Proteus syndrome: A rare case report.

Proteus syndrome (PS) is a rare hamartomatous disorder characterized by various cutaneous and subcutaneous lesions, including vascular malformations, lipomas, hyperpigmentation, and several types of nevi. Partial gigantism with limb or digital overgrowth is pathognomonic of PS. We report a rare case of PS in a 50-year-old man who presented with inferior wall myocardial infarction and was incidentally detected to have hypertrophy of index and middle fingers of both the hands.

Introduction

Proteus syndrome (PS) is a rare and sporadic disorder that causes postnatal overgrowth of tissues in a mosaic pattern.[1] It produces multifocal overgrowth of tissue derived from any of the three germinal layers. This causes a complex disorder with multisystem involvement and great clinical variability. The complications of PS include, progressive skeletal deformities, invasive lipomas, benign and malignant tumors, and deep venous thrombosis with pulmonary embolism.[1] We report a rare case of PS that presented with hypertrophy of index and middle finger without any other abnormalities or complications.

Case Report

A 50-year-old farmer presented to our emergency services with anginal pain. ECG revealed inferior wall myocardial infarction (MI). As patient presented in window period he was thrombolysed. Incidentally we noticed that he had enlarged index and middle fingers of both hands and thumb of right hand [Figure 1]. On probing patient revealed that it was present since childhood with onset around the age of 5 years and gradual progression over years to the present size. No similar tissue growth in other parts of the body and there was no one in the family with similar features. On examination there was hypertrophy of the involved fingers with limitation of movements. His systemic examination was otherwise normal.

Figure 1

Hypertrophy of index and middle finger of both the hand (a,b,c) and thumb of the right hand (c)

Laboratory investigations revealed normal renal and liver function tests. His X-ray of hands showed hyperostosis of involved fingers [Figure 2]. The chest X-ray and other skeletal survey were normal.

Figure 2

X - ray hands showing hyperostosis of both index and middle fingure (a,b) and thumb of right hand (b)

Discussion

Cohen and Hayden[2] first described this disease in 1979. The name Proteus comes from the Greek god ‘Proteus’ who had the ability to change his shape and was proposed by Wiedemann, et al.[3] in 1983.

The exact cause of PS remains unclear till date. Happle, et al.[4] in 1987 hypothesized that the syndrome might be due to somatic alteration of a gene leading to mosaic effects that would be lethal if the mutation were carried in nonmosaic fashion. The dysregulated tissue growth in mosaic pattern results in various phenotypic presentations and hence the clinical manifestations of PS are highly variable.[5]

The tissue overgrowth is usually absent or mild at birth and progressive in nature but usually appears to plateau after adolescence.[5] The disproportionate overgrowth of tissue is usually asymmetrical and involves the arms, legs, hands, feet, and digits. Characteristic manifestations include hyperostoses, often near epiphyses with associated impaired mobility and cerebriform connective tissue nevus seen most commonly on plantar surface. Other findings are lipomas, epidermal nevi and capillary vascular malformations [Table 1].

Table 1

Criteria for the diagnosis of proteus syndrome[6]

There is no specific molecular marker, or laboratory test, for the diagnosis of PS. The diagnosis is mainly based on history, clinical examination and imaging studies. The proposed criterion for the diagnosis of PS is shown in Table 1.

Because of its variable presentation, PS may be confused with other conditions. The two disorders most commonly confused with PS are Klippel-Trenaunay syndrome and hemihyperplasia/lipomatosis syndrome.[6] The others being those listed in Table 2. The important points in PS that help in the differential diagnosis are:

Table 2

Differential diagnosis of proteus syndrome[5]

Sporadic and progressive nature of tissue overgrowth

The absent or mild tissue growth at birth

Absence of bone tumor, enchondromas

Absence of specific gene mutations differentiates from neurofibromatosis

Absence of familial inheritance (postzygotic somatic mutation of genes)

There are no effective treatment modalities for PS. The patients should be followed up regularly for development of complications and their management. The management is also challenging because of progressive nature of tissue growth. Both benign and malignant tumors are associated with PS.[7] Two relatively common tumors include cystadenomas of the ovary and monomorphic adenomas of the parotid gland. The patients are also at risk of developing psychological and social problems.

Our patient presented with macrodactyly of index and middle finger of both the hands and thumb of right hand (one criteria of category B) and he met all the three general criteria. His skeletal survey was normal except for hyperostosis of index and middle finger and there were no associated complications except for the limitation of his affected finger movements. Although the patient did not satisfy the proposed criteria [Table 1], a literature search revealed that out of the 205 cases reported 90 satisfied the criteria highlighting the variability in clinical presentation in cases of PS.[6]

Our patient was managed as a case of inferior wall MI and is presently on anti-ischemic medications with no new complications.

In conclusion, PS is a very rare and highly variable, progressive tissue overgrowth disorder. Patients should be kept under regular follow-up for the development of complications and their management.