Proteus syndrome

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S[2]

Synonyms and Keywords: PS

Overview

Proteus syndrome is an exceedingly rare disorder which falls under the category of hamartomatous disorder. Proteus syndrome is a very complex disorder which involves multiple organ systems in the body. In The United States of America in order to categorise a condition is a rare disease it should affect fewer than 200,000 people. Rare diseases also called as orphan diseases. Orphan Drug Act was passed on 1983 by congress for the rare diseases. Today an average of 25-30 million americans have been reported with rare diseases. The number of people with individual rare disease may be less but overall the number of people with rare diseases are large in number.

Historical Perspective

Discovery

  • Proteus syndrome was first discovered by Frederick Treves, a British surgeon, in 1884.[1]
  • Frederick Treves showed the proteus syndrome on Joseph Merrick, who used to be called as the famous Elephant Man, to the Pathological Society of London.[2][3]

Classification

Pathophysiology

Causes

Differentiating Proteus syndrome from other Diseases

Proteus syndrome must be differentiated from the following rare disorders:[18][19][20][21][22][23]

Epidemiology and Demographics

Incidence

  • The incidence of proteus syndrome is approximately 1 per 1,000,000-1:10,000,000 individuals worldwide.[24][25]
  • There are few than 100 cases of proteus syndrome have been reported worldwide.

Race

  • There is no racial predilection to proteus syndrome.[26]

Gender

  • Males are more commonly affected by proteus syndrome than females.

Risk Factors

Screening

  • There is insufficient evidence to recommend routine screening for proteus syndrome.

Natural History, Complications, and Prognosis

Natural History

Complications

Prognosis

  • Prognosis is generally excellent in mildly affected children with proteus syndrome.[35]
  • Depending on the location of the gene and the degree of the overgrowth at the time of diagnosis, the prognosis may vary.[36]
  • Survival rate of patients with proteus syndrome is approximately ranges from nine months to 29 years based on the severity of the condition.[37]

Diagnosis

Diagnostic study of choice

Diagnostic criteria of Proteus syndrome includes the following:

  • According to the National Institutes of Health in 1998, diagnosis of the proteus syndrome requires the following:[42]
    • Positive all general characteristics and one feature of category A or two features of category of B or three features of category C
General criteria

(All are Required)[43][44]

Specific criteria

Category A[45][46]

Specific criteria

Category B[47][48]

Specific criteria

Category C[49][50]

(All the three are reuired)

  • Asymmetric or disproportionate overgrowth

of one or more of the following:

limbs, digits, cranium, vertebrae, spleen

external auditory meatus, and or thymus

  • Specific tumors with onset before the second decade:

Bilateral ovarian cystadenomas or parotid monomorphic adenoma

  • Following a progressive course

History and Symptoms

History

Common Symptoms[54][55]

Physical Examination

Skin

Back

HEENT

Extremities

Proteus syndrome overgrowth
Proteus syndrome- Note the generalized overgrowth, upper and lower limb length discrepancy, localized limb distortion of the left knee (A), postural flexion deformity of the left knee (B), and mild dorsal scoliotic deformity (C). Case courtesy by Tamer Ahmed EL-Sobky Et Al[63]
X-ray in Proteus Syndrome- Asymmetric and disproportionate overgrowth of right hand fingers with macrodactyly. Case courtesy -Suresh Kumar Angurana Et Al[64]
Proteus syndrome
(A) Right hemihypertrophy, (B) subcutaneous tumors and lipoma, (C) macrodactyly of the third and fourth digits of the right hand, and (D) macrodactyly of nearly all the toes. Pic courtesy by Zuleyha Sik Sarman Et Al [68]

Laboratory Findings

Electrocardiogram

  • There are no ECG findings associated with proteus syndrome.

X-Ray Findings

Ultrasound

CT-Scan Findings

MRI Findings

Temporal lobe cavernoma
Magnetic resonance imaging of the case, showing temporal lobe cavernoma, Pic courtesy by Zuleyha Sik Sarman Et Al [83]

Treatment

Medical Therapy

  • The majority of cases of proteus syndrome require orthopedic management and it is challenging.

Surgery

  • Surgery is the mainstay of treatment for proteus syndrome patients.

Epiphysiostasis and Epiphysiodesis

  • Epiphysiostasis is a form of surgery which helps in reduces projected limb length which is a form of temporary growth arrest.[84][85][86]
  • Epiphysiostasis is done in children with proteus syndrome who are many years away from puberty.
  • Epiphysiostasis is only considered and done in overgrowth limb not the normal limb which is short.
  • Epiphysiodesis is usally considered when the patient enters into teens.
  • The advantage of doing epiphysiostasis and epiphysiodesis the patients can be ambulatory after the surgery very fast and it reduces the risk of formation of thrombosis.[87]

Amputation

Patellectomy

Spinal Bracing

  • Spinal bracing considered in patients with scoliosis in proteus syndrome due to life-threatening consequences.[90]
  • Spinal bracing should be considered when the patients with proteus syndrome when spinal curve as small as 10°.

Joint Replacement

Foot Care

Primary Prevention

Secondary Prevention

References

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  58. Biesecker L (November 2006). "The challenges of Proteus syndrome: diagnosis and management". Eur. J. Hum. Genet. 14 (11): 1151–7. doi:10.1038/sj.ejhg.5201638. PMID 16883308.
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