Muscular Dystrophy Genetics, Carriers and Family Testing

Families, carriers and genetics: the relatives nobody follows up

In the Australian study that established the incidence of Duchenne muscular dystrophy in New South Wales and the ACT, the researchers recorded something beyond the incidence figure. They looked at what happened to the families.

Carrier testing was accessed by 116 of 141 eligible first-degree relatives — 82.3 per cent. Only four of 107 mothers declined testing. That is a good result and it reflects well on the clinical genetics services involved.

Counselling was documented for 37 per cent of potential second-degree relatives — 45 of 122.

And 11 of 107 cases, or 10.3 per cent, were classified as theoretically preventable: a diagnosis in a family where an earlier diagnosis in a relative meant the risk could in principle have been known.

That is the shape of the problem. The mother gets tested. The aunt, the cousin, the grandmother’s sister’s daughter — the women who carry the same 50 per cent question and who would want to know before they have children — are told by a family member, or not told at all. Two in three of them have no documented contact with a genetics service.

This guide covers the inheritance patterns by type, what carrier status actually means including the cardiac surveillance that carrier women need and almost never receive, how to make sure relatives are informed, reproductive options, and the family and carer side of living with these conditions.

The inheritance patterns, by type

This is the part worth getting right, because the implications for siblings and children differ completely between types and families are regularly given the wrong framework.

X-linked recessive — Duchenne and Becker muscular dystrophy. The gene is on the X chromosome. A boy with one faulty copy is affected. A girl with one faulty copy is usually a carrier.

• Each son of a carrier mother has a 50 per cent chance of being affected
• Each daughter of a carrier mother has a 50 per cent chance of being a carrier
• An affected man passes the variant to all his daughters (who become carriers) and none of his sons
• And, critically, in the Australian cohort 39.6 per cent of cases arose from a new mutation — the mother was not a carrier. Which means roughly two in five families have no inherited risk behind the diagnosis

Also X-linked: one form of Emery-Dreifuss muscular dystrophy (emerin).

Autosomal dominant — myotonic dystrophy, FSHD, oculopharyngeal, the dominant limb-girdle subtypes (LGMD D), and the lamin A/C forms of Emery-Dreifuss.

• Each child of an affected person has a 50 per cent chance, regardless of sex
• The affected parent is frequently identifiable, but may appear unaffected in mild cases — particularly in myotonic dystrophy
• Myotonic dystrophy also shows anticipation: the repeat expands between generations, producing earlier and more severe disease. This is why a grandparent with cataracts, a parent with weakness and a grandchild with congenital myotonic dystrophy can be one family line. See myotonic dystrophy

Autosomal recessive — the recessive limb-girdle subtypes (LGMD R) and most congenital muscular dystrophies.

• Both parents are usually unaffected carriers
• Each sibling of an affected person has a 25 per cent chance of being affected and a 50 per cent chance of being a carrier
• Children of an affected person are usually carriers rather than affected, unless their other parent also carries a variant in the same gene
• There is frequently no family history at all, which is why recessive LGMD is so often a complete surprise

And new mutations occur in all patterns, which is why absence of family history never excludes a genetic muscle condition.

The practical instruction: get your inheritance pattern explained specifically, by a genetic counsellor, with your own family drawn out. Generic information gets applied wrongly more often than not — most commonly, families with a recessive LGMD worrying unnecessarily about their children, and families with a dominant condition not realising a 50 per cent risk exists at all.

What carrier status means, and the surveillance nobody gets

This is the most under-addressed issue in Australian muscular dystrophy care.

Women who carry a dystrophin variant are described as “carriers,” which implies they are unaffected. A proportion of them are not.

Cardiac involvement occurs in carrier women. The 2018 international care considerations are explicit about what should happen: a baseline ECG and imaging, preferably cardiac MRI, in early adulthood — and if negative, repeat assessment every three to five years.

Almost nobody in Australia is getting that. The usual experience is being tested for carrier status in the context of a brother’s or son’s diagnosis, told the result, handed information about reproductive risk, and discharged. No cardiac referral. No mention that one would ever be needed. No recall.

