ParryRomberg syndrome (also known as progressive hemifacial atrophy) is a rare neurocutaneous syndrome characterized by progressiveshrinkage and degeneration of the

tissues beneath the skin, usually on only one side of the face (hemifacial atrophy) but occasionally extending to other parts of the body.[1] An autoimmune mechanism is suspected, and the syndrome may be a variant of localized scleroderma, but the preciseetiology and pathogenesis of this acquired disorder remains unknown. It has been reported in the literature as a consequence of sympathectomy. The syndrome has a higher prevalence in females and typically appears between 5 15 years of age. In addition to the connective tissue disease, the condition is often accompanied by significant neurological, ocular and oral signs and symptoms. The range and severity of associated symptoms and findings are highly variable.

Skin and connective tissues[edit]

An axial CT scan of a 17-year-old girl with ParryRomberg syndrome, showing severe loss of subcutaneous tissue and muscle of the right side of the face, with no apparent involvement of the facial bones

Initial facial changes usually involve the area of the face covered by the temporal or buccinator muscles. The disease progressively spreads from the initial location, resulting in atrophy of the skin and its adnexa, as well as underlying subcutaneous structures such as connective tissue, (fat, fascia,cartilage, bones) and/or muscles of one side of the face.[2] The mouth and nose are typically deviated towards the affected side of the face.[3] The process may eventually extend to involve tissues between the nose and the upper corner of the lip, the upper jaw, the angle of the mouth, the areaaround the eye and brow, the ear, and/or the neck.[2][3] The syndrome often begins with a circumscribed patch of scleroderma in the frontal region of the scalp which is associated with a loss of hair and the appearance of a depressed linear scar extending down through the midface on the affected side. This scar is referred to as a "coup de sabre" lesion because it resembles the scar of a wound made by a sabre, and is indistinguishable from the scar observed in frontal linear scleroderma.[4][5]

In 20% of cases, the hair and skin overlying affected areas may become hyperpigmented or hypopigmented with patches of unpigmented skin. In up to 20% of cases the disease may involve the ipsilateral (on the same side) or contralateral (on the opposite side) neck, trunk, arm, or leg.[6] The cartilage of the nose, ear and larynx can be involved. The disease has been reported to affect both sides of the face in 5-10% of the cases.[4] Symptoms and physical findings usually become apparent during the first or early during the second decade of life. The average age of onset is nine years of age,[2] and the majority of individuals experience symptoms before 20 years of age. The disease may progress for several years before eventually going into remission (abruptly ceasing).[2]

Neurological[edit]
Neurological abnormalities are common. Roughly 45% of people with ParryRomberg syndrome are also afflicted with trigeminal neuralgia (severe pain in the tissues supplied by the ipsilateraltrigeminal nerve, including the forehead, eye, cheek, nose, mouth and jaw) and/or migraine (severe headaches that may be accompanied by visual abnormalities, nausea and vomiting).[6][7] 10% of affected individuals develop a seizure disorder as part of the disease.[6] The seizures are typically Jacksonian in nature (characterized by rapid spasms of a muscle group that subsequently spread to adjacent muscles) and occur on the side contralateral to the affected side of the face.[2] Half of these cases are associated with abnormalities in both the gray and white matter of the brainusually ipsilateral but sometimes contralateralthat are detectable on magnetic resonance imaging (MRI) scan.[6][8]

Ocular[edit]
Enophthalmos (recession of the eyeball within the orbit) is the most common eye abnormality observed in ParryRomberg syndrome. It is caused by a loss of subcutaneous tissue around the orbit. Other common findings include drooping of the eyelid (ptosis), constriction of the pupil (miosis), redness of the conjunctiva, and decreased sweating (anhidrosis) of the affected side of the face. Collectively, these signs are referred to as Horner's syndrome. Other ocular abnormalities include ophthalmoplegia (paralysis of one or more of the extraocular muscles) and other types ofstrabismus, uveitis, and heterochromia of the iris.[9][10]

Oral[edit]
The tissues of the mouth, including the tongue, gingiva, teeth and soft palate are commonly involved in ParryRomberg syndrome.[3] 50% of affected individuals develop dental abnormalities such as delayed eruption, dental root exposure, or resorption of the dental roots on the affected side. 35% have difficulty or inability to normally open the mouth or other jaw symptoms, includingtemporomandibular joint disorder and spasm of the muscles of

mastication on the affected side. 25% experience atrophy of one side of the upper lip and tongue.[6]

