Proteus syndrome is a rare genetic disorder distinguished by an overgrowth of many different tissues in the body in a mosaic pattern. The skin, the musculoskeletal system, the central nervous system, and adipose tissues are affected the most, producing profound disfigurement and life-threatening complications. The diagnosis is made through a combination of clinical criteria and positive genetic studies for AKT1 gene mutations.
Although Proteus syndrome is rarely encountered in clinical practice, several distinct signs are recognized in the affected population. Tissue overgrowth is, by far, the most important feature of this disorder and the skeletal system seems to be most severely affected      . After an apparently normal birth, first signs usually appear in late infancy and early childhood (6-18 months of age), but a delayed presentation up to puberty has been encountered  . Skeletal changes affect the limbs in most cases in an evidently disproportionate, asymmetric, and often severe and rapidly progressing fashion (leg length discrepancy of up to 20 centimeters has been reported)  . The connective tissues and fat are also affected by this phenomenon, but atrophy of the adipose tissue can be simultaneously present in some patients   . Furthermore, studies have reported cases with overgrowth of different organs, including the thymus, the gastrointestinal tract, the spleen, and the liver  . Vascular malformations involving, the arterial, venous, and/or lymphatic vessels are very frequent and predispose to life-threatening thromboembolic events   . Apart from tissue overgrowth, the formation of cutaneous lesions, such as linear verrucous epidermal nevi and cerebriform connective tissue nevi (CCTN) are hallmarks of Proteus syndrome    . Other notable findings seen in Proteus syndrome are    :
- Facial deformities - Flattening of malar bones, an open mouth at rest, and down-slanting palpebral fissures are seen in a small proportion of patients and intellectual disability may often accompany facial changes   .
- Neoplasias - Parotid gland adenomas, ovarian cystadenomas, and sometimes meningiomas are tumor types that are strongly correlated with Proteus syndrome.
- Bullous and cystic lung disease  .
Unfortunately, Proteus syndrome is severely debilitating during childhood and adolescence and up to 25% of patients are at risk of not surviving past the beginning of the third decade of life . For this reason, an early diagnosis is essential. To recognize Proteus syndrome, it is first necessary to establish prerequisite criteria - a mosaic pattern of lesions, the absence of a familial component, and a rapidly progressive course of symptoms   . During the clinical assessment, use of diagnostic criteria that have been revised in the previous decade should be sufficient to solidify clinical suspicion   .
- Category A signs - Cerebriform connective tissue nevi.
- Category B signs - Linear verrucous epidermal nevus; Presence of disproportionate and asymmetric overgrowth of the limbs, hyperostosis of the skull or of the external auditory canal, visceral overgrowth, or megaspondylodysplasia; and the presence of either bilateral ovarian cystadenomas or parotid adenomas.
- Category C signs - Abnormal adipose tissue formation (either lipoatrophy or overgrowth), vascular changes, facial deformities, and typical lung disease.
The diagnosis is made when either Category A is fulfilled, when two signs from category B exist, or if three signs from category C are observed   . In addition to clinical findings, the revelation of specific mutations involving the AKT1 gene has allowed mutational analysis to be performed in this population ; thus genetic testing can be employed as a definitive diagnostic method   .
