BEUDAMED
    FDA Adverse Event Injury Summary report: N

    UNKNOWN IMPLANTABLE NEUROSTIMULATOR

    MDR report key: 8796161 · Received July 16, 2019

    Report

    Report Number
    3007566237-2019-01576
    Event Type
    Injury
    Date Received
    July 16, 2019
    Date of Event
    June 5, 2019
    Report Date
    July 16, 2019
    Manufacturer
    MEDTRONIC NEUROMODULATION
    Product Code
    MRU
    PMA / PMN Number
    H020007
    Adverse Event
    Yes
    Product Problem
    Yes
    Report Source
    Manufacturer report
    Reporter Location
    GM
    Reporter Occupation
    PHYSICIAN

    Narratives

    Additional Manufacturer Narrative · 1

    DAFSAR, H.S., SPRUTE, R., WUNDERLICH, G., DAIMAGULER, H-S., KARACA, E., CONTRERAS, A., BECKER, K., SCHULZE-RHONHOF, M., KIENING, K., KARAKULAK, T., KLOSS, M., HORN, A., PAULS, A., NURNBERG, P., ALTMULLER, J., THIELE, H., ASSMANN, B., KOY, A., CIRAK, S. NOVEL MUTATIONS IN KMT2B OFFER PATHOPHYSIOLOGICAL INSIGHTS INTO CHILDHOOD-ONSET PROGRESSIVE DYSTONIA. JOURNAL OF HUMAN GENETICS. 2019. DOI: 10.1038/S10038-019-0625-1. DATE OF EVENT: PLEASE NOTE THAT THIS DATE IS BASED OFF OF THE DATE OF PUBLICATION OF THE ARTICLE AS THE EVENT DATES WERE NOT PROVIDED IN THE PUBLISHED LITERATURE. CONCOMITANT MEDICAL PRODUCTS: PRODUCT ID: NEU_UNKNOWN_LEAD, SERIAL #: UNKNOWN, PRODUCT TYPE: LEAD. OTHER RELEVANT DEVICE(S) ARE: PRODUCT ID: NEU_UNKNOWN_LEAD, SERIAL/LOT #: UNKNOWN, UDI #: ASKU. IF INFORMATION IS PROVIDED IN THE FUTURE, A SUPPLEMENTAL REPORT WILL BE ISSUED.

    Description of Event or Problem · 1

    SUMMARY: RAPID PROGRESS HAS RECENTLY BEEN MADE IN THE ELUCIDATION OF THE GENETIC BASIS OF CHILDHOOD-ONSET INHERITED GENERALIZED DYSTONIA (IGD) DUE TO THE IMPLEMENTATION OF GENOMIC SEQUENCING METHODOLOGIES. THE AUTHORS IDENTIFIED FOUR PATIENTS WITH CHILDHOOD-ONSET IGD HARBORING NOVEL DISEASE-CAUSING MUTATIONS IN LYSINE-SPECIFIC HISTONE METHYLTRANSFERASE 2B GENE (KMT2B) BY WHOLE-EXOME SEQUENCING. THE MAIN FOCUS OF THIS PAPER IS TO GAIN NOVEL PATHOPHYSIOLOGICAL INSIGHTS THROUGH UNDERSTANDING THE MOLECULAR CONSEQUENCES OF THESE MUTATIONS. THE DISEASE COURSE IS MOSTLY PROGRESSIVE, EVOLVING FROM LOWER LIMBS INTO GENERALIZED DYSTONIA, WHICH COULD BE ASSOCIATED WITH DYSARTHRIA, DYSPHONIA, INTELLECTUAL DISABILITY, OROFACIAL DYSKINESIA, AND SOMETIMES DISTINCT DYSMORPHIC FACIAL FEATURES. IN TWO PATIENTS, MOTOR PERFORMANCES IMPROVED AFTER BILATERAL IMPLANTATION OF DEEP BRAIN STIMULATION IN THE GLOBUS PALLIDUS INTERNUS (GPI-DBS). PHARMACOTHERAPY WITH TRIHEXYPHENIDYL REDUCED DYSTONIA IN TWO PATIENTS. THE AUTHORS DISCOVERED THREE NOVEL KMT2B MUTATIONS. THE AUTHORS' ANALYSES REVEALED THAT THE MUTATION IN PATIENT 1 (C.7463A > G, P.Y2488C) IS LOCALIZED IN THE HIGHLY CONSERVED FYRC DOMAIN OF KMT2B. THIS MUTATION HOLDS THE POTENTIAL TO ALTER THE INTER-DOMAIN FYR INTERACTIONS, WHICH COULD LEAD TO KMT2B INSTABILITY. THE MUTATIONS IN PATIENTS 2 AND 3 (C.3596_3697INSC, P.M1202DFS*22; C.4229DELA, P.Q1410RFS*12) LEAD TO PREDICTED UNSTABLE TRANSCRIPTS, LIKELY TO BE SUBJECT TO DEGRADATION BY NON-SENSE-MEDIATED DECAY. CHILDHOOD-ONSET PROGRESSIVE DYSTONIA WITH OROFACIAL INVOLVEMENT IS ONE OF THE MAIN CLINICAL MANIFESTATIONS OF KMT2B MUTATIONS. IN ALL, 26% (18/69) OF THE REPORTED CASES HAVET2 SIGNAL ALTERATIONS OF THE GLOBUS PALLIDUS INTERNUS, MOSTLY AT A YOUNGER AGE. ANTICHOLINERGIC MEDICATION AND GPI-DBS ARE PROMISING TREATMENT OPTIONS AND SHALL BE CONSIDERED EARLY. REPORTED EVENT: PATIENT 1: A (B)(6) FEMALE PATIENT WITH BILATERAL DEEP BRAIN STIMULATION (DBS) OF THE INTERNAL GLOBUS PALLIDUS (GPI) EXPERIENCED SUDDEN DETERIORATION OF DYSTONIC SYMPTOMS AND DYSARTHRIA. BOTH LEADS WERE REPLACED AND THE PATIENT'S SYMPTOMS PROMPTLY IMPROVED. NO DEVICE SPECIFICS COULD BE IDENTIFIED FROM THE PUBLISHED LITERATURE ARTICLE.

    Devices

    Seq Brand Generic Product Code Manufacturer Model Lot UDI-DI
    588399 UNKNOWN IMPLANTABLE NEUROSTIMULATOR IMPLANTED SUBCORTICAL ELECTRICAL STIMULATOR (MOTOR DISORDERS) MRU MEDTRONIC NEUROMODULATION NEU_INS_STIMULATOR

    Patients

    Seq Age Sex Outcome Treatment
    1 10 YR Required Intervention