Carrier Female (XLMTM) Pregnancy Screening

Signs and symptoms of being a ‘manifesting’ x-linked myotubular myopathy (XLMTM) female carrier and considerations for family planning…

Since I was a child I’ve been having lots of muscle weakness symptoms but didn’t really think too much about it. In fact both my parents are professional athletes, and couldn’t understand why their child – me – was so bad at anything sporty! But having my son Noah was like turning on a light switch. He was diagnosed with x-linked myotubular myopathy (XLMTM) and I was confirmed as a carrier mother, meaning that I had passed the defective MTM1 gene onto Noah. The MTM1 gene was a ‘de novo’ mutation in me (or new genetic mutation), in other words my mother didn’t have it. Some female carriers do not present with any muscle weakness symptoms themselves at all, but some will do – with the reasons for this still being discovered*. Now I knew why I had had all those symptoms of mild muscle weakness growing up, and not being sporty like my parents made much more sense.

After the diagnosis of both Noah and me, I kept the genetic reports safe in a file. I remember another mum wisely telling me to do this and how right she was about that – because it came in handy just recently.

Sadly at just 9 months of age, Noah died suddenly and without much warning, of hepatic peliosis (cysts in the liver). There was nothing that we could do about it at the time, and it is incredibly rare so we couldn’t even have predicted it. Even though the conditions are associated with some liver complications.

Noah’s consultant Dr Madhu was amazing during the whole 9 months of Noah’s life – really taking an interest in Myotubular Myopathy (XLMTM). Initially when Noah was first diagnosed, Dr Madhu insisted that I see someone too, as he had noticed that I have muscle weakness symptoms. For example, he spotted that when Noah was very young – and before diagnosis – that I would struggle to stand from a sitting position. We even joked one day that Noah slept with his eyes open, which I had also done so from a child. Dr Madhu was quick to point out to me that this is a strong sign of a neurological problem and urged me to see a neurologist.

The referral

Having Noah, and needing to spend so much of my time to dedicate to him and his care, meant that I needed to put my own symptoms of weakness second, so I didn’t pursue seeking a referral for myself. When Noah passed, I knew that it was something I needed to get sorted. Dr Madhu had kindly put on a note on Noah’s discharge report from hospital for my GP saying ‘Mum needs to go and see a Neuromuscular Specialist’.

So my experience was quite positive around getting a referral and very quickly too. I rang the GP and went over my symptoms, saying that I had some muscle weakness; any anti-gravity movement was tricky, like walking upstairs and picking things up and getting up to standing was a struggle. I have mild anxiety about being stuck in a toilet when going out, for example, not being able to get up to standing again. My left side seems to be worse than the other side. I think because I’d had Noah, this pushed me to get a proper clinical review for myself.

Before I went to see the Neuromuscular Specialist I spoke to a Genetics Consultant. This is because I wish to pursue another pregnancy in the future and needed an NHS referral so that I can get the correct screening throughout the pregnancy. However, when speaking to the geneticist he brought up my mild symptoms of muscle weakness and disagreed that I might be affected, saying ‘there is no way you can have symptoms because my non affected chromosome should work efficiently’! Thankfully, I knew enough about XLMTM and carrier female status from a brilliant webinar provided by the Myotubular Trust, so I knew that I wouldn’t accept this view, I would not be fobbed off. It seemed that the geneticist didn’t understand the connection. So I managed to locate and send him a copy of the genetic report to prove it – something he struggled to even be able to find on Noah’s or my medical records. This is why it is crucial that you keep your genetic report safe, and I know that having it available quickly has saved a lot of time and prevented me from probably having to get it redone.

The appointment

My appointment quickly came up at the local specialist neuromuscular centre. It felt bittersweet going there, and took me back to the time when we first had Noah’s diagnosis. I felt quite prepared for the clinical appointment because I feel that I am well informed – having picked lots of ‘brains’ about XLMTM over the previous year since having Noah, and researching the condition.

What was really helpful though was that the Neuromuscular doctor was clearly an expert and knew about my son’s condition and how it could impact me as a carrier. He referenced the Myotubular Trust’s website for latest papers and he told me I was ‘spot on for a myopathy patient with ‘x-link’. It was a relief to have this confirmed. He told me a lot of times patients like me will manifest strength issues close to the torso – shoulders, hips, upper legs. Because information about strength testing and logging for manifesting female carriers of x-linked Myotubular Myopathy isn’t fully available yet, he based the tests on the ones they use for female carriers of Duchenne muscular dystrophy. He said that to date there is no ‘formal’ diagnosis for x-linked Myotubular Myopathy carrier females so they call it “Genetic Myopathy” and if needed in the future he would have to write a letter if I needed that for any medical insurance.

He agreed that now I was ‘in the system’ I should be regularly screened for – heart, lungs, liver and muscle tone. And he recommended that exercise – just gently – could be helpful to me too and referred me to a physiotherapist. I have started a few exercises myself since the appointment and have noticed how much it helps.

What was great was that he was very up to date with information about the new trials emerging for patients with Myotubular and Centronuclear Myopathy* (*2021) saying that as a carrier female I might be eligible to join one if I so wished. However, I am keen to have more children and that is my priority for the moment.

The pregnancy planning advise for me, as a carrier female of XLMTM

I have felt nervous about the prospect of a new pregnancy and the effect it might have on my muscle strength. What seemed to happen for me when I was pregnant with Noah was that my symptoms seemed to be slightly better and then became worse after birth. Unfortunately my muscle weakness hasn’t improved since birth but has stayed the same.

In terms of pregnancy planning, my husband and I have decided we want other children. We lost our sole purpose in life when we lost our beautiful son Noah and it’s hard not being a mother anymore. I never expected my life without children.

I knew that the input from the NHS takes time from the past experience, so even though it is early after losing Noah, I felt that I wanted to start the ball rolling again. For example, having had IVF to conceive Noah, I knew that it could take about a year to get everything done, from accepted referrals and NHS funding being authorised.

For family’s who are genetic carriers it’s important to have a close relationship with the genetic consultants about family planning. He discussed all the information with me, and about how it could work to be screened for XLMTM in future children. He said we could opt for a natural pregnancy and have a 6 week blood test or a 10 week screening amniocentesis (amnio) test. And then if I was a carrier I could decide if I wanted to keep the pregnancy. I knew that having a termination would be difficult for me to bear, but that is my personal choice. It was great to have an option which suited me as an individual. It was good that the genetic consultant was non-judgemental about any of this and completely supported me with whatever I wanted. So I decided to go through PGD testing again. I’ve already got IVF eggs waiting so half the job is already done.

So now we am looking forward to things started. In the meantime, I am continuing with my gentle exercise and have looked at taking multivitamins – Magnesium and Co-Enzyme Q10 to help detoxify my muscles. I am also exploring other things that work for some children with XLMTM like taking pyridostigmine (mestinon) to see if that would be helpful to me provided it isn’t a toxicity risk during any pregnancy.

At the moment, everything feels positive. And I am so glad that I sought out a Neuromuscular specialist who could help me with my choices knowing about how XLMTM affects my muscle strength. It has made all the difference about how I feel, and wish to approach my future, and most importantly about how I will be supported through my future pregnancy.

by Kate Storey, Noah’s mummy

(2021)