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Mutations in the gene encoding plastin-3, PLS3, have recently been associated to severe primary osteoporosis. The molecular function of plastin-3 is not fully understood. Since PLS3 is located on the X chromosome, males are usually more severely affected than females. PLS3 mutations have thus far been reported in approximately 20 young patients with low bone mineral density (BMD). We describe an 8-year-old Greek boy with severe primary osteoporosis with multiple vertebral compression fractures and one low-energy long bone fracture. His clinical manifestations were consistent with osteogenesis imperfecta, including blue sclerae, joint hypermobility, low bone mineral density, kyphosis, bilateral conductive hearing loss, and mild dysmorphic features. The family history was negative for primary osteoporosis. COL1A1 and COL1A2 mutations were excluded by Sanger sequencing. However, Sanger sequencing of PLS3 led to the identification of a de novo frameshift deletion, NM_005032: c.1096_1100delAACTT, p.(Asn366Serfs*5), in exon 10 confirming the diagnosis of PLS3 osteoporosis. In conclusion, we describe a novel frameshift deletion in PLS3 causing severe primary osteoporosis in a boy. Our finding highlights the clinical overlap between type I collagen and PLS3-related skeletal fragility and underscores the importance of PLS3 screening in patients with multiple fractures to enable proper genetic counseling.

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Congenital insensitivity to pain with anhidrosis is a type IV hereditary sensory and autonomic neuropathy, presenting early in life. This disorder results from defective neural crest differentiation with loss of the first-order afferent system, which is responsible for sensations of pain and temperature; a neuronal loss in the sympathetic ganglia is also present. A case of a 33-year-old patient with congenital insensitivity to pain with anhidrosis is presented. From the time of birth, he did not sweat and did not respond to painful stimuli, although unexplained bouts of fever were often observed in infancy; an extensive workup during childhood helped establish the diagnosis. Throughout childhood and adulthood, the patient presented multiple infections and fractures in various sites of his body, growth disturbances, and avascular necrosis, and Charcot arthropathies and joint dislocations mainly affected his elbow and hip joint. At the final follow-up, at the age of 33 years, he was found to be obese, with a limited social life. A Charcot elbow restricted the activity of his left upper limb, and the dislocated hips combined with the instability of the ankle joints limited the ambulation distance. A specific treatment protocol has not been established in the literature; the main principles that can be applied in patients with normal intelligence include training programs to prevent self-mutilation and accidental injuries and an early diagnosis and treatment of the infections.