Causes[edit]
The fact that some people affected with this disease have circulating antinuclear antibodies in their serum supports the theory that ParryRomberg syndrome may be an autoimmune disease, specifically a variant of localized scleroderma.[11] Several instances have been reported where more than one member of a family has been affected, prompting speculation of an autosomal dominant inheritance pattern. However, there has also been at least one report of monozygotic twins in which only one of the twins was affected, casting doubt on this theory. Various other theories about the etiology and pathogenesis have been suggested, including alterations in the peripheral sympathetic nervous system (perhaps as a result of trauma or infection involving thecervical plexus and/or the sympathetic trunk), as the literature reported it following sympathectomy, disorders in migration of cranial neural crest cells, or chronic cellmediated inflammatory process of the blood vessels. It is likely that the disease results from different mechanisms in different people, with all of these factors potentially being involved.[2]

Diagnosis[edit]
Diagnosis can be made solely on the basis of history and physical examination in people who present with only facial asymmetry. For those who report neurological symptoms such as migraine or seizures, MRI scan of the brain is the imaging modality of choice. A diagnostic lumbar puncture and serum test for autoantibodies may also be indicated in people who present with a seizure disorder of recent onset.[6]

Management[edit]
Medical[edit]
Medical management may involve immunosuppressive drugs such as methotrexate, corticosteroids, cyclophosphamide, and azathioprine. No randomized controlled trials have yet been conducted to evaluate such treatments, so the benefits have not been clearly established.[6]

Surgical[edit]
Affected individuals may benefit from autologous fat transfer or fat grafts to restore a more normal contour to the face. However, greater volume defects may require microsurgical reconstructive surgery which may involve the transfer of an island parascapular fasciocutaneous flap or a free flap from the groin, rectus abdominis muscle (Transverse Rectus Abdominis Myocutaneous or "TRAM" flap) or latissimus dorsi muscle to the face. Severe deformities may require additional procedures, such as pedicled temporal fascia flaps, cartilage grafts, bone grafts, orthognathic surgery, and bone

distraction.[12] The timing of surgical intervention is controversial; some surgeons prefer to wait until the disease has run its course[3] while others recommend early intervention.[13]

Epidemiology[edit]
ParryRomberg syndrome appears to occur randomly and for unknown reasons. Prevalence is higher in females than males, with a ratio of roughly 3:2. The condition is observed on the left side of the face about as often as on the right side.[14]

History[edit]
The disease was first described in 1825 by Caleb Hillier Parry (1755 1822), in a collection of his medical writings which were published posthumously by his son Charles Henry Parry (1779 1860).[15] It was described a second time in 1846 by Moritz Heinrich Romberg (1795 1873) and Eduard Heinrich Henoch (1820 1910).[16] German neurologist Albert Eulenburg (1840 1917) was the first to use the descriptive title "progressive hemifacial atrophy" in 1871.[17][18][19]

Progressive hemifacial atrophy (Parry-Romberg Syndrome)

S. A. Deshingkar, S. R. Barpande, [...], and J. G. Humbe
Additional article information

Abstract
Progressive hemifacial atrophy, also known as Parry-Romberg Syndrome, is an uncommon degenerative and poorly understood condition. It is characterized by a slow and progressive atrophy affecting one side of the face. The incidence and the cause of this alteration are unknown. A cerebral disturbance of fat metabolism has been proposed as a primary cause. This can be result of a trophic malformation of cerebral sympathetic nervous system. Possible factors that are involved in the pathogenesis are trauma, viral infections, heredity, endocrine disturbances, and autoimmunity, among others. Characteristically, atrophy progresses slowly for several years and, soon after, it become stable. The purpose of this work is, through the

presentation of a clinical case, to accomplish a literature review concerning general characteristics, etiology, pathophysiology, differential diagnosis, and treatment of progressive hemifacial atrophy.
Keywords: Hemifacial atrophy, Parry-Romberg syndrome, scleroderma

Introduction
Progressive hemifacial atrophy, also known as Parry-Romberg Syndrome, is an uncommon degenerative condition characterized by a slow and progressive atrophy, generally unilateral, of facial tissues, including muscles, bones, and skin.[1] It was first described by Caleb Hillier Parry in 1825 and later in more detail by Moritz Heinrich Romberg in 1846.[2] More than an esthetic trouble, this illness brings several functional and psychological problems, when a symmetric face loses its identity. Characteristically, there is regional atrophy of skin, subcutaneous tissue, and musculature. When the onset is before the second decade of life, the underlying bone and cartilage may also be involved.[3] A sharply demarcated line between normal and abnormal skin develops, so called coup de saber, and the involved area varies from a discrete lesion to a widespread, extensive malformation. Alopecia and pigmentation of the involved skin often appear.[3] The other important features of this pathology are the enophthalmy, the deviation of mouth and nose to the affected side, and unilateral exposition of teeth, when lips are involved.[3] In addition to the obvious facial atrophy, a variety of accompanying conditions have been reported; ocular changes in 10% to 35% of cases; neurologic disturbances, which include focal epileptiform seizures and trigeminal neuralgia; and ipsilateral progressive body atrophy. Oral manifestations

