in his mother.

Conclusion: PLS3 mutation screening should be considered in individuals with kypho-scoliosis with an X-linked inheritance pattern, fracture history and prominent vertebral involvement. Although bisphosphonates may help reduce symptoms and improve BMD, large observational and interventional studies would be needed to identify effective treatments, but given the rarity of the condition, publication of individual case reports will add to the available evidence.