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Obstetric and gynaecological features in females carrying variants in the skeletal muscle ryanodine receptor (RYR1) gene: a questionnaire study
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  • Arti Mistry,
  • Georgia Saldanha,
  • Luuk van den Bersselaar R,
  • Greg A. Knock,
  • Michael Goldberg F,
  • Maria Vanegas I,
  • Miguel Fernandez-Garcia A,
  • Susan Treves,
  • Nicol Voermans C,
  • Rachel Tribe,
  • Heinz Jungbluth
Arti Mistry
King's College London School of Life Course & Population Sciences
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Georgia Saldanha
King's College London School of Life Course & Population Sciences
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Luuk van den Bersselaar R
Canisius Wilhelmina Ziekenhuis
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Greg A. Knock
King's College London School of Immunology & Microbial Sciences
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Michael Goldberg F
RYR 1 Foundation
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Maria Vanegas I
Evelina London Children's Hospital Paediatrics
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Miguel Fernandez-Garcia A
Evelina London Children's Hospital Paediatrics
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Susan Treves
Universitat Basel Departement Biomedizin
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Nicol Voermans C
Radboudumc Afdeling Neurologie
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Rachel Tribe
King's College London School of Life Course & Population Sciences
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Heinz Jungbluth
Evelina London Children's Hospital Paediatrics

Corresponding Author:[email protected]

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Abstract

Objective: To assess the impact of skeletal muscle ryanodine receptor ( RYR1) variants, a common cause of neuromuscular disorders, on smooth muscle function, bleeding, obstetric, and gynaecological outcomes. Design: Questionnaire study. Setting: Online via the RYR1-Foundation patient support group covering countries across the world. Population or Sample: 154 women consisting of 66 RYR1-variant carrying participants and 88 controls. Methods: Online questionnaire designed to investigate symptoms of abnormal smooth muscle function, obstetric and gynaecological outcomes in women with RYR1 variants. Questions were developed using a modified version of the MCMDM-1VWD questionnaire, and the NHS-heavy periods self-assessment tool. Obstetric and gynaecological symptoms explored include pregnancy-related complications, gestation length, parturition duration, post-partum haemorrhage and offspring birthweight. Main Outcome Measures: Bleeding scores were measured using a modified MCMDM-1VWD scale. Significance between groups were analysed using Fisher exact tests, Chi Square tests, and Welch’s t-tests. Results: Women with RYR1 variants exhibited a higher incidence of pathological bleeding scores (p<0.0001), severe menstrual bleeding, complications during pregnancy (preeclampsia and placenta praevia), post-partum haemorrhage, shorter pregnancies, frequent planned Caesarean sections, and offspring with lower birthweight, compared to controls. Gastrointestinal symptoms were also more common. Conclusions: RYR1 mutated females exhibit a bleeding disorder and frequent gynaecological and obstetric complications. Considering their population frequency in otherwise pauci-symptomatic individuals, RYR1 variants ought to be considered as a cause of otherwise unexplained menorrhagia and other gynaecological and obstetric manifestations. Funding: King’s Health Partners Institute of Women and Children’s Health Keywords: skeletal muscle ryanodine receptor (RYR1) gene; questionnaire; bleeding; menorrhagia; post-partum haemorrhage Tweetable abstract: RYR1 mutated females exhibit a bleeding disorder. RYR1 variants ought to be considered as a cause of otherwise unexplained menorrhagia, PPH and obstetric complications.