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At a glance

A rare congenital hamartomatous disorder characterized by multiple, diverse, somatic manifestations: partial bilateral gigantism of hands and feet, nevi, hemihypertrophy, subcutaneous tumors, macrocephaly with cranial hyperostoses.

Synonyms

Elattoproteus Syndrome; Wiedemann Syndrome; Partial Gigantism of Hands and Feet Syndrome; Nevi Hemihypertrophy Macrocephaly Syndrome; Encephalocraniocutaneous Lipomatosis Syndrome; Hamartomas Disorder, Multifarious Mesodermal Malformation, Plurifocal Overgrowth.

History

It is named after the Greek god Proteus, “the polymorphous,” who could change his shape at will to avoid capture. Proteus lived on the Island of Pharos, close to the mouth of the Nile or in the caves of the island of Karpathos, between Crete and Rhodos. It was described by Hans-Rudolf Wiedemann, a German pediatrician, in 1983. Joseph Merrick, known as the “elephant man” is now, in retrospect, believed to have been affected by Proteus Syndrome.

Incidence

Internationally, it is estimated that approximately 200 individuals are affected with this medical condition. The prevalence is believed to be less than 1 per 1,000,000 live births. There is no predilection for any race and sex. All cases are sporadic. At least, some of the abnormalities are present at birth, or they appear within the first year of life. This medical condition usually progresses until puberty.

Genetic inheritance

Sporadic and nonfamilial.

Pathophysiology

Proteus Syndrome is associated with mosaicism for a somatic activating mutation in the AKT1 gene on chromosome 14q32.3. Up-regulation of AKT1 phosphorylation as a result of a heterozygous mutation in AKT1 occurs in some tissues of patients with the Proteus Syndrome and suggests that constitutive activation of the protein underlies the overgrowth and tumor susceptibility in these patients.

Proteus Syndrome: Digital gigantism in an infant with Proteus Syndrome.

Diagnosis

The diagnostic criteria of Proteus Syndrome include regional generalized tissue hyperplasia (such as digital gigantism, macrocephaly, hemihypertrophy), skin lesions (eg, hypo- or hyperpigmented, thickened skin creases), and mesodermal hamartomas (such as lipoma, lymphangioma, hemangioma, exostosis, or fibroma). There is unique marked hypertrophy of the skin of the soles—”Moccasin Sole”—with light microscopic findings of elongation of the cytoplasm of basal cells. Histologic examination of subcutaneous masses has identified a variety of lipomatous, hamartomatous, and angiomatous tumors.

Clinical aspects

The disease appears soon after birth and progresses at a variable rate leading to gross deformity in later childhood. Some patients are born with large, complex, mixed vascular malformations. Overgrowth, usually digital, is noted during infancy. In childhood, patients may also develop linear epidermal nevi. The skeletal system is mainly affected with hemihypertrophy, macrodactyly, scoliosis, and exostoses over the skull. Intelligence is usually normal. Spinal compromise may develop in Proteus Syndrome from vertebral anomalies (eg, angular kyphoscoliosis) ...

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