Proteus Syndrome
Radiology Cases in Pediatric Emergency Medicine
Volume 7, Case 4
Craig T. Nakamura, MD
Kapiolani Medical Center For Women And Children
University of Hawaii John A. Burns School of Medicine
     This is a 16 year old female who presents to the 
emergency department with a two day history of 
coughing, productive for small amounts of thin, yellow 
mucous.  She also has two episodes of mild 
hemoptysis each day (5 milliliters per episode).  She 
had a low grade fever and clear rhinorrhea 5 days ago, 
which has resolved.  She denies shortness of breath, 
wheezing, chest pain, headaches, malaise, chills, 
symptoms of reflux, weight loss, rashes, and joint 
pains.  However, she does become dyspneic with 
prolonged activity.  There are several family members 
with rhinorrhea and low grade fevers.  There is no 
history of recent travel.
     The patient has a history remarkable for lung cysts 
of unknown etiology.  At the age of 10, she developed 
similar symptoms.  A chest radiograph revealed 
bilateral cystic changes thought to be secondary to 
bronchiectasis.  A follow-up film several months later 
reportedly showed a progression of the right middle 
lobe cyst.  Bronchoscopy was normal and a TB skin 
test was negative.  The cyst was surgically excised.  
Pathology revealed atrophic lung parenchyma lining the 
cyst and chronic nonspecific inflammation.  No atypical 
cells were present.
     Her birth history is unremarkable.  A chest 
radiograph from infancy was normal.  Her past medical 
history is significant for left hand hemihypertrophy 
which was noted shortly after birth.  At 5 years of age, 
metal plates were placed in her left hand to retard the 
hemihypertrophy.  As mentioned, a chest radiograph at 
10 years of age revealed cystic lung disease and she 
underwent a resection of a right middle lobe cyst.  Her 
family history is unremarkable for pulmonary, 
connective tissue, or genetic disorders.
     Exam:  T36.3, P 96, RR 24, BP 110/72, oxygen 
saturation 91%-95% in room air.  Weight 39.7 kg (<5th 
percentile).  Height 164 cm (70%ile).
     She is a thin, well developed alert female in no 
distress.  Skin:  No rashes, lesions, thickened skin, or 
varicosities.   Head:  Normocephalic.  EENT:  Normal.  
Neck:  No elongation or adenopathy.  Chest: 
Symmetrical with normal anteroposterior diameter.  No 
retractions.  No scoliosis or kyphosis noted.  Mild 
pectus excavatum is present.  No tympany to 
percussion.  A surgical scar is noted.  Lungs:  Mildly 
decreased breath sounds.  No rhonchi, rales, or 
wheeze.  No prolongation of the expiratory phase.  
Heart:  Regular rate and rhythm.  No murmur.  Normal 
S2.  No gallop.  Abdomen:  Benign.  No organomegaly.  
Extremities:  Enlarged left hand with long fingers.  
There is also joint enlargement involving her left hand.  
No other hemihypertrophy noted.
     Arterial blood gas:  pH 7.39, pCO2 40, pO2 55, 
bicarbonate 24.

Review her radiographs:

Review her CXR at an early age.

Review a later CXR.

Review her current CXR.

Review her hand radiographs.

     The patient was hospitalized for further evaluation of 
her cystic lung disease as well as treatment of her 
hypoxemia.  A genetics evaluation was obtained upon 

