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Background Mpox virus is a double-stranded DNA virus of the Orthopoxvirus genus of the Poxviridae family. Two genetic Mpox clades have been characterised: Central African (clade I) and West African (clade II).After the first cases described in DRC in the 1970s, in 2022 the WHO reported that Mpox was endemic in several African countries; that same year, a global multi-country outbreak was described. Most patients reported high-risk sexual behaviour as a potential risk factor, but subsequent household transmission has also been described, even to children; perinatal transmission was observed, too.Case Series We describe a familial cluster of Mpox clade IIb (lineage A.2.2), involving five people ( figure 1).The index case, a 38-year-old man infected after condomless sexual intercourse in Nigeria, presented with extensive genital and cutaneous lesions. Orthopoxvirus DNA was detected in a pharyngeal swab, a penile lesion swab, swabs of the cutaneous vesicles, and blood samples. He received 20 days of tecovirimat and required penile degloving surgery with subcutaneous curettage and removal of necrotic tissue, and subsequent penile reconstruction.His 42-year-old pregnant wife developed mild mucocutaneous lesions around ten days after giving birth, and tested positive in a pharyngeal swab, blood sample, genital vesicle swab, urine sample, and vaginal swab; she was treated with 14 days of tecovirimat with full recovery.Their 18-year-old daughter only tested positive for Orthopoxvirus on a pharyngeal swab. She started tecovirimat, which was stopped after 3 days due to lack of clinical signs of infection.The 2-year-old daughter developed limited skin lesions but severe ocular involvement with conjunctivitis, orbital pseudopapillitis and preseptal pseudocellulitis of the right eye, successfully treated with systemic tecovirimat and topical cidofovir. Orthopoxvirus DNA was found on a pharyngeal swab, ocular swab and swab of the cutaneous vesicles.The 10-day-old newborn, infected at birth, presented with cutaneous disease and mild conjunctivitis and recovered after oral tecovirimat. Qualitative testing for Orthopoxvirus DNA was positive on a pharyngeal swab, blood sample, ocular swab and swab of the cutaneous vesicles.All patients achieved complete clinical resolution.Conclusions Even though incidence in non-endemic countries is now decreasing, Mpox diagnosis must be taken into account in patients with risk factors that present with suggestive signs and symptoms; their household contacts should be closely monitored for the development of clinical manifestations, especially children, who are more likely to experiment severe disease.Abstract CC3 Figure 1Phylogenetic analysis of the cluster