👤 Jiska Ristori

Deficiency of the 17β-hydroxysteroid dehydrogenase type 3 (17 β-HSD3) is a rare autosomal recessive 46,XY Difference of sex development (DSD), resulting from pathogenetic variants in the HSD17B3 gene, which lead to absent or reduced ability to convert Δ4-androstenedione to testosterone in the fetal testes. This study aimed to present the clinical and genetic characteristics of an Italian patient receiving a diagnosis of 17 β-HSD3 deficiency in adulthood. The patient was raised as female and underwent early surgical interventions to correct virilized genitalia, leading to a significant sexual distress. At the time of the referral, a 20-gene Next Generation Sequencing custom-panel for DSD was performed on patient's genomic DNA. A novel compound heterozygous mutation in HSD17B3 gene was identified, detecting a new variant (c.257₂₆₅delAGGCCATTG, p.) CONCLUSION: Novel genotype causing 17 β-HSD3 deficiency is presented. Furthermore, the patient's clinical history stresses the importance to actively involve these individuals in the decision-making process avoiding surgical intervention when the patient is not able to give fully informed consent. Cocchetti C, Baldinotti F, Romani A, et al. A Novel Compound Heterozygous Mutation of HSD17B3 Gene Identified in a Patient With 46,XY Difference of Sexual Development. Sex Med 2022;10:100522. Show less

Hereditary multiple exostoses (HME) is an inherited genetic condition characterized by the presence of multiple exostoses (osteochondromas). MHE is a relatively rare autosomal dominant disorder, mainly caused by loss of function mutations in two genes: exostosin-1 (EXT1) and exostosin-2 (EXT2). These genes are linked to heparan sulfate (HS) synthesis, but the specific molecular mechanism leading to the disruption of the cartilage structure and the consequent exostoses formation is still not resolved. The aim of this paper is to encounter the main aspects of HME reviewing the literature, in order to improve clinical features and evolution, and the metabolic-pathogenetic mechanisms underlying. Although MHE may be asymptomatic, a wide spectrum of clinical manifestations is found in paediatric patients with this disorder. Pain is experienced by the majority of patients, even restricted motion of the joint is often encountered. Sometimes exostoses can interfere with normal development of the growth plate, giving rise to limb deformities, low stature and scoliosis. Other many neurovascular and associated disorders can lead to surgery. The most feared complication is the malignant transformation of an existing osteochondroma into a secondary peripheral chondrosarcoma, during adulthood. The therapeutic approach to HME is substantially surgical, whereas the medical one is still at an experimental level. In conclusion, HME is a complex disease where the paediatrician, the geneticist and the orthopaedic surgeon play an interchangeable role in diagnosis, research and therapy. We are waiting for new studies able to explain better the role of HS in signal transduction, because it plays a role in other bone and cartilage diseases (in particular malignant degeneration) as well as in skeletal embryology. Show less