Abstracts

Rationale: Restless Genital Syndrome (RGS) is a rare disorder of unknown etiology, characterized as an excessive, unpleasant genital sensation in the absence of a conscious sexual desire. Paramyotonia congenitais a rare autosomal dominant genetic disorder sometimes caused by SCN4A gene mutations, manifesting with intermittent myotonia and periods of flaccid paralysis. We present a case of RGS in a patient initially diagnosed with partial seizures who was subsequently found to have a mutation in the SCN4A gene.  Methods: case review of a proband with clinical manifestations of RGS, carrying misdiagnosis of partial seizures, found to have a pathogenic SCN4A mutation Results: A teen male was diagnosed with “atypical” partial seizures. Initial symptoms were sudden nocturnal onset of genital hyperesthesia with a mix of burning, tingling, and throbbing pain, without erection or sexual interest.  The patient could not wear pajamas due to the discomfort, and he slept on his back with a box over his naked perineum to prevent blankets from touching him. Occasionally the symptoms were followed by an inability to move his legs, or with confusion and an inability to speak fluently.  When day events commenced, he avoided all educational, social, and recreational activities.  EEG and EMG were unrevealing.  He was treated with anticonvulsants, other medications, and psychological counseling, with no benefit. Reanalysis of the semiology led to a clinical diagnosis of RGS.  However, because his episodes of periodic paraplegia did not fit prior descriptions of RGS, and because his mother had episodes of paroxysmal dystonia, genetic tests for periodic paralyses and dystonia were sent. Results revealed a presumed pathogenic missense mutation in exon 24 (Arg1448Cys) of the sodium channel SCN4A associated with paramyotonia congenita. All the patient’s sensory and motor symptoms resolved completely after treatment with hydrochlorothiazide, and he returned to school. Treating his mother with hydrochlorothiazide resolved her paroxysmal dystonia. Conclusions: RGS, described in 2009, is associated with Restless Legs Syndrome, overactive bladder, urethral hypersensitivity, and genital dysesthesia/allodynia.  The first cases were attributed to a pudendal small fiber neuropathy exacerbated by pelvic varices of middle aged women.  Rare cases in adult males have been described. Treatments with the antiandrogen leuprolide, antidepressants, varenicline, benzodiazepines, anesthetic gels, transcutaneous electrical nerve stimulation, clitoridectomy, electroconvulsive therapy, and cognitive behavioral therapy have had unsatisfactory results. Treatment of our patient with hydrochlorothiazide, which competes for the chloride site of a sodium chloride co-transporter, resolved all our patient’s symptoms completely.  Although this is standard treatment of paramyotonia congenita associated with SCN4A mutations a search revealed no reports of it in RGS, nor of cases of RGS associated with SCN4A mutations.  Our findings raise the possibility that some cases of RGS may be caused by SCN4A mutations, and highlight the utility of semiology as a guide to focused molecular diagnosis and treatment.  Funding: None