ESPE Abstracts

Introduction: Bone fragility or predisposition to fractures with low-impact energy is a rare but potentially limiting condition. Variations in PLS3 gene are a cause of monogenic osteoporosis due to the alteration of osteoclast and osteocyte function and bone mineralization. It is characterized by early-onset osteoporosis, peripheral fractures, vertebral compression fractures and thoracic kyphosis. Due to its X-linked inheritance, the phenotype is more severe in males. We report an adolescent with severe multiple vertebral fractures associated with a novel pathogenic variant in the PLS3 gene.

Case Report: A 11-years old male consulting due to chronic lumbar pain (last six months), which limited normal life activity. He had a history of five previous non-simultaneous long bone fractures. He denied high energy impacts. He was born at 36-week gestational age with a normal birth length (+1.41 DS) and weight (+2.2 DS). He received Vitamin D prophylaxis the first year of life. Psichomotor development was normal and had no chronic treatment. His father and mother were both healthy with heights of 186 cm and 168,5 cm respectively and denied consanguineity. Non familiar history of fractures, joint or vertebral column problems. Our patient´s height and weight were normal, but he presented a wide arm-span (103%) and a reduced trunk height to standing height ratio (-0.27 DE). He had hypoplastic tooth enamel and hyperkiphosis. On the contrary, he had white sclarae, and no dismorphic features or joint hyperlaxity. X-ray and magnetic resonance (MR) revealed dorsolumbar shortened biconcave vertebrae and multiple fractured vertebrae. The lumbar and neck bone mineral density (BMD) was under normal values for sex, age and height. Calcium, phosphate, magnesium, 25-hydroxyvitamin D, intact parathiroid hormone, phosphatase alkaline and urinary phosphoethanolamine levels were in normal range by sex and age. Only procollagen type I N-terminal propeptide, osteocalcin and urinary calcium/creatinine were increased at diagnosis (1100 ng/dl, 85.8 ng/dl and 400 mg/g respectively). The bone fragility NGS panel identified a hemizygous variant (c.1761-1G>T) at intron 15 of PLS3 gene. It is located in a canonical splice acceptor of intron 15 and could predict an abnormal RNA processing and an aberrant protein and was classified as pathogenic. Segregation study showed that same variant in his mother.

Comments: Patients with multiple fractures or chronic bone pain need to be assessed for bone fragility entities. A shortened trunk, increased arm-span or low sitting height/standing height ratio are alarming signs of vertebral problems.