Some carrier women also have skeletal muscle symptoms — muscle pain, cramps, exercise intolerance, mild weakness, a raised creatine kinase — which get dismissed as unrelated, or as being unfit, or as fibromyalgia. A carrier woman reporting muscle symptoms deserves assessment rather than reassurance.

What to do if this is you:

Ask your GP for a referral for baseline cardiac assessment, and name the recommendation: baseline ECG and cardiac imaging, preferably cardiac MRI, in early adulthood, repeated every three to five years if normal.

If you have never been tested for carrier status and there is Duchenne or Becker in your maternal family, that is a separate conversation worth having through a state genetics service — free, in every state and territory — both for your own cardiac health and for reproductive planning.

And if you have muscle symptoms, say so, and ask for a creatine kinase test.

See the heart and muscular dystrophy.

Making sure the relatives actually get told

The 37 per cent figure is a systems failure, not a family one. Here is what closes the gap.

Ask the genetics service to draw the full family tree, including the extended maternal line in X-linked conditions and both sides in autosomal conditions. This is standard practice and it is the step that identifies who is at risk.

Ask for a family letter. Genetics services routinely produce a letter addressed to relatives, explaining the condition, the variant found, the inheritance pattern, and how to access testing in their own state. It is written to be handed on. Ask for copies, and ask for it to be written in plain language.

Then hand it on. Awkward, and better than the alternative. Most people would rather receive an awkward letter from a cousin than find out when their own child is diagnosed. The letter does the explaining, which makes the conversation much easier — you are passing on information rather than delivering news.

Prioritise by who needs it most urgently: women of reproductive age in X-linked families; anybody planning a pregnancy; and, in myotonic dystrophy and the lamin A/C conditions, anybody at all, because the cardiac surveillance is potentially life-saving regardless of reproductive plans.

Know that nobody can be compelled. Results are confidential and are not released without written consent except where a court requires it. Some relatives will not want to know, which is their right.

And in myotonic dystrophy, test upwards as well as downwards. The transmitting parent is frequently unaware they are affected. A fresh diagnosis means the older generation needs an ECG too, not only the younger one.

Reproductive options

All of these deserve a genetics appointment before a pregnancy rather than during one, and all are free to discuss through state genetic services.

Carrier or genetic testing first. Knowing your own status is what makes the other options available and meaningful.

Preimplantation genetic testing (PGT). Embryos are created through IVF, tested, and one without the variant is transferred. Available in Australia through fertility services, with cost a real factor though Medicare rebates apply to parts of IVF. Its chief advantage is that no decision has to be made about a pregnancy already underway.

Prenatal diagnosis. Chorionic villus sampling at around 11 to 12 weeks, or amniocentesis at around 15 to 19 weeks, each with a miscarriage risk under 1 per cent in experienced hands.

Non-invasive prenatal testing for fetal sex, which in an X-linked condition can determine whether invasive testing is needed at all — a female fetus in a Duchenne family will not be affected, though she may be a carrier.

Donor gametes.

Adoption.

Having children without testing, which many people choose.

And deciding not to have children, equally legitimate.

A specific note on pregnancy in myotonic dystrophy, because it carries risks beyond inheritance: polyhydramnios, preterm labour, and increased anaesthetic and cardiac risk for the mother. Pre-pregnancy counselling with an obstetric service that knows the condition is important rather than optional.

The family side

Beyond the genetics, there is the business of living with this, and it has features worth naming.

The length of it. A fifteen-to-thirty-year condition is not a crisis to be survived. It is a long stretch of a family’s life, through childhood, adolescence, adulthood and sometimes middle age, and arrangements built for a crisis do not survive it. Families who pace themselves do better than families who sprint.

The physical load, and the carer injury that ends arrangements. Get the hoist early. Get manual handling training, from a physiotherapist, for everybody who does transfers, repeated whenever equipment changes. Ask for it to be funded in the plan — it is a legitimate capacity-building item and it protects two people. Carer back injury is one of the commonest reasons a home arrangement stops.

