Proteus syndrome (PS) is a rare pathology characterized by mosaic and progressive hypertrophies, that can affect any organ or tissue of the body. A genetic mutation in the embryo is at the origin of the disease. Bones, fat, skin and connective tissue are the tissues most typically involved. The extent and severity of the abnormalities vary, giving different clinical presentations. The authors report two cases in two boys aged three and eight years respectively. In both, segmental and organ growth abnormalities, skin abnormalities and lipomas were present. The youngest patient was admitted for the management of severe malnutrition. He presented a major excrescence in the gluteal region, which required surgical management mainly because of its functional impact. In the second patient who was hospitalized following a viral meningoencephalitis, important vascular abnormalities were demonstrated, particularly at the cerebral and abdominal level. The clinical presentation was more severe in the latter, with the installation of an extended coma and a comitial state. PS is a pathology which could be incapacitating. It exposes to a high risk of benign tumours and deep venous thrombosis. The variability of abnormalities and the risks incurred required multidisciplinary management.
Proteus syndrome (PS) is a rare pathology characterised by a mosaic progressive hypertrophy which could affect any organ or any tissue of the body. An embryonic genetic mutation could be the causes. Bones, fat, skin, and conjunctive tissue are more typically involved. Extent and severity of the disease vary from one individual to another, giving different clinical presentations. The authors report two cases of two boys aged respectively 3 and 8 years.
A three years old boy, the last of 6 children, without any known family history of congenital disease, was admitted with severe malnutrition (z-score P/T < −3 ET) complicated by anemia. The child was cachectic with tiny limbs and macrocephaly. The examination shows a right side body hemi-hypertrophy with asymmetrical ears (
The plantar surface of the right foot was cribriform. An epidermal naevus was seen at the right cervical region and homolateral ear (
There was an extra growth at the gluteal region and the right thigh affecting walking and some postures like sitting (
CT scan of the growth shows a huge heterogeneous subcutaneous soft tissue mass poorly circumscribed measuring 196 × 55 mm, with an important fatty tissue poorly enhanced by injected contrast, attached to the gluteal muscles. There was right ileo-femoral dysplasia with ascending of the femoral head. Abdomino-pelvic CT scan show a big right kidney, sub-renal lymphangioma and right hydrocele. Other intra-abdominal organs and vessels were normal; there was neither intra-abdominal mass nor ascites. The association of asymmetry growth, epidemics naevus, lipoma, macrocephaly and bony abnormalities contributed in making the diagnosis of PS.
After management of acute complications and prolong dietary treatment, there was an improvement of general and nutritional status of the patient. After one year, a surgical excision of the gluteal and thigh mass was done (
The result was satisfactory with esthetical and functional improvement (
An eight years old boy, only child from the mother, was admitted with history of coma and febrile convulsions. At admission, examination found frank meningeal syndrome. Cerebro-spinal fluid analysis showed high protein level and
discrete leucocytosis with mostly lymphocytosis. The diagnosis of viral meningo-encephalitis was retained.
Blood culture was negative. Few days after hospitalization, the patient developed varicella. Examination shows numerous morphological abnormalities: right hemi thorax soft tissue overgrowth, with a verruca naevus adjacent but extending down to the abdomen; there was coexisting hypertrophy of the right buttocks and the right foot (
Cerebral CT scan (
• an important compressive bi-cerebral hygroma of 13 mm thickness;
• bilateral capsular lacuna;
• third ventricular hydrocephaly;
• multifocal arterio-veinous malformations.
The concomitant presence of naevus, asymmetrical growth, lipoma and vascular abnormalities called for PS.
Evolution was stagnant with no recovery of the level of consciousness with persistent convulsive crisis despite permanent anti-convulsive therapy. There was improvement in temperature. Patient was discharged against medical advice on relatives’ request.
PS is a rare disease of unknown aetiology. It is part of malformative syndrome with excessive growth and frequently associated with genetic anomalies [
mutation AKTI was in all patients with PS [
A review of 250 cases was separately published by some authors who decided to apply the already existing criteria to those different cases. Only 47.3% of patients were considered reel cases of PS [
To make a diagnosis of PS, one must have all the general criteria, and various specific criteria
*Adapted from Biesecker publication [
Growth anomalies, like others signs are generally absent at birth. They appear and increased progressively and could affect all part of the body; limbs, sensory organs, (ears in our first patient), deep organs could be asymmetric. Involvement of visible part could be disgracing.
Lipomatous overgrowths are frequent and could simulate a royal tumour or carcinomatous degeneration in these polymorphic syndromes [
Clinical presentation varied extremely in different cases published involving both children and adults [
Differential diagnostic could be made with others syndromes with the triads: growth anomalies, cutaneous signs, and vascular malformations. Could be cited: type 1 neurofibromatosis (NF1), body hemi-hypertrophy and multiple lipomatous syndrome (HHML) [
The fact that PS is part of a big group of pathology caused by somatic mosaic mutation and not hereditary must lead to be careful in making the diagnosis. In fact, the relationship between somatic mutation and carcinoma has been largely
| General criteria | Mosaic distribution of lesions Sporadic occurrence Progressive course |
|---|---|
| Specific criteria | A: 1) Cerebriform connective tissue nevus B: 1) Linear epidermal nevus 2) Asymmetric, disproportionate overgrowth 3) Specific tumors before 2nd decade (Bilateral ovarian cystadenoma; Parotid monomorphic adenoma) C: 1) Dysregulated adipose tissue 2) Vascular malformations 3) Lung cysts 4) Facial phenotype |
studied and lists of complete oncogenes or tumour suppressor genes known to be mutated in cancers has been described [
PS complications depend on the existing anomalies, but it is known that the major risks are deep venous thrombosis and tumours. Pulmonary embolism is a frequent complication in patients, implicating the necessity of careful precautions, especially during surgery. The two principal tumours known to be part of specific diagnostic criteria are bilateral ovarian cyst adenoma and parotids glands monomorphic adenoma. A recent publication suggested some immune disturbances related to PS [
PS is a pathology which could be incapacitating. It exposes to a high risk of benign tumours and deep venous thrombosis. The variability of abnormalities and the risks incurred required multidisciplinary management.
Kissou, S.-L.A., Tankoano, A., Somé, O.R., Ouédraogo, A.N., Dakouré, P.W.H., Nikiema, Z. and Nacro, B. (2018) Proteus Syndrome: About Two Paediatrics Cases. Open Journal of Pediatrics, 8, 42-49. https://doi.org/10.4236/ojped.2018.81006