Proteus syndrome

Introduction: The term `Proteus syndrome' was first proposed by Wiedemann HR et al. in 1983 to describe a rare congenital hamartomatous malformation.[1] It is characterized by a wide range of deformities, including craniofacial, dermatological, and skeletal malformations. `Proteus,' the name of a Greek sea god who could change his shape at will, was the term used probably because of the polymorphic manifestations of the syndrome. Pulmonary involvement includes potentially lethal, rapidly progressive diffuse cystic emphysematous changes at an early age.[2]

Case Presentation: A 19-year-old white female was referred to our clinic for lung transplant evaluation. She was born from an uncomplicated gestation at 38 weeks. She was noted to have facial asymmetry, boney prominences over the eye-brows, and hypertrophy of the middle two fingers of her right hand (`partial gigantism') in early childhood. No diagnosis was entertained at that time; however, she underwent surgery on the boney prominences for cosmetic reasons, and on the fingers to improve function. Her height, weight and overall body growth have remained normal. She had sought medical attention at the age of 10 years for minimal breathlessness. She was diagnosed with asthma and prescribed inhaled beta-agonist without significant subjective improvement. No chest radiograph was obtained at that time. She was physically active, but noted her exercise performance to be less than that of her peers. She complained of gradually worsening dyspnea over at least 5 years. She admitted to a 2 pack year smoking history. Her medical history was otherwise unremarkable. She had an episode of pneumonia diagnosed 4 months prior to our evaluation. Chest radiograph obtained at that time revealed bibasilar infiltrates with cystic changes. On our evaluation, her lungs were clear, and rest of the physical exam was also unremarkable. Chest radiograph and CT scan revealed bilateral extensive reticular infiltrates with thickened interlobular septae, ground-glass attenuation, and cystic areas, larger in the bases, interspersed with dense fibrotic scarring. No lymphadenopathy was identified. Scoliosis of the thoracic vertebrae was noted. CT scan of abdomen was unremarkable except for 1.8 cm aneurysm at the splenic artery origin and scoliosis involving lumbar spine with fused multiple hemivertebrae. Pulmonary function tests revealed severe obstructive ventilatory defect with significant bronchodilator response, and severely reduced diffusing capacity that did not normalize after the correction for alveolar volume. The [FEV.sub.1] was 1.28 L (34% pred.), FVC 2.89 L (66% pred.), ratio [FEV.sub.1]/FVC 44%, and post-bronchodilator [FEV.sub.1] 1.62 L (increase of 27%). The TLC was 4.51 L 1% pred.), and DLCO 13.5 ml/min/mm Hg (56% pred.). Pulse oximetry revealed an [O.sub.2] saturation of 87% on room air, which increased to 94% with 2 L/min [O.sub.2] supplementation by nasal cannula. On 6-minute walk test, she walked 1120 feet with 6 L/min [O.sub.2] supplementation by nasal cannula, and her [O.sub.2] saturation at the end was 89%. Laboratory results revealed normal CBC, complete metabolic profile, and alpha-1-antitrypsin phenotype and level, c-ANCA and p-ANCA by immunofluorescence and enzyme immunoassay, antinuclear antibody, and rheumatoid factor were negative. EKG was normal. A clinical diagnosis of Proteus syndrome was made.

Discussion: The syndrome is diagnosed by a constellation of clinical features. It usually presents with multiple features during childhood, however it may not be diagnosed until adulthood. It has been diagnosed prenatally in a case by ultrasonographic findings of a cystic abdominal mass and malposition of the fingers.[3] Spinal canal compromise by an angiolipomatous mass or by vertebral hypertrophy causing progressive paraplegia has been described to occur in this syndrome.[4] The syndrome may be associated with or may predispose to neoplasms.[5] Pulmonary involvement in these patients is rare, and no definite therapy is known. A patient with pulmonary fibrocystic changes of Proteus syndrome has been treated with bilateral lung transplantation.[6]

Conclusion: The knowledge of pulmonary and other manifestations of this syndrome may help make the diagnosis. The management of each case has to be individualized, and lung transplantation may be a therapeutic option.

References

[1] Wiedemann HR, Burgio GR, Aldenhoff P, et al. The proteus syndrome. Eur J Pediatr 1983; 140:5-12

[2] Newman B, Urbach AH, Orenstein D, et al. Proteus syndrome: emphasis on the pulmonary manifestations. Pediatr Radiol 1994; 24:189-193

[3] Sigaudy S, Fredouille C, Gambarelli D, et al. Prenatal ultrasonographic findings in Proteus syndrome. Prenat Diagn 1998; 18:10911094

[4] Ring D, Snyder B. Spinal canal compromise in Proteus syndrome: case report and review of the literature. Am J Orthop 1997; 26:275-278

[5] Gordon PL, Wilroy RS, Lasater OE, et al. Neoplasms in Proteus syndrome. Am J Med Genet 1995; 57:74-78

[6] Armitage JM, Fricker FJ, Kurland G, et al. Pediatric lung transplantation: expanding indications, 1985 to 1993. J Heart Lung Transplant 1993; 12:S246-254

Bipin D. Sarodia, MD, S. B. Khatri, MD, R. J. Schilz, DO, PhD--Department of Pulmonary and Critical Care Medicine, Cleveland Clinic, Cleveland, OH

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