Melkersson-Rosenthal Syndrome and Migraine: A New Phenotype Associated with SCN1A Variants?

Peripheral facial palsy rarely occurs as part of Melkersson-Rosenthal syndrome (MRS), which is characterized by the classical triad of tongue cheilitis, recurrent episodes of orofacial swelling, and palsy. MRS is a disorder with variable expressivity and clinical as well as genetic heterogeneity; however, the causative gene remains to be identified. Migraine is a common neurological disorder, presenting with or without aura, which may be associated with neurological symptoms. The classical example of monogenic migraine is familial hemiplegic migraine (FHM), which has phenotypic variability in carriers of variants in the same gene or even carriers of the same variant. We present a family in which two sisters displayed recurrent migraines, one of which presented recurrent facial palsy and had clinical diagnosis of MRS. We performed WES and Sanger sequencing for segregation analysis in the available family members. We identified a c.3521C>G missense heterozygous variant in SCN1A carried only by the affected sister. Variants in the SCN1A gene can cause a spectrum of early-onset epileptic encephalopathies, in addition to FHM; therefore, our finding reasonably explains the proband phenotype, in which the main symptom was recurrent facial palsy. This report also adds knowledge to the clinical spectrum of SCN1A alterations and suggests a potential overlap between MRS and FHM.

A case-control study of HLA alleles in Brazilian patients with Melkersson-Rosenthal syndrome.

Melkersson-Rosenthal syndrome (MRS) is a neuromucocutaneous disease that manifests by the triad of recurrent orofacial edema (frequently as cheilitis granulomatosa), relapsing facial paralysis and plicated tongue. The cause of MRS remains unknown, but genetic predisposal and a relationship with inflammatory bowel disease are suspected. The objective of this research was to compare the frequency of class I and II HLA alleles in patients with a confirmed diagnosis of MRS with those of a healthy control group. We conduct a case-control study and typed of HLA A, B, C, DR, and DQ using molecular techniques. The study included 36 patients with MRS and 297 patients in the control group. There was an increase in the expression of HLA A*02 (p = 0.0269; OR: 1,79 [1,045-2,973]), HLA DRB1*11 (p < 0,0001; OR: 4,009 [2,214-7,277]), HLA DRB1*13 (not statistically significant) and HLA DQB1*03 (p = 0,0177; OR: 1,829 [1,122-2,978]) and low levels of HLA A*01 (p = 0.0046; OR: 0,097 [0,009-0,538]), HLA DRB1*04 (p = 0.0274; OR: 0,228 [0,053-0,844]), HLA DRB1*07 (p = 0,0091; OR: 0,183 [0,043-0,670]) and HLA DQB1*02 (p = 0.0051; OR: 0,312 [0,143-0,721]) in MRS patients compared with the control group. Crohn disease (CD) patients had disparate genetic profiles versus those with MRS. This single-institution study had a small cohort, because this disease is rare. Conclusions: There is a genetic predisposition toward MRS, involving associated and protective genes.

Melkersson-Rosenthal syndrome: About a Tunisian family and review of the literature.

Melkersson-Rosenthal (MRS) syndrome is a rare disorder defined as a triad of recurrent peripheral facial palsy, orofacial edema, and fissured tongue. The etiology of this disease is still unclear. Genetic origin has been postulated. Several theories have been advanced to provide further evidence for a hereditary basis of MRS. We describe a case of 14-year-old girl presented with the classic triad symptoms of MRS. The diagnosis of MRS was made on the basis of history, clinical, histopathological examinations and exclusion of differential diagnosis. The family history showed that some members presented similar symptoms. A chromosome analysis was performed. This observation with familial occurrence of MRS may support the genetic origin theory of MRS. However; present available studies do not provide sufficient evidence to confirm a genetic origin.

Clinical and genetic heterogeneity in Melkersson-Rosenthal Syndrome.

Melkersson Rosenthal syndromes (MRS) is a rare autosomal dominantly inherited neurocutaneous syndrome characterised by a triad of facial (seventh cranial) nerve palsy, recurrent orofacial swelling and fissuring of the tongue. A recent report implicated a heterozygous missense variant in SLC27A1 (FATP1) as the cause of this condition in members of an affected Chinese family. We undertook Sanger sequencing of this gene in 14 affected unrelated individuals affected by MRS. We did not detect any putative pathogenic variants. Our data indicates that there is both clinical and genetic heterogeneity in this condition and that the causative gene remains to be identified for the majority of cases.

