| Abstract|| |
Proteus syndrome is one of the very rare syndromes with occurrence of cerebriform connective tissue nevus. The aim of the present manuscript was to present a case of Proteus syndrome in an unusual facial location, which to the best of our knowledge, is being reported for the first time. The unusual occurrence further strengthens the mosaical basis of its etiopathogenesis.
Keywords: Cerebriform connective tissue nevus, facial palsy, forehead, fronto-temporal, Proteus syndrome
|How to cite this article:|
Balaji S M. Fronto-temporal cerebriform connective tissue nevus in Proteus syndrome. Indian J Dent Res 2014;25:828-31
Cerebriform connective tissue nevus (CCTN) is a hallmark feature of Proteus syndrome and is a hallmark diagnostic feature.  Proteus syndrome is a rare, genetic disorder arising out of mutation of AKT1 oncogene in a mosaic pattern that is latter manifested either as/or by a disproportionate overgrowth of the skeletal system, tumor predisposition, and dermatological abnormalities during the postnatal development. The CCTN is frequently observed in patients.  The CCTN necessarily does not present at birth but manifests later in childhood. 
The aim of the manuscript was to present a case of Proteus syndrome where the presence of a solitary CCTN in a previously unreported location - the forehead and its successful surgical management.
| Case report|| |
A 17-year-old female sought treatment for a growth in the forehead. The growth was slowly growing from the 1 st year of life to present size and had led to nonfunctioning of facial muscles besides esthetical concern. History revealed that her parents were not biological relatives, and the family had no history of siblings or any first or second-degree relatives being affected with a similar condition. She has a younger sister who is apparently healthy. Her parents revealed that there was no noticeable growth in the region at birth. The onset was insidious, by about the 1 st year of life, there was a slight elevation along the midline. Her parents also noticed insignificant difference in growth of the right and left sides of the skull. They did not seek any medical advice for the same till date. The growth was not significant till age of ten after which there was a significant enlargement of the condition to its present status. She attained menarche by 12 years of age and no sudden spurt of size of the lesion noted around the period.
On examination, a single, cerebriform (brain-like) lesion with deep brown color, raised, rugose, thick growth thrown into folds were seen along the root of the nose along the forehead, measuring about 3.5 cm in length × 2 cm in width and 1.5 cm in height. The growth was centered along the midline. There was a noticeable facial asymmetry noted. The left side of the face was relatively larger than the right half. The muscles of facial expression along the left side were weak and were not responsive, confirming certain degrees of facial paralysis.
On a closer inspection, the superficial skin on the left side was comparatively darker and coarser than the right side. There were numerous pinpoint elevations found on the skin along the left side. The change was noticeable in all exposed parts of the body. Distribution of hairs was normal on both sides. Numerous, dark brownish spots with rough margins of varying sizes were noted [Figure 1]. On palpation, no difference in temperature variation between both halves was noted. The texture was leathery. Her sensation over the skin was normal. Structures of face, legs, knee, and back were relatively enlarged on the left side. Nasal deviation to the right side was noted. Furthermore, the left ear was relatively larger [Figure 2]. Intra-orally she had a normal complement of teeth set. The left side teeth size was enlarged relatively to the right quadrants. Along the left side, gingival hyperplasia, tongue, upper and lower lips were enlarged.
|Figure 1: Gradual increase in the size of the growth from 1st year of life to present size leading to non-functioning of facial muscles|
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|Figure 2: Dark and coarse superficial skin in the left side compared to the right side. Note the numerous pin-point elevations in the affected left side|
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The computed tomography study showed expansion of the left frontal, parietal, temporal, and occipital bones with matrix in the diploic space and thinning of the outer table. Calcified lesions were also observed along the inner table of the left frontal bone and along the anterior interhemispheric fissures. These radiological impressions suggested an osteodystrophy with a possibility of calcified meningiomas [Figure 3].
|Figure 3: Expansion of the left frontal, parietal, temporal and occiptal bones with matrix in the diploic space and thinning of the outer table|
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Based on this presentation, several disorders including craniofacial dysplasia, hemihyperplasia, and hemihyperplasia/lipomatosis syndrome were considered. Based on the disproportionate, asymmetric, progressive, distorting localized growth, a diagnosis of Proteus syndrome was given, and the single lesion diagnosed as CCTN.
