Endocrine Abstracts

JOINT2424

A 10-year-old girl was referred to the paediatric rare bone disease service by neurology for persistent leg pain, stiffness, and an undiagnosed condition despite extensive evaluation. Born at term following an uneventful pregnancy, she met early milestones and walked independently at 12 months. Symptoms began at 2 years of age with unsteadiness and frequent falls. By 3 years of age, she struggled with running and fatigued easily. By 6 years of age, she had difficulty climbing stairs, used a one-foot-at-a-time approach, and could not jump. Her dystonia primarily affected her lower limbs, with no family history of similar conditions. Brain and spine MRIs were normal. At age 7, she was referred to the complex movement disorder service, initially suspected of primary dystonia. Extensive metabolic, neuromuscular, and genetic tests were inconclusive, and nerve conduction studies were normal. Due to needle phobia, sedation or general anaesthesia was required for testing. Multiple dystonia medications, including L-Dopa, clonazepam, and gabapentin, failed and caused side effects like anxiety, mood disturbances, and suicidal ideation. She was also enrolled in the 100, 000 Genomes Project. By age 9, her condition worsened; she developed a waddling gait with foot clawing and required a wheelchair for long distances. A paediatric neurologist questioned the dystonia diagnosis, and deep brain stimulation was not pursued. Following referral to rare bone disease service, radiographs and MRI of the lower limbs were obtained and these revealed cortical thickening, Erlenmeyer flask deformity of the femora, and bone marrow oedema, suggesting Camurati-Engelmann disease (CES). Whole genome sequencing confirmed a de novo heterozygous pathogenic TGFB1 missense variant, confirming CES. Her current management includes physiotherapy, hydrotherapy, regular analgesia, heat pads, and activity pacing. NSAIDs help control pain, with prednisolone or losartan as potential options. She is growing well and has entered puberty without issues. Audiology, ophthalmology, and DEXA scans remain normal, with a lumbar spine and Total Body Less Head BMD z-score of -0. 3. CES is a rare autosomal dominant disorder caused by TGFB1 mutations, leading to progressive diaphyseal dysplasia with bone pain, muscle weakness, and waddling gait due to cortical thickening of long bones. Skull thickening can cause CNS complications such as increased intracranial pressure, headaches, optic nerve compression, and cranial nerve dysfunction. CES should be considered in children with unexplained limb pain and stiffness, particularly with radiological features like cortical thickening, Erlenmeyer flask deformity, and bone marrow narrowing. Early diagnosis prevents unnecessary investigations and ineffective treatments.