There is no cure or specific treatment for Proteus syndrome and treatment involves medical and surgical management of symptoms. [texaschildrens.org]
What is the treatment for Proteus syndrome? There is no specific treatment for Proteus syndrome. The condition should be managed by identifying early any serious medical problems and providing prophylactic and symptomatic treatment. [dermnetnz.org]
The ideal treatment would have to begin when the patients were very young and maintained until adulthood, if not longer. [genome.gov]
even with aggressive treatment (4). [spandidos-publications.com]
Treatment generally focuses on minimizing and managing symptoms. [healthline.com]
Prognosis Prognosis varies depending on the severity of complications. The documents contained in this web site are presented for information purposes only. [orpha.net]
Prognosis of affected patients may be complicated by premature death, mostly due to pulmonary embolism and respiratory failure. [ncbi.nlm.nih.gov]
This disorder is thought to be caused by a somatic gene mutation, but the exact etiology is unknown. Commonly involved tissues include connective tissue, bone, skin and the central nervous system. [ncbi.nlm.nih.gov]
Although AKT1 mutations have been identified as a cause of Proteus syndrome, the precise pathogenesis and etiology of this syndrome require further investigation. [spandidos-publications.com]
[…] fat of the extremities vascular malformations: capillary, venous or lymphatic Less common findings include 1: bilateral ovarian cystadenomas parotid monomorphic adenoma abnormal facial features, e.g. dolichocephaly, low nasal bridge, anteverted nares Etiology [radiopaedia.org]
Keywords: Aftercare, Case Report, Human, Infant, Male, Proteus Syndrome, complications,epidemiology,genetics,pathology,surgery, How to cite this article: Alavi S, Chakrapani A, Kher A, Bharucha B A. The Proteus syndrome. [jpgmonline.com]
Summary Epidemiology Approximately 120 cases of PS have been reported to date. The prevalence is estimated to be less than 1/1,000,000 live births. Clinical description Neonates usually appear normal at birth. [orpha.net]
Epidemiology Frequency International Proteus syndrome is believed to be exceedingly rare, with less than 100 confirmed affected individuals reported worldwide.  This suggests that prevalence is less than 1 case per 1,000,000 live births. [emedicine.medscape.com]
Pathophysiology Proteus Syndrome is associated with mosaicism for a somatic activating mutation in the AKT1 gene on chromosome 14q32.3. [accessanesthesiology.mhmedical.com]
We conclude that the predisposition to thrombosis is likely to be multifaceted with risk factors including vascular malformations, immobility, surgery, additional prothrombotic factors, and possible pathophysiologic effects of the somatic AKT1 mutation [ncbi.nlm.nih.gov]
The principal investigator is Leslie G Biesecker, M.D., Chief of the Medical Genomics and Metabolic Genetics Branch at the National Human Genome Research Institute (NHGRI) who discovered the important role AKT plays in the pathophysiology of Proteus syndrome [raredr.com]
Pathophysiology A study by Lindhurst et al demonstrated that a somatic mutation in the AKT1 gene is causative for Proteus syndrome. [emedicine.medscape.com]
It doesn't run in families, and there is nothing parents can do to prevent it. What Are the Symptoms of Proteus Syndrome? Proteus syndrome symptoms don’t appear right away. [webmd.com]
Management to prevent and monitor for blood clots is needed. Imaging. Imaging studies (x-rays) are often important to assess and monitor areas of overgrowth. No one type of imaging is best for everyone with Proteus syndrome. [texaschildrens.org]
Doctors may also suggest surgically removing growth plates in the bone to prevent excessive growth. Proteus syndrome can cause numerous complications. Some can be life-threatening. Your child may develop large masses. [healthline.com]
Epiphysiodesis (removal or ablation of growth plates in bones) may be especially useful to prevent or treat the skeletal overgrowth of Proteus syndrome. [rarediseases.org]
Tea tree oil : Tea tree oil is purported to have antiseptic properties, and has been used traditionally to prevent and treat infections. [livingnaturally.com]
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- Cohen MM Jr. Proteus syndrome review: molecular, clinical, and pathologic features. Clin Genet. 2014 Feb;85(2):111-119.
- Alves C, Acosta AX, Toralles MBP. Proteus syndrome: Clinical diagnosis of a series of cases. Indian J Endocrinol Metab. 2013;17(6):1053-1056.
- Biesecker L. The challenges of Proteus syndrome: diagnosis and management. Eur J Hum Genet. 2006;14(11):1151-1157.
- Talari K, Subbanna PKA, Amalnath D, Suri SDK. Proteus syndrome: A rare case report. Indian J Hum Genet. 2012;18(3):356-358.
- Sapp JC, Hu L, Zhao J, et al. Quantifying survival in patients with Proteus syndrome. Genet Med. 2017 Jun 29.
- 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(7):611-619.