Proteus Syndrome: Case Report and Updated Literature Review

Abstract

Proteus syndrome (PS) is an exceptionally uncommon genetic disorder that has been documented in only approximately 250 cases in the literature spanning the past four decades. It is characterized by a disproportionate, asymmetric overgrowth of all types of tissues, provoked by a somatic activating mutation in serine/threonine protein kinase 1. We report a case of PS in a two-year-old female patient with the following clinical features: unilateral overgrowth of connective tissue in the right buttock and right foot, where multiple surgeries were performed to achieve a desirable aesthetic outcome and ensure psychological comfort of the young patient. The insights provided by this case underscore the pivotal role of obtaining pleasing aesthetic outcomes in the surgical management of untreatable genetic disorders, with the aim of nurturing psychological contentment in affected children.

Keywords

case report - genetic disorders - Proteus syndrome - pediatric plastic surgery

Authors' Contributions

M.K.K.C. was responsible for Conceptualization (Equal), Data curation (Lead), Formal analysis (Lead), Investigation (Lead), Resources (Equal), Writing—original draft (Lead)

M.K. was responsible for Conceptualization (Equal), Data curation (Supporting), Investigation (Supporting), Visualization (Lead), Writing—review and editing (Equal)

A.C. was responsible for Data curation (Supporting), Formal analysis (Supporting), Funding acquisition (Lead), Investigation (Supporting), Project administration (Lead), Resources (Lead), Supervision (Lead), Validation (Lead), Writing—review and editing (Supporting)

Ethical Approval

Approval was obtained from the ethics committee of Regional Medical Chamber in Kraków. This study adheres to the tenets of the Declaration of Helsinki.

Patient Consent

The patients provided written informed consent for the publication and the use of their images.

