April 06, 2020
Years published: 1987, 1989, 1996, 1998, 1999, 2003, 2004, 2010, 2013, 2016, 2020
NORD gratefully acknowledges Jon Stone, FRCP, PhD, Consultant Neurologist and Honorary Professor; David Hunt, FRCP, PhD, Consultant Neurologist and Wellcome Trust Senior Clinical Fellow; and Peter Fernandes MRCP, PhD, Department of Clinical Neurosciences, Western General Hospital, Edinburgh, UK, for assistance in the preparation of this report.
Parry-Romberg syndrome is a rare, acquired disorder characterized by slowly progressive shrinkage (atrophy) of the skin and soft tissues of half of the face (hemifacial atrophy). In rare cases, both sides of the face are affected. In some people, atrophy may also affect the limbs, usually on the same side of the body as the facial atrophy. The severity and specific symptoms of Parry-Romberg syndrome are highly variable from one person to another. Additional symptoms can potentially develop in some people including neurological abnormalities or abnormalities affecting the eyes or teeth. Parry-Romberg syndrome usually becomes apparent during the first decade of life or early during the second decade but does occur in adulthood. Most individuals with Parry-Romberg syndrome experience symptoms before the age of 20 years.The exact cause of Parry-Romberg syndrome is unknown and appears to occur randomly for unknown reasons (sporadically).
The symptoms, progression and severity of Parry-Romberg syndrome are highly variable from one person to another and range from mild to severe. It is important to note that affected individuals will not have all the symptoms discussed below. It seems likely that individuals with milder symptoms are much more common than severely affected individuals. Affected individuals should talk to their physician and medical team about their specific case and associated symptoms.
The characteristic symptom of Parry-Romberg syndrome is thinning or shrinkage (atrophy) of various tissues of the face including fat, skin, connective tissues, muscle, and, in some people, bone. The degree of atrophy can vary widely, ranging from mild, barely perceptible changes to significant asymmetry in which one side of the face appears “sunken in”. The progression of atrophic changes can vary as well. Facial atrophy may progress slowly over many years, or more frequently progresses slowly for several years before stopping. If the atrophy stops progressing, it may occasionally reactivate later in life, but this is rare. In other people, the atrophy may progress indefinitely. In some people, when Parry-Romberg syndrome starts at an early age, the progression seems to accelerate more quickly than when it starts later in life.
The initial facial changes associated with Parry-Romberg syndrome usually occur near the middle portion of the face such as the cheek area above the upper jaw bone (maxilla) or between the nose and the upper corner of the lip. As the disease process continues, the upper face (e.g., the areas around the eye, the eyebrow, and the ear) as well as the angle of the mouth and the lower jaw bone (mandible) usually are affected. In some patients, one half of the chin may also be involved. Affected areas undergo shrinkage (atrophy) of tissues beneath the skin (subcutaneous tissue), the layer of fat under the skin (subcutaneous fat), and sometimes underlying cartilage, muscle, and bone. Areas affected by such changes may develop an abnormally sunken appearance. Many individuals may exhibit an unusual bony depression or hollow in the forehead or upper domed portion of the skull, the bony cavity that accommodates the eye (orbit), and/or the lower jawbone (mandible).
In some people, a “line” may form in the area where the atrophic changes on one side of the face meet the normal, unaffected skin on the other side of the face. In some patients, this “line” may be very distinct and runs either vertically or diagonally down the forehead. The abnormal skin is thickened and hardened (sclerosis). This condition may be referred to as linear scleroderma “en coup de sabre” (LSCS–this comes from the French for ‘sabre cut’). LSCS can occur by itself as an isolated finding. According to the medical literature, LSCS is either a separate disorder that overlaps to a large degree with Parry-Romberg syndrome or essentially the same disorder (i.e., different expressions of one disease process or spectrum of disease). The exact relationship of LCSC and Parry-Romberg syndrome is not fully understood but it’s clear that the two commonly co-exist. About one third of people with linear scleroderma on the head or neck have Parry-Romberg syndrome
Progressive atrophic changes associated with the Parry-Romberg syndrome may rarely also cause abnormalities of an ear. In individuals with the disorder, the ear on the affected side may become misshapen and unusually small and may appear to abnormally protrude from the head due to loss of supporting tissue.
In some people, perhaps one in five, the atrophic skin and soft tissue changes associated with Parry-Romberg syndrome may progress to involve the arm, trunk and legs on one side of the body, either the same side (ipsilateral) as the atrophic changes to the face or the opposite side (contralateral).
In addition, many affected individuals also experience abnormal changes affecting the hair on the affected side including the development of abnormal bald patches on the scalp (alopecia), absence of eyelashes, and absence of the middle portion of the eyebrow and/or whitening (blanching) of the hair. In some people, such hair changes may occur before other abnormalities associated with the disorder.