include atrophy of half of the lip and tongue, shortening of the body of the mandible and/or ramus of the mandible, retarded tooth eruption, and malformed tooth roots.[3] The objective of this work is to report a clinical case of young male patient with emblematic features of progressive hemifacial atrophy along with discussion concerning general characteristics, etiology, pathophysiology, and treatment of progressive hemifacial atrophy.

Case Report
In 2008, a 13-year-old boy was referred to Department of Oral Pathology, Government Dental College and Hospital, Aurangabad, Maharashtra, with a complain of progressive deformity of left side of face since 5 to 6 years. During the physical examination, it was noted that this patient presented a facial asymmetry with marked hypoplasia of the left side of the face, deviation of lips and nose toward left side, and enophthalmy in left eye region [Figures [Figures11 and and2].2]. A big linear dark scar (coup de sabre) was present in the left side of mandibular mentum region passing upward to involve lips and left ala of nose producing obvious depression [Figure 3]. The notching of the upper and lower lip leads to exposure of anterior teeth on left side. Alopecia was noticed in the region of left eyebrow toward medial side [Figure 1]. Patches of hyperpigmentation were seen on the skin of affected area. In addition, ear on left side was slightly smaller than that of right side.

Figure 1 Marked hypoplasia of the left side of the face with deviation of lips and nose toward left side and notching of lips and nose with exposure of teeth. Alopecia in left eyebrow region

Figure 2 Hypoplasia of the left side of face with enopthalmy in left eye region

Figure 3 A big linear dark scar (coup de sabre) in the left side of mandibular mentum region

Intraorally, the most relevant alteration was the unilateral atrophy of tongue papillae of left side [Figure 4]. There was over-retained maxillary left deciduous canine with palatally erupted permanent canine leading to crowded left maxillary arch. The occlusion was disturbed with midline shifted to the left side. Also, there was hypoplasia of maxillary anterior teeth [Figure 5].

Figure 4 Unilateral atrophy of tongue papillae of left side

Figure 5 Hypoplasia of maxillary anterior teeth and deviation of midline to left side

Radiographically, an abnormal root development was seen with maxillary left premolars. The over-retained root pieces of deciduous mandibular second molar of left side were seen on mesial and distal side of roots of second

premolar. The overall eruption pattern of teeth on left side was retarded as compared to that of right side. The mandible showed decreased vertical height of ramus along with loss of gonial angle prominence on the affected side [Figure 6].

Figure 6 Retarded eruption pattern of teeth on left side compared to that of right side. Decreased vertical height of ramus along with loss of gonial angle prominence on the affected side

The patient presented with good general health condition without any history of obvious past illness that would explain the cause of facial asymmetry. With these clinical and radiologic findings, the diagnosis of progressive hemifacial atrophy was made. At present, the patient is being periodically reviewed until atrophic manifestation stops and specific intervention could be accomplished.

Discussion
Progressive hemifacial atrophy, as described in the case above, is a rare pathology, of unknown cause, whose degenerative condition affect not only the esthetic but also the functionality of the attained hemiface. The etiology of hemifacial atrophy has been the subject of numerous theories, which include heredity, viral infection, trauma, endocrine disturbances, autoimmunity, sympathetic malfunctions, trigeminal neuritis, and association with a connective tissue disorder, particularly scleroderma.[1,3] A cerebral disturbance on fat metabolism has also been proposed as a primary cause.[1]

