November 19, 2020
Years published: 1989, 1996, 1998, 2006, 2007, 2020
NORD gratefully acknowledges Nicole Choy, MSGC Candidate and NORD Editorial Intern from the Keck Graduate Institute and Emily Quinn, MS, CGC, Associate Program Director, Assistant Professor, Master of Science in Human Genetics and Genetic Counseling (MSGC) program at Keck Graduate Institute School of Pharmacy and Health Sciences, for assistance in the preparation of this report.
Melkersson-Rosenthal syndrome (MRS) is a rare neurological disorder characterized by recurrent, long-lasting swelling of the face (edema), particularly of one or both lips (granulomatous cheilitis), facial muscle weakness (palsy) and deep grooves on the tongue (fissured tongue). Most affected individuals will have only one or two symptoms, while some may present with all three. MRS can affect individuals of all ages. The onset of symptoms is more frequent in young adulthood, but can occur well into adulthood. It is estimated that MRS occurs in 0.08% of the general population. There is no cure for MRS, but symptoms can be treated with anti-inflammatory agents, antihistamines, corticosteroids and in some cases surgery.
Melkersson-Rosenthal syndrome is defined by recurrent swelling (edema) of various facial features such as the upper lip, lower lip, one or both cheeks, eyelids, or rarely, one side of the scalp. It is also characterized by recurrent muscle weakness or paralysis (palsy) in the face and deep grooves or cracks (fissures) in the tongue. Affected individuals usually present with only one or two symptoms. It is estimated that about 8-18% of all patients present with all three symptoms.
The first episode of edema may resolve in a few hours or days, but swelling may be more severe and last longer in subsequent episodes and in some people can become permanent. The enlarged lips may appear cracked and discolored and can be painful. The edema resembles angioedema; rapid swelling caused by an accumulation of fluid, but tends to be more persistent and resistant to antihistamine treatment. Edema associated with MRS may also lead to the development of scar tissue (fibrosis) of the affected tissues. Edema is the most common feature, is often considered the characteristic symptom of MRS and may be the first or only symptom present.
A fissured tongue is defined as grooves on the tongue measuring about 2mm (0.07 in) deep and 15mm (0.6 in) long. A fissured tongue is seen in 30-80% of those affected by MRS and may be present at birth. It may lead to secondary infections, enlargement (hypertrophy) of the tongue, loss of taste buds, or an itching/burning sensation (dysesthesia). Salivary gland secretion may also be reduced. Although associated with MRS, a fissured tongue is also present in about 0.5-5% of the general population and may be familial or hereditary.
Facial muscle weakness and paralysis (facial palsy) occurs in 30-90% of those affected with MRS. It usually occurs after the first few episodes of edema but it can sometimes be the first and only symptom. In 13-50% of affected individuals, facial palsy is associated with facial edema. The facial weakness or paralysis can be on one side (unilateral) or both (bilateral) and resolves initially, but can become permanent. As the disease progresses, the duration of facial palsy may increase. Some individuals may also experience paralysis of other muscles in the head and neck associated with different cranial nerves. Children with recurrent facial palsy should be evaluated for underlying MRS. Recurrent facial palsy is observed in about 10% of all people with MRS.
Individuals affected by MRS have also reported additional symptoms that include migraines, headaches, tinnitus or sudden deafness, dizziness, dry mouth, facial pain, difficulty swallowing, dry eyes, blurred vision, diarrhea, and excessive tearing. Non-neurological symptoms of MRS may also include inflammation of the intestines (diverticulitis) and inflammation of the eyes (uveitis).
The cause of MRS is still not known. Some cases of MRS have been attributed with various infections by bacterial or viral agents; it is possible that infection with herpesviruses may be a possible cause for MRS. Dietary and other allergens may also be involved in the development of MRS. Some studies have demonstrated the role of hormonal changes triggering the onset of inflammatory episodes. It is also suspected that MRS may be a secondary symptom of another condition such as Crohn’s disease or sarcoidosis. However, no strong associations exist to explain what causes MRS.
There is evidence to suggest that MRS may be inherited because familial inheritance was observed in several patients. However, the presentation of symptoms is highly variable, which makes diagnosis and observing inheritance challenging. While genetics is suspected to be involved, changes (mutations) in specific genes have not been shown to cause the condition. Some reports have implicated several genes to be associated with MRS, but the majority of literature demonstrates that this condition is both clinically and genetically variable.
MRS affects individuals of all ages. Typically, onset of symptoms begins in young adulthood but can occur well into adulthood. While it is not common, a few patients have been diagnosed during childhood. Most literature suggests that MRS tends to affect more females than males. Due to the rarity of MRS, accurate data regarding the incidence of this condition is difficult to obtain. It is likely an under-diagnosed condition as many people with MRS are misdiagnosed because the clinical symptoms overlap with many other common conditions.
MRS is diagnosed clinically, based on physical findings and medical history. The presence of persistent or recurrent facial swelling and either facial palsy or tongue findings may be sufficient for a clinical diagnosis. A biopsy of the lips may be necessary to confirm the diagnosis and rule out possible infectious causes, recurrent angioedema, Crohn’s disease, sarcoidosis or cancers. The presence of only one of the clinical features is enough for diagnosis when a biopsy of affected tissues is consistent with MRS. Because of the overlapping features of MRS with other common conditions, time to diagnosis may take years.
Clinical Testing and Work-Up
The symptoms of MRShave significant overlap with common conditions and initial evaluation may involve specialized laboratory studies and procedures to rule out Crohn’s disease and sarcoidosis. When there is a suspected diagnosis of MRS, it is recommended to follow up with dermatology, immunology, gastroenterology, and ophthalmology to rule out other conditions with similar clinical presentations.
There is no standard method of treatment for MRS. Most signs and symptoms of MRS resolve without treatment but episodes may occur more often and last longer if the condition is not treated. Treatment for MRS may include corticosteroid injections, nonsteroidal anti-inflammatory agents, antihistamines, and antibiotics. In some patients, MRS may be treated with short courses of immunosuppressants. Surgery and/or radiation are sometimes recommended to reduce abnormally swollen lips. If patients experience persistent and recurrent facial paralysis, surgery may be required to decompress affected facial nerves.
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