Some individuals with Parry-Romberg syndrome may develop abnormalities affecting the mouth and teeth. Some individuals develop atrophy of half (hemiatrophy) of the upper lip and/or one side of the tongue. In addition, due to progressive atrophic changes associated with the disorder, portions of the lower jaw bone (mandible) may be unusually short on the affected side and the jaw may rarely be prone to spontaneous fracture. The unaffected side of the mouth and nose may sometimes point (deviate) towards the affected side. Some affected individuals may have difficulty opening or closing the jaws. Involuntary contractions of muscles used in chewing (hemi-masticatory spasm or trismus) may occur. One side of the upper lip may have an unusually twisted or raised appearance and certain teeth may be abnormally exposed, erupt unusually late, and/or have atrophic roots. In addition, the upper and lower teeth may meet inappropriately (malocclusion).
Some affected individuals may also experience various neurological symptoms. Migraine headaches (severe headaches accompanied by visual symptoms, light sensitivity, nausea and vomiting) are common in the general population but may be even more common in individuals with Parry Romberg syndrome. Individuals with Parry Romberg syndrome may have more prolonged migraines with associated pupillary abnormalities (the black part of the eye). Less often, perhaps one in ten individuals with Parry-Romberg syndrome can experience episodes of uncontrolled electrical disturbances in the brain (epileptic seizures). In these people, seizure episodes are usually characterized by jerky movements of muscles on the side of the body not affected by hemifacial atrophy. Such seizures, called contralateral focal seizures, are characterized by rapid jerky movements of muscles that may spread up or down a limb. Additional neurological symptoms that may occur include abnormal sensations (e.g., prickling or burning sensations called paresthesia) in the facial area and/or episodes of severe pain in the facial areas supplied by the fifth cranial nerve (trigeminal nerve) including the mouth, cheek, nose, and/or other areas (trigeminal neuralgia). Spasm of the jaw (trismus) sometimes occurs in Parry-Romberg syndrome, typically on the same side as the hemiatrophy. Some patients with neurological involvement may experience weakness of the opposite side of the body.
Individuals with Parry-Romberg syndrome may also experience certain additional skin (dermatological) abnormalities including abnormal darkening or fading of the skin overlying the affected areas (hyper- and hypopigmentation). These skin pigment changes may precede the atrophic symptoms in some people. Rarely, patches of skin on the arms, legs, and/or trunk may have similar pigmentation abnormalities. Some affected individuals have a condition called vitiligo, a skin condition in which loss of color (pigmentation) of areas of skin results in the development of abnormal white patches.
Affected individuals may also develop several eye (ocular) abnormalities. Loss of fat lining the cavity that accommodates the eye (orbit) and loss of bone from the orbit may cause the eye to have an abnormally sunken appearance (enophthalmos). Additional ocular symptoms include displacement of the eyeball farther back in the eye socket than normal (globe retraction), drooping of the upper eyelid (ptosis), different colored eyes (heterochromia), and difficulty closing the eye (lagophthalamos). Some people may have inflammation of the retina (retinitis) or uvea (uveitis) – the iris and middle part of the eye. If the nerves that control eye muscles are involved, then affected individuals may have double vision (diplopia).
Anxiety and depression may accompany Parry Romberg syndrome because of the effect on facial appearance. Although it may be an autoimmune disorder it is not clear whether individuals with the disorder are more likely to have other autoimmune conditions.
The cause of Parry-Romberg syndrome is unknown and appears to occur randomly for unknown reasons (sporadically). Different theories have been proposed to explain the development of the disorder including abnormal development or inflammation of the sympathetic nervous system; viral infections; inflammation of the brain and membranes (meninges) covering the brain (meningoencephalitis); trauma; abnormalities of blood vessel formation (angiogenesis); or autoimmunity.
One specific theory is that inflammation in the nerves that supply skin and fat causes an autoimmune reaction. Autoimmune disorders occur when the body’s immune system mistakenly attacks healthy tissue. The immune system produces specialized proteins called antibodies that destroy foreign materials (e.g., bacteria, viruses, toxins). When antibodies react against healthy tissue, they are known as autoantibodies. There is some evidence from a variety of sources that autoimmune inflammation occurs in Parry-Romberg syndrome, but it is not known if this is the main cause.
Some individuals with Parry-Romberg syndrome have a history of trauma to face or head. Because many individuals with Parry-Romberg syndrome do not have a history of trauma this may be a coincidental finding. More research is necessary to determine what role, if any, that trauma plays in the development of Parry-Romberg syndrome.
Rarely, some individuals with Parry-Romberg syndrome have had relatives with facial asymmetry. However, there is no specific evidence suggesting that a genetic component plays a role in the development of Parry-Romberg syndrome There is also no evidence that it can be passed on to children.