However, none of the theories withstands thorough investigation, and currently the cause of hemifacial atrophy remains unresolved. The pathogenesis of progressive hemifacial atrophy is unknown. A supposed neurotrophic pathogenesis was described by Cassirer in 1912.[4] He proposed that the atrophic disease process follows the pattern of trigeminal nerve innervation. Certain studies suggested that the disorder was familial one.[4] The anatomic changes of Parry-Romberg Syndrome impact the growth potential of hard tissue, preventing an increase in size during active growth periods. The associated soft tissues shrink by loss of adipose tissue.[4] Hence, atrophy that started in the second decade of life is less noticeable because facial growth is nearly complete. Early disease onset and long duration cause greater deformity. Frequently, the onset of Parry-Romberg Syndrome occurs along first and second decades of life.[5] This syndrome seems to have higher incidence among women and affect left side of face most often.[5] Characteristically, the atrophy progresses slowly over many years and, then, it become stable.[1] Alternatively, the condition may burn itself out at a very early stage and result in minimal deformity.[3] Alterations concerning involvement, duration, and deformity can stabilize in any stage of growing and development. The extension of the atrophy is frequently limited to on one side of the face, and the ipsilateral involvement of body is rare.[1] Clinically, the skin can be dry and with a dark pigmentation. Some patients present a demarcation line between normal and abnormal skin, reminding a big linear scar, known as coup de saber, as could be noticed in this patient.[1,6] Ocular involvement is common, and the most frequent manifestation is the enophthalmy, due to fat loss around the orbit, as was

observed in the present case. The eye usually works normally. There may be localized areas of alopecia as was observed in present case in the region of left eyebrow. Occasionally, there may be some neurological complications, such as trigeminal neuralgia, facial paresthesia, severe headache, and contralateral epilepsy.[1,6] These complications were not discerned in the present case. Mouth and nose are deviated to the affected side, deviating also facial and dental midlines. Atrophy of superior lip led the anterior teeth to be exposed, and there may be also unilateral atrophy of tongue.[1,6] The present case showed clearly those features of facial asymmetry, atrophy of lingual papillae; however, atrophy of the tongue was absent. Radiographically, teeth on affected side can present some deficiency in root development and, consequently, delayed eruption.[7] However, the affected teeth are normal and vital clinically.[1,8] This situation occurred with the reported case, as two of the teeth on the affected side presented a malformation of their roots. Also, there was over-retention of deciduous canine causing delayed eruption of permanent successor and dental crowding. Very often, there is unilateral posterior crossbite, as a result of jaw hypoplasia and delayed teeth eruption.[8] The intraoral soft tissue and chewing muscles are usually normal without any movement, speech, or deglutition implications.[1] Histologically, atrophy of epidermis, dermis, and subcutaneous tissue is observed.[1,5] Variable infiltrate of lymphocytes and monocytes at dermis and lack of subcutaneous fat in the affected tissue are also characteristic.[1] Besides, degenerative alterations can be identified on vascular endothelium in electron microscopy.[9]

Differential diagnoses include hemifacial microsomia (first and second branchial arch syndrome) and its variants, such as Goldenhar syndrome, but these are congenital and essentially non-progressive conditions. Posttraumatic atrophy and partial lipodystrophy (Barraquer-Simon Syndrome) are also included in the differential diagnosis. However, partial lipodystrophy is usually bilateral and involves primarily the adipose tissue.[9] The relationship between Parry-Romberg Syndrome and localized scleroderma is controversial. It has been suggested that the term ParryRomberg syndrome should be used for progressive hemifacial atrophy without features of cutaneous scleroderma.[10] However, in patients with Parry-Romberg Syndrome, cutaneous changes are also reported.[10] Therefore, localized scleroderma may be preceding lesion of progressive hemifacial atrophy, and in patients with localized scleroderma, hemifacial atrophy may develop in several years.[10] Hence, regarding the clinical findings and clinical course, localized scleroderma and Parry-Romberg Syndromemay represent differential spectra of same disease process.[10,11] Though the relationship between scleroderma and Parry-Romberg Syndrome remains unclear, the former usually responds to drug therapy whereas later is progressive.[9] Parry-Romberg Syndrome is an auto-limitable condition and there is no cure. Affected patients should have multi-disciplinary attendance of physicians, dentists, phonoaudiologists, and psychologists. The treatment is usually based on reposition of adipose tissue that was lost due to atrophy.[12] Autogenous fat grafts, cartilage grafts, silicon injections and prostheses, bovine collagen, and inorganic implants are some alternatives to esthetic correction of the atrophy.[12] Besides esthetic improvement, symptomatic treatment for neurological disorders is indicated.[12] The cosmetic treatment is just

recommended when the illness stops its evolution, so this is the reason why this patient has not been submitted to any surgical intervention yet.

Conclusion
In conclusion, a case of progressive hemifacial atrophy, with its archetypal feature, was discussed. Till recently, the exact etiology and pathogenesis of this degenerative condition have not been elucidated. Many patients present with classic clinical features and there is little intricacy in diagnosis of progressive hemifacial atrophy. Still, some clinical conditions, especially scleroderma, should be kept in mind while dealing with this disorder. Proper diagnosis and multidisciplinary treatment approach is essential for management of progressive hemifacial atrophy.