Facial palsy in Melkersson-Rosenthal syndrome and Bell's palsy: familial history and recurrence tendency.

OBJECTIVE: The aim of this study was to compare genetic predilection and recurrence tendency between facial palsy in Melkersson-Rosenthal syndrome (MRS) and Bell's palsy METHODS: We carried out an investigation on patients with facial palsy in MRS and those with Bell's palsy who visited the outpatient department in our hospital between February 2009 and February 2013. They were asked about familial history and whether it was the first episode, with the results recorded and compared. RESULTS: There were 16 patients with facial palsy in MRS and 860 patients with Bell's palsy involved in the study. Familial history was positive in 5 of 16 patients (31.3%) with facial palsy in MRS and 56 of 860 patients (6.5%) with Bell's palsy (P < .01). Twelve of 16 cases (75%) with facial palsy in MRS and 88 of 860 cases (10.2%) with Bell's palsy had a history of facial palsy in the past (P < .01). CONCLUSION: Compared to Bell's palsy, facial palsy in MRS has an obvious genetic predilection and recurrence tendency.

Intralymphatic granulomas as a pathogenic factor in cheilitis granulomatosa/Melkersson-Rosenthal syndrome: report of a case with immunohistochemical and molecular studies.

Orofacial granulomatosis, an uncommon immunologically mediated disorder, includes cheilitis granulomatosa and Melkersson-Rosenthal syndrome. It is clinically characterized by recurrent or persistent swelling of the orofacial tissues with a spectrum of other orofacial features and sometimes with neurological symptoms. The pathological findings are varied but are often characterized by the presence of noncaseating granuloma. We present a new case of orofacial granulomatosis with unusual histopathological findings, namely, intralymphatic granulomas. These may be the cause of the tissue edema. We demonstrated, by immunohistochemical studies, the lymphatic nature of the vessels affected by the granulomatous process.

Hereditary Melkersson-Rosenthal syndrome and multiple sclerosis.

UNLABELLED: The revision of MEDLINE from 1966 to 2003 did not report any association between multiple sclerosis (MS) and Melkersson-Rosenthal syndrome (MRS). This is a case report of a 51-year-old woman, with history of four recurrent Bell's palsies. In 1999 she developed a right facial paralysis due to a supranuclear pyramidal lesion with right monoparesis. The family history showed five relatives with recurrent Bell's paralysis and plicata tongue. PHYSICAL EXAMINATION: right Bell's paralysis, left supranuclear facial paralysis, furrowed tongue, right hemiparesis with pallor of the optic disks. Brain magnetic resonance imaging (MRI) demonstrated the typical lesions of MS and CSF oligoclonal bands. This is the first observation of a patient with hereditary MRS and MS. The link between both diseases is discussed.

Non-specific influx of T-cell receptor alpha/beta and gamma/delta lymphocytes in mucosal biopsies from a patient with orofacial granulomatosis.

Orofacial granulomatosis (OFG) represents an inflammatory disorder of the facial and oral mucosa, histologically characterized by non-caseating epithelioid cell granulomas. Since other granulomatous diseases have been shown to be characterized by a limited heterogeneity of alpha/beta and gamma/delta T cells, we investigated the T-cell diversity of both types of lymphocytes obtained from the same OFG patient. When we compared the T-cell receptor diversity of the lymphocytes accumulating at the site of the lesions with that of the peripheral blood counterpart, we did not find significant differences. Furthermore, no exclusive expansions of different T-cell clones were seen in the patient. From these data we conclude that, in this OFG patient, the majority of T cells have no specificity for a single or for a few antigens and that tissue accumulation of T lymphocytes is the result of a random influx of cells at the site of inflammation.

[A case of typical Melkersson-Rosenthal syndrome with possible autosomal dominant inheritance].

