A rare case of a young girl with genital manifestations of Proteus syndrome

A female aged 3 years presented with progressive clitoral and left lower limb enlargement, notably over the past year, and recent hearing reduction, with no birth abnormalities. Examination revealed asymmetric left lower limb enlargement with 4-cm length discrepancy and increased girth, epidermal nevi on the upper thighs and below the left knee (Fig. 1), and hypertrophied clitoris and the left buttock (Fig. 2); the labia, urethra, and vagina appeared normal. Blood workups were normal, the Barr body test confirmed female sex (XX), and renal ultrasonography demonstrated relative left kidney enlargement. The multidisciplinary team opted for conservative management. Clinical features guided diagnosis, with differentials including neurofibromatosis type 1, Klippel–Trenaunay syndrome, hemihyperplasia, and Parkes–Weber syndrome. Proteus syndrome is a rare, sporadic mosaic overgrowth disorder caused by postzygotic activating AKT1 gene mutation, characterized by progressive, asymmetric, disproportionate overgrowth of multiple tissues—particularly bone, connective tissue, skin, adipose tissue, and vascular structures—producing marked phenotypic variability and distortion.[1,2] Few cases with genital involvement in Proteus syndrome have been documented. This manifests as asymmetric external genital enlargement (penis, scrotum, labia, or clitoris), lipomatous or fibroadipose overgrowth, vascular malformations, and cutaneous lesions (epidermal nevi or cerebriform connective tissue nevi) in genital, perineal, or other regions.[1,3] Internal genital structures are rarely involved; functional, cosmetic, and psychosocial implications may necessitate individualized surgical management, ideally after growth stabilization.[4,5] This resembles other syndromes, with many cases likely missed as observed by Turner et al.[2] This case serves as a reminder to clinicians to rule out Proteus syndrome in cases with ambiguous genitalia.Figure 1.: The asymmetric left lower limb enlargement and epidermal nevi on both upper thighs and below the left knee in a female aged 3 years.Figure 2.: The perineal region. (A) Asymmetrically hypertrophied clitoris pointing rightward with pubic hair at Turner stage 1. (B) Relatively enlarged left buttock; the labia, urethra, and vagina appeared normal; some parts are not marked in the current image.Acknowledgments None. Statement of ethics Institutional review board approval was not required for this clinical image. Written informed consent was obtained. All procedures involving human participants adhered to institutional and national research committee ethical standards and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Conflict of interest statement The authors declare that they have no conflicts of interest. Funding source None. Author contributions DDL: Participated in conceptualization and writing. MRM: Participated in review and editing. MBM: Participated in supervision, review, and editing. Data availability No data were generated from this study.