Ryanodine receptor 1 related myasthenia like myopathy responsive to pyridostigmine

Emilie Boye Lester; Martin Jakob Larsen; Lone Walentin Laulund; Niels Illum; Ulrike Dunkhase-Heinl; Henrik Daa Schrøder; Christina Ringmann Fagerberg

doi:10.1016/j.ejmg.2023.104706

Ryanodine receptor 1 related myasthenia like myopathy responsive to pyridostigmine

Emilie Boye Lester, Martin Jakob Larsen, Lone Walentin Laulund, Niels Illum, Ulrike Dunkhase-Heinl, Henrik Daa Schrøder, Christina Ringmann Fagerberg

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Abstract

Disease causing variants in the Ryanodine receptor 1 (RYR1) gene are a common cause for congenital myopathy and for malignant hyperthermia susceptibility. We report a 17 year old boy with congenital muscle weakness progressing to a myasthenia like myopathy with muscle weakness, fatigability, ptosis, and ophthalmoplegia. Muscle biopsy showed predominance and atrophy of type 1 fibers. Whole-exome trio sequencing revealed three variants in the RYR1-gene in the patient: c.6721C > T,p.(Arg2241*) and c.2122G > A,p.(Asp708Asn) in cis position, and the c.325C > T,p.(Arg109Trp) variant in trans. Treatment with pyridostigmine improved symptoms. This case supports that a myasthenia like phenotype is part of the phenotypic spectrum of RYR1 related disorders, and that treatment with pyridostigmine can be beneficial for patients with this phenotype.

Original language	English
Article number	104706
Journal	European Journal of Medical Genetics
Volume	66
Issue number	3
ISSN	1769-7212
DOIs	https://doi.org/10.1016/j.ejmg.2023.104706
Publication status	Published - Mar 2023

Keywords

Malignant hyperthermia
Myasthenia
Ophthalmoplegia
RYR1 congenital myopathy
Ryanodine receptor calcium release channel
Therapeutics
Ryanodine Receptor Calcium Release Channel/genetics
Humans
Muscle Weakness/genetics
Male
Muscle, Skeletal/pathology
Phenotype
Pyridostigmine Bromide/therapeutic use
Adolescent
Mutation
Muscular Diseases/genetics

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10.1016/j.ejmg.2023.104706

Open Access VersionAccepted manuscript, 429 KBLicence: CC BY-NC-ND

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title = "Ryanodine receptor 1 related myasthenia like myopathy responsive to pyridostigmine",

abstract = "Disease causing variants in the Ryanodine receptor 1 (RYR1) gene are a common cause for congenital myopathy and for malignant hyperthermia susceptibility. We report a 17 year old boy with congenital muscle weakness progressing to a myasthenia like myopathy with muscle weakness, fatigability, ptosis, and ophthalmoplegia. Muscle biopsy showed predominance and atrophy of type 1 fibers. Whole-exome trio sequencing revealed three variants in the RYR1-gene in the patient: c.6721C > T,p.(Arg2241*) and c.2122G > A,p.(Asp708Asn) in cis position, and the c.325C > T,p.(Arg109Trp) variant in trans. Treatment with pyridostigmine improved symptoms. This case supports that a myasthenia like phenotype is part of the phenotypic spectrum of RYR1 related disorders, and that treatment with pyridostigmine can be beneficial for patients with this phenotype.",

keywords = "Malignant hyperthermia, Myasthenia, Ophthalmoplegia, RYR1 congenital myopathy, Ryanodine receptor calcium release channel, Therapeutics, Ryanodine Receptor Calcium Release Channel/genetics, Humans, Muscle Weakness/genetics, Male, Muscle, Skeletal/pathology, Phenotype, Pyridostigmine Bromide/therapeutic use, Adolescent, Mutation, Muscular Diseases/genetics",

author = "Lester, {Emilie Boye} and Larsen, {Martin Jakob} and Laulund, {Lone Walentin} and Niels Illum and Ulrike Dunkhase-Heinl and Schr{\o}der, {Henrik Daa} and Fagerberg, {Christina Ringmann}",

note = "Copyright {\textcopyright} 2023. Published by Elsevier Masson SAS.",

year = "2023",

month = mar,

doi = "10.1016/j.ejmg.2023.104706",

language = "English",

volume = "66",

journal = "European Journal of Medical Genetics",

issn = "1769-7212",

publisher = "Elsevier Masson",

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T1 - Ryanodine receptor 1 related myasthenia like myopathy responsive to pyridostigmine

AU - Lester, Emilie Boye

AU - Larsen, Martin Jakob

AU - Laulund, Lone Walentin

AU - Illum, Niels

AU - Dunkhase-Heinl, Ulrike

AU - Schrøder, Henrik Daa

AU - Fagerberg, Christina Ringmann

PY - 2023/3

Y1 - 2023/3

N2 - Disease causing variants in the Ryanodine receptor 1 (RYR1) gene are a common cause for congenital myopathy and for malignant hyperthermia susceptibility. We report a 17 year old boy with congenital muscle weakness progressing to a myasthenia like myopathy with muscle weakness, fatigability, ptosis, and ophthalmoplegia. Muscle biopsy showed predominance and atrophy of type 1 fibers. Whole-exome trio sequencing revealed three variants in the RYR1-gene in the patient: c.6721C > T,p.(Arg2241*) and c.2122G > A,p.(Asp708Asn) in cis position, and the c.325C > T,p.(Arg109Trp) variant in trans. Treatment with pyridostigmine improved symptoms. This case supports that a myasthenia like phenotype is part of the phenotypic spectrum of RYR1 related disorders, and that treatment with pyridostigmine can be beneficial for patients with this phenotype.

AB - Disease causing variants in the Ryanodine receptor 1 (RYR1) gene are a common cause for congenital myopathy and for malignant hyperthermia susceptibility. We report a 17 year old boy with congenital muscle weakness progressing to a myasthenia like myopathy with muscle weakness, fatigability, ptosis, and ophthalmoplegia. Muscle biopsy showed predominance and atrophy of type 1 fibers. Whole-exome trio sequencing revealed three variants in the RYR1-gene in the patient: c.6721C > T,p.(Arg2241*) and c.2122G > A,p.(Asp708Asn) in cis position, and the c.325C > T,p.(Arg109Trp) variant in trans. Treatment with pyridostigmine improved symptoms. This case supports that a myasthenia like phenotype is part of the phenotypic spectrum of RYR1 related disorders, and that treatment with pyridostigmine can be beneficial for patients with this phenotype.

KW - Malignant hyperthermia

KW - Myasthenia

KW - Ophthalmoplegia

KW - RYR1 congenital myopathy

KW - Ryanodine receptor calcium release channel

KW - Therapeutics

KW - Ryanodine Receptor Calcium Release Channel/genetics

KW - Humans

KW - Muscle Weakness/genetics

KW - Male

KW - Muscle, Skeletal/pathology

KW - Phenotype

KW - Pyridostigmine Bromide/therapeutic use

KW - Adolescent

KW - Mutation

KW - Muscular Diseases/genetics

U2 - 10.1016/j.ejmg.2023.104706

DO - 10.1016/j.ejmg.2023.104706

M3 - Journal article

C2 - 36669590

SN - 1769-7212

VL - 66

JO - European Journal of Medical Genetics

JF - European Journal of Medical Genetics

IS - 3

M1 - 104706

ER -

Ryanodine receptor 1 related myasthenia like myopathy responsive to pyridostigmine

Abstract

Keywords

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