Case No. :	21
Month :	September
Year :	2000
Contributor :	Dr. Hemant Parmar

Clinical Profile | Radiological Findings | Discussion

Clinical Profile:

A four-month-old girl presented for investigation of repeated attacks of seizures, extensive facial abnormalities and protruding right eyeball. She was the first child of non-consanguineous parents. The baby did not cry immediately after the birth. However, the five minute APGAR score was 9/10.

Physical examination revealed right hemifacial and calvarial enlargement, soft tissue swelling over the right side of face and neck, macrocephaly, right facial palsy, right proptosis, hypertrophy of the right upper limb, hyperpigmented skin lesions on the face, trunk and back and protuberant abdomen. Head control was still not achieved. Ophthalmologic examination revealed bilateral optic atrophy.

Fig.1 : Contrast enhanced axial CT scan of brain showing increased amount of white matter with hypodensity and pachygyria in the right frontal region with markedly enlarged right frontal horn. Note hyperostosis of right sided bones.

 

Fig 2 : Increased size of right frontal , parietal and occipital lobes is seen with dilatation of the right lateral ventricle. Note hypodensity of white matter on right side. The parallel orientation of the body of the left lateral ventricle suggested the possibility of anomaly of the corpus callosum.

 

Fig.3 : Proptosis of the right eyeball is seen with hypertrophy of the right frontal, zygomatic and sphenoid bones. A fatty mass lesion is seen on the right side, involving the subcutaneous tissues. Right parapharyngeal space also shows fatty areas. The pharynx is pushed towards the left side.

 

Fig.4 : Predominantly fatty, inhomogeneous mass lesion involving the right side of face with few intensely enhancing areas within it. Note the right mandibular hyperplasia, right maxillary exostosis, enlarged tongue and part of the enlarged right upper limb.

 

Radiological Findings :

Ultrasonography (not shown) of the abdomen revealed a hyperechoic lesion in the right lobe of the liver, which was reported as hemangioma on histopathological study. The neck lesion was reported as lymphangioma with predominant adipose tissue.

A CT scan(Figs. 1,2,3,4) revealed a large right sided fibro-fatty mass lesion with infiltration of the right parapharyngeal, parotid and premaxillary spaces. Minimal infiltration of the posterior triangle of the neck was also seen. The tongue was hypertrophied. The right mandible, maxilla, zygoma, greater wing of the sphenoid, orbital walls and frontal bone were hypertrophied. Marked proptosis was seen on the right side , due to hypertrophy and hyperostosis of the maxillary, sphenoid, zygomatic and frontal bones. A sessile exostosis was seen arising from the right maxilla. The pharynx was slightly displaced towards left side. The occipital bone was relatively of normal size. There was no evidence of craniostenosis in any of the sutures. Few areas of skull vault hyperostosis were also detected in the right frontal region.

The right frontal, parietal and occipital lobes were markedly enlarged in size. However, the size of right temporal lobe was relatively normal. The right frontal, occipital horns and body of the lateral ventricle along with the third ventricle were enlarged in size (Fig. 1,2). Temporal horns and fourth ventricles were normal bilaterally. Minimal enlargement of the left frontal horn and body of the lateral ventricle was also noted. Areas of pachygyria were clearly seen in the right frontal and occipital lobes. Few areas of cortical thickening were also seen in right occipital lobe, suggestive of areas of polymicrogyria. The amount of white matter was increased on the right side, compared to the opposite left side. The parallel orientation of the bodies of the lateral ventricles suggested the possibility of anomalous corpus callosum (Fig. 2).

The patient was put on anti-convulsion therapy. The frequency of seizures decreased thereafter.

The clinical and radiological features are classical of the Proteus syndrome.

Differential Diagnosis and Discussion :

Proteus syndrome is thought to occur due to a lethal somatic gene mutation that leads to a mosaic state, which allows survival and can explain the sporadic occurrence, equal sex ratio and variable extent of involvement of organs and body . Mental retardation and seizures are common clinical features . Typical facies like an elongated face with dolichocephaly, downward slanting of the palpebral fissures, mild ptosis, low nasal bridge and open mouth at rest have been described previously . Evolution and progression of clinical manifestations due to various abnormalities is very characteristic of Proteus syndrome.

Among the brain anomalies, hemimegalencephaly was seen in about 10 patients with Proteus syndrome and can cause secondary generalised calvarial remodelling . Hemimegalencephaly can occur as an isolated abnormality or may be associated with Klippel - Trenauney- Weber syndrome , neurofibromatosis, tuberous sclerosis, hypomelanosis of Ito and linear sebaceous nevus syndrome (of Jodassohn), which is a type of epidermal nevus syndrome . Cutaneous pigmentation disorders are also seen in many of these conditions, as seen in this case. Ventricular dilatation in the larger hemisphere is also reported previously. Associated migrational anomalies like gray matter heterotopia, polymicrogyria, pachygyria, lissencephaly etc. are frequently seen. Calcified subependymal nodules and periventricular cysts have also been described. Such nodules are also seen in tuberous sclerosis. Corpus callosal abnormalities such as absence and thickening have also been documented, in a case similar to or probably variant of Proteus syndrome. Schizencephaly and Dandy walker malformation are also reported with this syndrome. At least 4 cases revealed hypodense periventricular white matter, as seen in our case . Hemimegaly of the optic nerve and occipital dysmyelination have also been reported . Frontal white matter calcifications and vascular abnormalities are also described with this syndrome. Preoperative vascular assessment is therefore recommended to prevent the risk of considerable bleed in patients undergoing hemispherectomy . Dural sinus thrombosis and other dural sinus abnormalities can be seen in both Proteus syndrome and epidermal nevus syndrome . Two cases of microcephaly are also described with this syndrome . Intracranial neoplasms may be part of hamartromatous nature of the disease. three cases of meningioma, one case of optic nerve tumour and one case of pinealoma have been reported previously .

Bony abnormalities are often seen to involved facial bones and calvaria. Frontal bossing, diffuse enlargement and exostoses can be seen in skull, as seen in our case. Exostosis may involve fronto-parietal or parieto-occipital regions ("Buckleschdel" or haunched skull), external auditory canals, the bridge of the nose and the alveolar ridges . Calvarial bony exostosis are common abnormality in this syndrome. Craniostenosis with involvement of the coronal, lambdoid, sagittal and metopic sutures have been described . Marked facial abnormalities are seen due to common involvement of the maxilla and mandible. Mandibular asymmetry and unilateral condylar hyperplasia are common, as in this case . High arched palate and crowding of the teeth are also seen . Combination of hemimegalencephaly and limb overgrowth as seen in our case can also occur with Klippel-Trenauney - Weber syndrome .

Subcutaneous masses are often seen to be involving neck and face, as other parts of the body. Lymphangiomas, haemangiomas and lipomas are more common. These may develop suddenly and grow quickly in proteus syndrome. Infiltration of the various neck spaces is commonly seen. Early resection is advised to avoid airway compromise due to haemorrhage and sudden expansion . Monomorphic adenomas of the parotid gland have been reported in two cases . Displacement of the pharynx and air-way along with enlarged tongue muscles on one side, as seen in this case is also reported previously .

The differential diagnosis of Proteus syndrome includes other hamartoses like and causes of hypertrophy like. With CNS involvement, many entities are excluded, leaving mainly other meurocutaneous syndromes as diagnostic possibilities. Encephalocraniocutaneous lipomatosis also shows unilateral CNS findings and was thought to be a localised form of Proteus syndrome. But, hemimegalencephaly is probably not a finding in this entity . Many of the features are similar in both the entities.