Here we presented a case of 40-year-old woman who suffered from bilateral facial palsy and headache. She had allegedly had an episode of facial palsy, and facial edema at her age of 14 years. Physical examination revealed swelling of the lips, upward disturbance of the left eye, hypogeusia, the fissured tongue, and bilateral facial palsy. Oral administration of prednisolone 20 mg/day yielded gradual but complete improvement of the facial palsy and hypogeusia within two weeks. Careful analysis of family history disclosed that four members had oro-facio-cervical edema and three had the fissured tongue. A diagnosis of Melkersson-Rosenthal syndrome with possible autosomal dominant inheritance was made based on the clinical findings and familial aggregation of the incomplete form of this syndrome.

Síndrome de melkersson rosenthal

El sindrome de Melkersson Rosenthal consiste en edema recurrente de los labios, parálisis facial intermitente y lengua escrotal. Fue descrito a principios de siglo en Zuiza y la mayor parte de los casos reportados provienen de Europa, pero en la actualidad hay información de pacientes de los cinco continentes. Se describe el caso de una paciente de 53 años que consultó por edema recurrente del labio superior de tres años de evolución que no ha respondido a glucocorticoides, ni antihistaminicos. En la anamnesia se encontró que había tenido parálisis facial derecha hace ocho años, y hace un año neuritis de la rama maxilar izquierda del nervio trigémino. En el examen físico se destaca el edema blando no doloroso localizado en el lado dercho del labio superior y lengua escrotal (plicata). Como patologías asociadas refiere diabetes mellitus controlada con dieta e hipertensión arterial en tratamiento con captopril. Los análisis de laboratorio no muestran alteraciones importantes, salvo la elevación de la glicemia y la biopsia labial muestra cambios inflamatorios crónicos

Molecular analysis of T cell receptor beta variability in a patient with orofacial granulomatosis.

BACKGROUND: Orofacial granulomatosis (OFG) is a rare chronic inflammatory disorder of unknown causation and is characterised histologically by non-caseating granulomas and aggregates of small lymphocytes. The molecular nature of these T cells is, however, unclear. AIMS: To determine the T cell receptor (TCR) V beta gene usage of the T cell infiltrate associated with the primary lesions in a patient with OFG. METHODS: A molecular method involving reverse transcriptase (RT)-polymerase chain reaction (PCR), DNA cloning, single strand conformation polymorphism (SSCP), length analysis, and nucleotide sequencing was used. RESULTS: Compared with peripheral blood lymphocytes from the same patient, notably restricted TCRV beta gene usage was observed in the T cell infiltrate. Only three of the 24 major TCRV beta gene families were represented in the repertoire. There was preferential usage of the V beta 6 gene. In addition, more than 20% of the V beta 6 TCR transcripts exhibited an identical unique V-D-J junctional sequence, suggesting a local antigen driven V beta 6 T cell clonal expansion in vivo, a phenomenon not observed in normal oral mucosa. CONCLUSIONS: The TCRV beta repertoire of T cells associated with OFG is restricted. It is also associated with a local T cell clonal expansion. The results, therefore, provide a new perspective on the immunopathology of OFG.

Melkersson-Rosenthal syndrome and de novo autosomal t(9;21)(p11;p11) translocation.

In this report we describe a 26-year-old female with the typical clinical symptoms and signs of Melkersson-Rosenthal syndrome, an autosomal dominant with variable expression, and a de novo t(9;21)(p11;p11), and suggest that the "Melkersson-Rosenthal gene" is located at 9p11.

Melkersson-Rosenthal syndrome.

Melkersson-Rosenthal syndrome is a rare condition, classically associated with a triad of facial and/or lip edema, fissured tongue, and relapsing facial palsy. This article offers a review of the literature and presents two cases of Melkersson-Rosenthal syndrome associated with elevated serum levels of angiotensin converting enzyme in two patients of Thai descent.

[Melkersson-Rosenthal syndrome in Curschmann-Steinert dystrophia myotonica]. / Melkersson-Rosenthal-Syndrom bei Dystrophia myotonica Curschmann-Steinert.

We report the case of a 52-year-old female patient who suffered both from myotonic dystrophy (Curschmann-Steinert disease) and Melkersson-Rosenthal syndrome. Both syndromes showed the full-blown clinical features as well as the typical histology. In addition to the possibility that the appearance of the two syndromes together was a mere coincidence, we also consider the possibility that there was a hereditary diencephalic disorder present that linked together some of the minor manifestations of both syndromes.