As there was patient more concerned with esthetics due to the growth, it was carefully excised under general anesthesia after standard preparation. The gap was approximated and closed in layers [Figure 4]. The histopathological examination confirmed the diagnosis of a nevus. A standard facial reanimation surgery using the static-sling approach was performed. Standard pinna reduction was carried out [Figure 5] and [Figure 6]. The patient refused to undergo correction of the nose and skull deformities. She was referred for neurological opinion and is under observation for the same. The patient is currently without any new lesion and is under observation for the past 2 years [Figure 7].
|Figure 4: Under GA, the entire growth was carefully excised and the wound closed in layers. Note the excised portion|
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|Figure 5: Standard facial reanimation surgery using the static- sling approach done|
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|Figure 6: Standard pinna reduction procedure by comparing with the unaffected side|
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|Figure 7: Immediate postoperative view and postoperative view after 1 year follow up showing complete healing and no recurrence|
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| Discussion|| |
Proteus syndrome is rare congenital disorder of genetic origin that is believed to be hamartomatous in nature. It was first described in 1979 by Cohen and Hayden, and named as such in 1983 by Wiedeman. The syndrome causes malformations by a progressive, asymmetric, excessive, and multifocal growth of tissues. The condition is characterized by partial gigantism of the involved regions, pigmented nevi, subcutaneous tumors, macrocephaly, and visceromegalies, but normal mental development. ,, All the conditions mentioned in the literature have been observed in the present case.
This article reports a case of Proteus syndrome in a 17-year-old female patient. This is a unique case in the family, whose onset started at 1-year after birth as a growth in the forehead. During childhood, the patient experienced disproportionate growth of the facial skeleton. The neuropsychomotor development is normal. The syndrome diagnosis was established by the above-mentioned clinical findings associated with lesion presentation pattern, which are: Mosaic distribution, progressive course, and sporadic occurrence. The patient came to the clinic complaining of lesion that was diagnosed as CCTN, facial paralysis, and generalized facial asymmetry. 
The pathogenesis of Proteus syndrome occurs very early in utero life. The AKT1 sporadic mutation occurs in few cells, and the progeny of these cells is widely distributed. This in latter life manifests as the growths and CCTN. Furthermore, this leads to remarkably high variety and degrees of clinical manifestations of Proteus syndrome. Such manifestations lead to difficulties in attaining a diagnosis. The diagnostic criteria for Proteus syndrome were reviewed in 1999. The mosaic distribution pattern of the lesions, progressive course, and sporadic occurrence are mandatory characteristics. Among the specific criteria, connective tissue nevi, when present, are almost pathognomonic. The other findings, when combined, can help to establish the diagnosis, such as the presence of two of the following: Epidermal nevi; disproportionate overgrowth of limbs, vertebrae, or viscera; macrocephaly or hyperostosis; bilateral ovarian cystadenoma or monomorphic adenoma of the parotid gland; or three of the following adipose tissue dysregulations, vascular malformations, or facial phenotypes. , In the present case, most of the features are present that has led to this diagnosis.
Differential diagnoses of this condition would include various vascular and pigmented syndromes and lipomatoses, mainly Klippel-Trenaunay syndrome and hemihyperplasia/lipomatosis syndrome. Furthermore, craniofacial fibrous dysplasia also needs to be considered. The radiological impressions were consistent with the craniofacial fibrous dysplasia.  There are reports of isolated CCTN in the fronto-occipital region. However, in such isolated cases, there are no other additional findings reported. The presence of the segmental hypertrophy, cerebral calcifications, hyperostosis all are additional findings of the Proteus syndrome.
The present case was challenging diagnostically as the site - CCTN in fronto-occipital (forehead) region has not been reported nor was associated facial palsy not reported earlier. Isolated presence of CCTN has been reported on the same site.  However, the presence of asymmetrical, progressive, multifocal lesion, and growth gave the clue to the diagnosis. The histopathological confirmation of nevus helped to give the final diagnosis.
The complete treatment of this condition is multidisciplinary, including clinical and psychological support. Proteus syndrome often causes significant social stigma, due to its rarity and disfiguring features. The CCTN has been documented to slowly expand previously uninvolved skin, increased thickness, and development of new lesions.  The skeletal overgrowth can result in biomechanical dysfunction and functional limitation as seen in the present case. Till date, no association of the condition with facial paralysis has been described. As the patient refused elaborate treatment, only cosmetic correction was possible. However, the patient was warned about the potential neurological complication and possible growth of new lesions. The patient is being followed up uneventfully.
| Conclusion|| |
A variation of presentation of Proteus syndrome with predominant manifestations seen in head and neck is presented. Further the need to consider this syndrome when multiple progressive, asymmetric growth or CCTN presents in the patient. The esthetical management of the case to acceptable levels has been presented.
| References|| |
Cohen MM Jr. Proteus syndrome: An update. Am J Med Genet C Semin Med Genet 2005;137C: 38-52.
Beachkofsky TM, Sapp JC, Biesecker LG, Darling TN. Progressive overgrowth of the cerebriform connective tissue nevus in patients with Proteus syndrome. J Am Acad Dermatol 2010;63:799-804.
Sene LS, Sales Pde O, Chojniak R. Proteus syndrome: Case report. Rev Assoc Med Bras 2013;59:318-20.
Pai VG, Rao GS. Congenital cerebriform melanocytic naevus with cutis verticis gyrata. Indian J Dermatol Venereol Leprol 2002;68:367-8.
S M Balaji
Director and Consultant Maxillofacial Surgeon, Balaji Dental and Craniofacial Hospital, Chennai, Tamil Nadu
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]