Clinical,pathological And Genetic Analysis Of Patients With Family Episodic Pain Syndrome

Background:Family episodic pain syndrome(FEPS)is a rare genetic disease caused by mutations in ion channel genes.Its clinical characteristics are severe paroxysmal pain in early childhood,mainly affecting the distal extremities.In clinical practice,many doctors have insufficient understanding of it,often leading to missed or misdiagnosed diagnosis.Therefore,this study aims to deepen clinicians’ understanding of this disease by retrospectively analyzing the clinical manifestations,peripheral neuropathic changes,and gene mutation characteristics of a group of FEPS patients.Methods:This study included FEPS patients diagnosed at the First Affiliated Hospital of Nanchang University and the People’s Hospital of Peking University from January2018 to December 2022.Obtain detailed medical history information from the patient and their relatives,including the patient’s age of onset,trigger factors,disease progression,family history,and other relevant medical history information.Two of the patients underwent sural nerve biopsies and related pathological examinations,and all patients underwent full exon sequencing.Results:1.A total of 25 patients were included in this study,including 9 sporadic patients and 16 patients from 2 autosomal dominant families.Of the 25 patients with FEPS,13(52%)were male and 12(48%)were female,with an average age of 30.2 ± 18.5years.The main initial symptoms of patients are paroxysmal limb pain and numbness,mostly in both lower limbs,knees,and ankles.Sometimes the pain moves upward to the elbows,wrists,and palms,and occasionally affects the proximal limbs and waist.2.Physical and laboratory examinations of all patients during the interval between pain episodes showed no significant abnormalities.Two patients from family 1completed nerve biopsy,and no significant abnormalities were observed in the sural nerve of the proband(F1:V1).Furthermore,the ultrastructural results revealed normal myelinated and unmyelinated fiber structures.However,the symptoms of the proband’s father(F1:IV1)disappeared,and a significant decrease in the density of unmyelinated fibers was observed in the nerve biopsy.The electron microscopy further confirmed the loss of unmyelinated fibers and the formation of collagen bags,but no significant abnormalities were observed in the large number of myelinated nerve fibers.3.Exon sequencing revealed that 3 of the 11 probands carried mutations in the SCN11 A gene,while the other 8 patients did not detect phenotypically related or suspected pathogenic mutations.Family 1 patient carries a classic known mutation c.665G>A(p.R222H);A novel heterozygous mutation c.2138T>A(p.F713Y)in the SCN11 A gene was found in family 2 patients;Sporadic patients have a novel mutation of c.2443A>C(p.S815R).Conclusions:1.Neuroelectrophysiology and neural tissue biopsy have no specificity in diagnosing the onset of FEPS,but as symptoms disappear,some patients may develop unmyelinated nerve fiber lesions.This type of examination can help clinicians differentiate FEPS from other types of peripheral neuropathy.2.In the cohort of FEPS patients included in the study,FEPS3 type patients were mainly caused by mutations in the SCN11 A gene,and two possible pathogenic sites of FEPS3 were found in the SCN11 A gene.However,there are still many patients with FEPS who are genetically negative or whose pathogenesis is unknown,which also suggests that there may be some bias in the inclusion of patients in the diagnosis of clinical symptoms alone.