In other types of disorders which affect the soft tissues and sometimes the nervous system, studies in recent years have highlighted the role of ‘somatic mutation’ of genes in causing disease. An example of this is Sturge-Weber syndrome. Somatic mutations are genetic problems that occur during very early development after the sperm has fertilized the egg but when the developing human being is still a ‘ball of cells’. At this very early stage one of these cells can develop a spontaneous genetic mutation which then leads to problems later in cells that derive from this ‘problem’ cell. It is not known whether Parry Romberg syndrome is caused by a somatic mutation, but it is another hypothesis. Disorders caused by somatic mutations will not be passed on to children unless the somatic mutation is also in the sperm or egg which would not be expected in Parry Romberg syndrome.
More research is necessary to determine the specific, underlying cause(s) of Parry-Romberg syndrome. It is possible that the cause may be different in one person than in another and the development of the disorder may require multiple different factors occurring together.
Parry-Romberg syndrome is a rare disorder. The true incidence is unknown. Because the disorder often goes undiagnosed or misdiagnosed determining the true frequency of Parry-Romberg syndrome in the general population is difficult. Physicians studying the disorder have estimated that Parry-Romberg may affect as many as 1 in 250,000 people in the general population. Parry-Romberg syndrome appears to affect women slightly more often than men, but proper studies of the population are lacking. Parry-Romberg syndrome typically becomes apparent during the first or early during the second decade of life, with most affected individuals experiencing symptoms before the age of 20 years. However, the disorder has been described in infants and individuals more than 50 years of age. Parry-Romberg syndrome was originally described in the medical literature in 1825 (C.H. Parry) and 1846 (E. Henoch and H.M. Romberg). There are anecdotal reports of Parry-Romberg syndrome worsening in some pregnant women, either during pregnancy or shortly after childbirth.
A diagnosis of Parry-Romberg syndrome is made based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. The specific tests that are used depend on which symptoms are present and which symptoms occur first. For example, magnetic resonance imaging (MRI) may be used in individuals with neurological symptoms. An MRI uses a magnetic field and radio waves to produce cross-sectional images of organs and bodily tissues. MRI allows better characterization of the soft tissue and bony changes when present. Between 10-20% of individuals with Parry-Romberg syndrome may have changes on brain MRI scans. These changes can include atrophy of the brain on the same side as the facial changes, and sometimes inflammation within the brain itself. Surgical removal and microscopic examination (biopsy) of affected skin tissue may be used in individuals with linear scleroderma en coup sabre.
The treatment of Parry-Romberg syndrome is directed toward the specific symptoms that are apparent in each. Treatment may require the coordinated efforts of a team of specialists. Pediatricians or internists, surgeons (especially plastic surgeons), dentists, ophthalmologists, dermatologists, neurologists, and/or other health care professionals may need to systematically and comprehensively plan an affected individual’s treatment. For example, migraine, epilepsy or uveitis can be treated as they would in any other situation.
A variety of surgical techniques have been used to improve cosmetic appearance in affected individuals. The success rates of these surgical options are highly variable. Surgical treatment is usually not advised until the atrophic changes have ceased and the extent of resulting facial deformity is known. Some doctors advise those with Parry-Romberg syndrome to postpone any surgical procedures until the skull and face are fully developed and the symptoms have subsided for at least a year. Monitoring can be done by having medical photographs taken over a period of time, to be used for comparison. Surgery may leave scar tissue. The effects of this scar tissue on subsequent surgeries should be considered for the final outcome.
Surgical techniques used to treat individuals with Parry-Romberg syndrome include fat or silicone injections, flap/pedicle grafts, or bone implants. These procedures may be effective in achieving cosmetic improvement. It should be noted, however, that fat injections may be reabsorbed when given during the active disease phase. A flap/pedicle procedure is a skin and tissue graft that is left temporarily attached to its original site in order to maintain a constant blood supply while it heals into place.
In some patients, additional measures may help treat certain abnormalities resulting from the disease process. Associated dental abnormalities may be treated with additional surgical and/or other corrective techniques. Additional surgical, corrective, and/or supportive measures may help improve visual problems resulting from hemifacial atrophy. Treatment with anticonvulsant drug therapy may help prevent, reduce, or control seizures potentially occurring in association with the disorder. In addition, in affected individuals with trigeminal neuralgia, certain medications and/or surgical treatments may be beneficial in some cases. (For more information on this disorder, please choose “trigeminal neuralgia” as your search term in the Rare Disease Database.)
Some individuals with severe, progressive Parry-Romberg syndrome have been treated with drugs that suppress the activity of the immune system (immunosuppressive drugs) including methotrexate, corticosteroids, cyclophosphamide, and azathioprine. These have been used because of the hypothesis that Parry Romberg Syndrome is an auto-immune condition and because it overlaps with the inflammatory condition scleroderma ‘en coup de sabre’. It is unclear how beneficial these drugs are, or indeed whether they are beneficial at all. More research is necessary to determine the long-term safety and effectiveness of immunosuppressive drugs in the treatment of Parry-Romberg syndrome. For some patients the use of immunosuppressive drugs may help with controlling seizures, especially when Parry-Romberg syndrome co-exists with linear scleroderma ‘en coup de sabre’.
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