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Melkersson-Rosenthal Syndrome and Migraine: A New Phenotype Associated with SCN1A Variants?
Alessia Azzarà1, Ilaria Cassano1, Carla Lintas1,2
1Research Unit of Medical Genetics, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy.
Abstract:
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.
Insights
Melkersson-Rosenthal syndrome (MRS) is rare, but a new study links facial palsy in one patient to a SCN1A gene variant. This finding suggests a potential overlap between MRS and familial hemiplegic migraine (FHM).
Area of Science:
- Genetics and Neurology
- Rare disease research
Background:
- Melkersson-Rosenthal syndrome (MRS) is a rare disorder characterized by facial palsy, orofacial swelling, and tongue cheilitis, with an unidentified genetic cause.
- Familial hemiplegic migraine (FHM) is a subtype of migraine linked to specific gene variants, exhibiting significant phenotypic variability.
Purpose of the Study:
- To investigate the genetic basis of recurrent migraines and facial palsy in a family with a clinical diagnosis of MRS.
- To explore potential genetic links between MRS and FHM.
Main Methods:
- Whole Exome Sequencing (WES) was performed on family members.
- Sanger sequencing was used for segregation analysis of identified variants.
- Clinical data from affected individuals was reviewed.
Main Results:
- A heterozygous missense variant (c.3521C>G) in the SCN1A gene was identified exclusively in the affected sister.
- This SCN1A variant is known to be associated with early-onset epileptic encephalopathies and FHM.
- The proband's primary symptom of recurrent facial palsy is consistent with the known neurological effects of SCN1A variants.
Conclusions:
- The identified SCN1A variant provides a potential genetic explanation for the proband's phenotype, including recurrent facial palsy.
- This finding expands the known clinical spectrum of SCN1A alterations.
- The study suggests a possible genetic overlap between Melkersson-Rosenthal syndrome and familial hemiplegic migraine.
