Obstetric and gynaecological features in females carrying variants in
the skeletal muscle ryanodine receptor (RYR1) gene: a questionnaire
study
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.