English Version
D. Sethi

Proteus syndrome

Proteus syndrome

Schlüsselwörter Proteus syndrome; ICD 10: Q87.3; Wiedemann syndrome, Elephant man disease
Keywords Proteus syndrome; ICD 10: Q87.3; Wiedemann syndrome, Elephant man disease
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Proteus syndrome (PS) is a rare hamartomata disorder in which there is asymmetric overgrowth of multiple body tissues causing severe disfigurement. Its global incidence is estimated to be less than 1 in a million. The syndrome, first described by Cohen and Hayden in 1979, was named by Wiedemann in 1983 after the Greek sea god ‘Proteus’ who had the ability to transform into any shape.

It has been hypothesized recently that PS is caused by post-zygotic mosaic mutation of somatic genes. Researchers have recently identified mutation of the AKT1 gene (14q32.33) as the cause of unregulated growth of cells involving the three germ layers.  The p.Glu17Lys mutation triggers constitutive activation of the AKT1 kinase, which results in signal transduction from tyrosine kinase receptor, in turn causing accelerated growth of cells with inhibition of apoptosis.   This mutation is not inherited and is lethal in its non-mosaic variant. The severity of PS depends on how early the mutation has occurred during embryonic development and in which cell line. Only the progeny cells from the mutated cell display the disease hallmark i.e. unregulated growth, thus the individual grows with a combination of normal and mutated cells.

The syndrome is sporadic, non-familial and has a progressive course. The affected individual is born without any deformity with the abnormal body growth becoming apparent only in the first few years after birth.  Accelerated overgrowth is seen during childhood and tends to plateau after adolescence as the growth plate activity slows down.

The most common and striking feature of PS  is disproportionate skeletal overgrowth causing hemi hypertrophy, asymmetric limbs with disproportionate length, macrodactyly and vertebral anomalies. Other features include asymmetric muscle development, lipomas or lipoatrophy, hyper-pigmented skin lesions, epidermal nevi, cerebriform connective tissue nevi, vascular malformations, tumours of ovary or parotid glands and visceral involvement such as cystic lung disease.

As there is massive heterogeneity in the clinical presentation and the severity of clinical features is highly varied, accurate diagnosis of PS can be challenging. The differential diagnosis of PS  includes several disorders such as hamartomatous tumour syndrome, neurofibromatosis type 1, hemihyperplasia, multiple lipamatosis, Klippel Trenaunay syndrome, Maffucci syndrome or CLOVE syndrome (congenital lipomatous overgrowth, vascular anomalies and epidermal nevi).

For establishing diagnosis of PS, the criteria laid down by the National Institute of Health are  followed (1998). These require the presence of three general (mandatory) features including mosaic distribution of lesions, progressive course and sporadic occurrence together with identifying some of the specific clinical features. The clinical diagnosis can be supplemented by genetic analysis and identifying AKT1 gene mutation. In addition, genetic analysis can be a useful tool in patients in whom the clinical features are mild and the symptoms are ambiguous. For genetic testing, DNA from the biopsy samples from affected tissues is analysed; typically, a punch biopsy of an affected skin area is used.


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