Diagnosis: Proteus Syndrome (forme fruste)
Proteus Syndrome is a variable and complex disorder characterized by multifocal overgrowths affecting any tissue or structure of the body. Major clinical findings include hemihypertrophy, symmetric megalodactyly, subcutaneous masses (vascular, lymphatic, & lipomatous), epidermal nevi, and skull hyperostosis. As of 1999, roughly 120 cases had been reported in the literature. The phenotype is extremely variable, and can involve the pulmonary (cystic lung alterations), CNS (mental deficiency, seizures, brain malformation), renal, and other visceral malformations in addition to the aforementioned characteristics. The disease was named "Proteus Syndrome" in reference to the Greek God of the same name. Proteus was able to change his morphology at will in order to escape capture; the name reflects the variable constellation of findings in this syndrome. Since the original description of this syndrome in 1979, it has been determined that Joseph Merrick, the famed "Elephant Man", probably had Proteus syndrome, as opposed to Neurofibromatosis 1, as originally thought. The aetiology of this syndrome is unknown. Currently it is thought to be secondary to mosaicism of a post-zygotic early mutation. Treatment involves orthopaedic and plastic surgery intervention.
Our patient demonstrated asymmetrical features, macrodactyly and overgrowth of the hands and feet, numerous vascular and soft tissue malformations, and scoliosis. According to the scoring system developed by Hotamisligil in 1990 (with modification by Darmstadt & Lane in 1994), our patient satisfied only 10 out of the 13 or more points used to diagnose Proteus Syndrome. Therefore, we conclude that our patient most likely has a forme fruste of the syndrome.
Scoring System for diagnosis of Proteus Syndrome. Thirteen or more points are required to establish the diagnosis:
Macrodactyly and/or hemihypertrophy------------------- 5 points
Plantar and/or palmar cerebriform hyperplasia ----------4 points
Lipomatous and subcutaneous tumors------------------- 4 points
Verrucous epidermal nevi----------------------------------3 points
Macrocephaly or skull exostoses--------------------------2.5 points
Miscellaneous minor abnormalities-----------------------1 point
References:
Hotamisligil GS. Proteus syndrome and hamartoses with overgrowth. Dysmorph Clin Genet 1990; 4: 87-102.
Darmstadt GL, Lane AT. Proteus syndrome. Pediatric Dermatol 1994; 11:222-26.
Child FJ, Werring DJ, Du Vivier AWP. Proteus syndrome: diagnosis in adulthood. Br JDermatol 1998;139:132-136.
Plötz SG, Abeck D, Plötz W, Ring J. Proteus syndrome with widespread portwine stain naevus. Br J Dermatol 1998; 139: 1060-1063.
Ng SC, Khoo BS, Ho NK. Proteus syndrome. Journal of Paediatrics & Child Health 1997;33(3):264-266.
My thanks to Drs. Susan Schroeder and Susan Mallory for their assistance
in the preparation of this case.