     The name, Proteus syndrome, was coined by 
Wiedemann in 1983 after the Greek sea God, Proteus 
(1).   As the son of Poseidon, Proteus possessed the 
ability to transform himself into any shape to avoid 
prophesying the futures of the mortals who hounded 
him.  Like the Greek God, this syndrome manifests 
itself in many ways.  The most famous patient afflicted 
with Proteus syndrome was Joseph Merrick, better 
known as the "Elephant Man" (2).
     Proteus syndrome is an uncommon clinical entity 
characterized by abnormalities in growth (asymmetric 
overgrowth, increased stature, macrodactyly, soft 
tissue hypertrophy, elongated neck, macrocephaly), 
skin (plantar and palmar skin thickening, epidermal 
nevi, lipomas, lymphangiomas, hemangiomas, cafe au 
lait spots, varicosities, dermal hypoplasia), 
musculoskeletal (hemihypertrophy, bony prominences, 
ankle ankylosis, craniosynostosis, mandibular 
prognathia, scoliosis, pectus excavatum, thinning of the 
cortical layer of long bones), eye (ptosis, strabismus, 
nystagmus, myopia, colobomas, cataracts, epibulbar 
dermoids, blue sclera), central nervous system 
(seizures, mental retardation), venous (varicosities, 
hemorrhoids, dilated superior mesenteric and 
pulmonary veins) and as in this patient, cystic lung 
disease (3-7).
     Patients afflicted with Proteus syndrome frequently 
appear normal at birth.  Features begin to appear 
during the first year of life with subsequent progression.  
The etiology of Proteus syndrome remains unknown.  
The majority of patients have a normal chromosomal 
complement.  However, it has been suggested that 
there may be a mosaic somatic mutation affecting the 
regulation of tissue growth factors, leading to the 
associated polymorphic characteristics of this disease 
(8-12).  We will focus on the pulmonary disease and 
chest radiographic findings associated with Proteus 
     The most striking radiographic finding are cystic 
lung lesions (1,2,5,13).  These cysts can be quite large 
and may be distributed unilaterally or bilaterally.  There 
is no preference for any particular lobe to be involved.  
Another reported finding is the prominence of 
pulmonary markings with obstructive lung parenchymal 
changes (4).  The chest radiograph may also reveal 
dilated pulmonary veins, scoliosis (2), kyphosis (4), 
dysplastic or enlarged thoracic vertebrae (14), rib 
hypertrophy (12,15), and soft tissue masses (16). 
     The differential of cystic lung disease includes 
bronchopulmonary dysplasia (17), bronchogenic cysts 
(18), Marfan syndrome (19,20), neurofibromatosis (21), 
tuberous sclerosis (22), bronchiectasis, 
pneumatoceles, pneumoconiosis, alpha-1-antitrypsin 
deficiency (23), cystic adenomatoid malformation (24), 
histiocytosis X (25), and sarcoidosis (26).
     The morbidity and mortality risk of pulmonary cysts 
in Proteus syndrome is unknown.  Treatment generally 
focuses on minimizing further lung damage and 
avoiding infection of the cysts to prevent respiratory 
compromise.  If these attempts prove to be 
unsuccessful, lung transplantation may be an option 
(5,27).  In the future, further efforts may be made to 
further delineate the exact etiology of this syndrome, 
which may suggest alternate forms of therapy.

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J, Kaufmann HG, Schirg E.  The proteus syndrome.  
European Journal of Pediatrics 1983;140:5-12.
     2.  Tibbles JAR, Cohen MM Jr.   The proteus 
syndrome: The elephant man diagnosed.  British 
Medical Journal 1986;293:683-685.
     3.  Proteus Syndrome.  In:  Jones KL.  Smith's 
Recognizable Patterns of Human Malformation. 4th 
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     4.  Barona-Mazuera M, Hidalgo-Galvan LR, 
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resembling the Proteus syndrome with a chromosome 
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of bone and hemangiomas and lipomas of soft tissue 
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a neonate with Marfan syndrome.  Pediatric Radiology 
     21.  Webb WR, Goodman PC.  Fibrosing alveolitis 
in patients with neurofibromatosis.  Radiology 
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tuberous sclerosis.  Report of three patients and a 
review of the literature.  Quart J Med 1971;40:115-125.
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     24.  Nokes SR, Pierce WB.  Radiological case of 
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lung transplantation.  Journal of Thoracic and 
Cardiovascular Surgery 1995;109(1): 60-65.

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Web Page Author:
Loren Yamamoto, MD, MPH
Professor of Pediatrics
University of Hawaii John A. Burns School of Medicine