The vigilance. Listening at night. Checking the ventilator. Noticing that the chest sounds different. This is what stops carers sleeping even when nothing is happening, and it is why respite that lets somebody sleep is worth more than respite that lets them go out.

The administration. NDIS applications and reassessments, equipment quotes, appointments across neurology, cardiology, respiratory, orthopaedics, physiotherapy, occupational therapy and dietetics, school, and the retelling of the whole history to every new clinician. Make one two-page summary and reuse it — diagnosis and variant, steroid history and adrenal suppression, cardiac medication and last imaging, respiratory function and ventilation settings, surgical history, current function, equipment, anaesthetic considerations, who to ring. It prevents more harm than anything else.

Siblings. Frequently the quietest people in the house, often doing more than anybody has acknowledged, and in recessive conditions carrying a 25 per cent risk of their own. They need their own information, their own counselling if they want it, and something in their life that has nothing to do with the condition.

And the guilt, which deserves naming directly. Parents who transmitted a gene they did not know they carried, and women who learn they are carriers after a son is diagnosed, frequently carry guilt that is enormous and entirely undeserved. Nobody chooses their genome, and in two of five Duchenne families the variant was new. This is worth hearing from a professional rather than only from relatives.

What to claim and who to call

Carer Gateway on 1800 422 737. Free, national, and most carers have never heard of it — counselling, coaching, peer support, respite, emergency respite, and in some cases financial help for practical support. Independent of the person’s own funding.

Centrelink. Carer Payment and Carer Allowance for the carer; Disability Support Pension for the person; Child Disability Assistance Payment where eligible. NDIS money is not income: it buys supports and contributes nothing towards living costs.

State genetic services, free, for the person and every relative.

Your state muscular dystrophy organisation. The national peak body is Muscular Dystrophy Foundation Australia, whose members are the state and territory organisations — several of which are registered NDIS providers and some of which run equipment programmes, camps, counselling, peer support and advocacy. This is consistently the least-used resource in the field.

JobAccess and the Employment Assistance Fund, for workplace modifications and assistive technology.

And superannuation and insurance. Total and permanent disablement cover and terminal illness provisions exist, are frequently held inside superannuation funds people have forgotten, and go unclaimed. Check every fund and request the wording before anybody resigns from a job, because many income protection policies require the claim to arise while employed.

Schools, and the conversations worth having early

For families with a child diagnosed young, school is where most of the practical work sits for a decade, and it goes well or badly depending almost entirely on how well the school understands what it is dealing with.

Tell them what it means functionally, not just the diagnosis. Progressive. Fatigue that is physiological rather than motivational. Fine motor decline that will affect handwriting. Help with the toilet and with personal care, increasing year on year. Falls risk, with fracture risk elevated by corticosteroids. And, in a subset of boys with Duchenne, genuine learning differences requiring assessment.

Ask for a formal individual education plan with funded adjustments, reviewed each term rather than annually, because the condition changes faster than an annual cycle.

Get the therapists into the school. An occupational therapist and physiotherapist who have seen the classroom, the corridor, the toilet and the playground will solve problems a clinic appointment cannot.

Anticipate the handwriting transition. Keyboard skills first and dictation after that, both learned while writing by hand still works. Exam provisions — extra time, a scribe, a computer, rest breaks — need to be in place and documented well before the exams that matter.

Protect physical education rather than exempting him from it. Modified participation keeps a child in the group; a blanket exemption removes him from it. The same applies to excursions and camps, which are worth fighting for with proper support rather than accepting as impossible.

Plan the toileting and personal care honestly, with a named person, a private space and a written plan. This is the issue children themselves worry about most and that adults discuss least.

Tell each new teacher each year, in a short written note. Institutional memory is worse than anybody expects.

And protect the social part above the academic part. A young person with a progressive condition whose friendships are maintained has a better life than one whose grades are. Everything that keeps him in the class, in the group and at the party is worth prioritising, and it is also what makes the transition after school survivable. See Duchenne into adulthood.