Publication History

Received: 18 October 2023

Accepted: 03 April 2024

Accepted Manuscript online:
05 April 2024

Article published online:
14 June 2024

• References

• 1 Cohen Jr MM. Proteus syndrome review: molecular, clinical, and pathologic features. Clin Genet 2014; 85 (02) 111-119
• 2 Lindhurst MJ, Sapp JC, Teer JK. et al. A mosaic activating mutation in AKT1 associated with the Proteus syndrome. N Engl J Med 2011; 365 (07) 611-619
• 3 Cohen Jr MM, Hayden PW. A newly recognized hamartomatous syndrome. Birth Defects Orig Artic Ser 1979; 15 (5B): 291-296
• 4 Amer N, Al Helal J, Al Hajji M. et al. Proteus syndrome, a rare case with an unusual presentation: case report. Int J Surg Case Rep 2020; 72: 339-342
• 5 Munhoz L, Arita ES, Nishimura DA, Watanabe PCA. Maxillofacial manifestations of Proteus syndrome: a systematic review with a case report. Oral Radiol 2021; 37 (01) 2-12
• 6 Furquim I, Honjo R, Bae R. et al. Proteus syndrome: report of a case with recurrent abdominal lipomatosis. J Pediatr Surg 2009; 44 (04) E1-E3
• 7 Ou M, Sun Z, Zhu P, Sun G, Dai Y. Proteus syndrome: a case report and review of the literature. Mol Clin Oncol 2017; 6 (03) 381-383
• 8 Buser A, Lindhurst MJ, Kondolf HC. et al. Allelic heterogeneity of Proteus syndrome. Cold Spring Harb Mol Case Stud 2020; 6 (03) a005181
• 9 Duarte Santos C, Lizardo Grácio R, Costa Pires T. et al. Proteus syndrome: a rare case in an adult ward. Eur J Case Rep Intern Med 2021; 8 (04) 002554
• 10 Rocha RCC, Estrella MPS, Amaral DMD, Barbosa AM, Abreu MAMM. Proteus syndrome. . An Bras Dermatol 2017; 92 (05) 717-720
• 11 Weibel L, Theiler M, Gnannt R. et al. Reduction of disease burden with early sirolimus treatment in a child with Proteus syndrome. JAMA Dermatol 2021; 157 (12) 1514-1516
• 12 Ours CA, Sapp JC, Hodges MB, de Moya AJ, Biesecker LG. Case report: five-year experience of AKT inhibition with miransertib (MK-7075) in an individual with Proteus syndrome. Cold Spring Harb Mol Case Stud 2021; 7 (06) a006134
• 13 Leoni C, Gullo G, Resta N. et al. First evidence of a therapeutic effect of miransertib in a teenager with Proteus syndrome and ovarian carcinoma. Am J Med Genet A 2019; 179 (07) 1319-1324
• 14 Lindhurst MJ, Yourick MR, Yu Y, Savage RE, Ferrari D, Biesecker LG. Repression of AKT signaling by ARQ 092 in cells and tissues from patients with Proteus syndrome. Sci Rep 2015; 5: 17162
• 15 Crenshaw MM, Goerlich CG, Ivey LE. et al. Orthopaedic management of leg-length discrepancy in Proteus syndrome: a case series. J Pediatr Orthop 2018; 38 (03) e138-e144
• 16 Modlin EW, Slavotinek AM, Darling TN. et al. Late-onset Proteus syndrome with cerebriform connective tissue nevus and subsequent development of intraductal papilloma. Am J Med Genet A 2022; 188 (09) 2766-2771
• 17 Keppler-Noreuil KM, Sapp JC, Lindhurst MJ. et al. Pharmacodynamic study of miransertib in individuals with Proteus syndrome. Am J Hum Genet 2019; 104 (03) 484-491
• 18 Popescu MD, Burnei G, Draghici L, Draghici I. Proteus syndrome: a difficult diagnosis and management plan. J Med Life 2014; 7 (04) 563-566
• 19 He M, Zhao W. Proteus syndrome of the foot: a case report and literature review. Exp Ther Med 2020; 20 (03) 2716-2720
• 20 Biesecker LG, Happle R, Mulliken JB. et al. Proteus syndrome: diagnostic criteria, differential diagnosis, and patient evaluation. Am J Med Genet 1999; 84 (05) 389-395
• 21 Biesecker L. The challenges of Proteus syndrome: diagnosis and management. Eur J Hum Genet 2006; 14 (11) 1151-1157
• 22 Zhou X, Hampel H, Thiele H. et al. Association of germline mutation in the PTEN tumour suppressor gene and Proteus and Proteus-like syndromes. Lancet 2001; 358 (9277) 210-211
• 23 Cohen Jr MM, Turner JT, Biesecker LG. Proteus syndrome: misdiagnosis with PTEN mutations. Am J Med Genet A 2003; 122A [phone]
• 24 Sapp JC, Buser A, Burton-Akright J, Keppler-Noreuil KM, Biesecker LG. A dyadic genotype-phenotype approach to diagnostic criteria for Proteus syndrome. Am J Med Genet C Semin Med Genet 2019; 181 (04) 565-570
• 25 Biesecker LG, Sapp JC. Proteus syndrome. In: Adam MP, Mirzaa GM, Pagon RA. , et al, eds. GeneReviews®. Seattle (WA):: University of Washington; ; 1993–2023. 2012. . Updated May 25, 2023.
• 26 Sapp JC, Turner JT, van de Kamp JM, van Dijk FS, Lowry RB, Biesecker LG. Newly delineated syndrome of congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome) in seven patients. Am J Med Genet A 2007; 143A (24) 2944-2958
• 27 Robert J, Marchand A, Mazereeuw-Hautier J. et al; Groupe de Recherche de la Société Française de Dermatologie Pédiatrique. Quality of life of children with capillary malformations of the lower limbs: Evolution and associated factors. Data from the French national paediatric cohort, CONAPE. Ann Dermatol Venereol 2022; 149 (04) 271-275
• 28 Harvey JA, Nguyen H, Anderson KR. et al. Pain, psychiatric comorbidities, and psychosocial stressors associated with Klippel-Trenaunay syndrome. J Am Acad Dermatol 2018; 79 (05) 899-903