38.     Myotonic dystrophy.

You need to know basic genetics:

    trisomy 13, 18 & 21, 45 XO, 47XXX, 47XXY, 47 XYY,

    Testicular Feminisation (Androgen Insensitivity Syndrome),

    BRCA1 & 2 etc. 

    and what the mechanics are of dominant, recessive and X-linked inheritance.

    What do you know of Fragile X?? (See MCQ2, question 40.)

We have an excellent young lecturer on the Course, but he can't cover everything in one hour.

I thought I would throw in myotonic dystrophy at this point to get you going!

Other topics will crop up in subsequent MCQs.  

Key facts for the DRCOG.

Autosomal dominant condition.

Incidence ~ 1 in 3 - 5,000.

Progressive condition, but rate of deterioration usually very slow.

Many affected individuals show no signs until middle-age.

The commonest muscular dystrophy in pregnancy.

Muscle weakness and atrophy.

Particularly affects face and neck muscles.

Gives typical "haggard" appearance & ptosis. 

Swallowing and speech problems.

Myotonia, increased muscle tone, particularly affects the hands.

Other muscles are involved.

Hence difficulty with walking, constipation etc.

Uterine muscle may be affected: labour problems and PPH.

Hydramnios if the baby is affected.

Increased risk of miscarriage, premature labour and stillbirth.

Increased risk of placenta previa.

Cataract, heart conduction defects, testicular atrophy, frontal baldness and sub-fertility.

Sudden death occurs in 10% of more of those with conduction defects.

Mental retardation in the congenital variety.

Like Fragile X, the genetics is based on repeats of a triplet of bases. (MCQ2, question 40.)

The severity increases with the numbers of repeats.

The offspring of an affected mother can be more seriously affected.

This is not likely in the offspring of an affected father.

Particular problems with anaesthesia, muscle relaxants & opiates.

Symptoms may worsen in pregnancy, but usually improve in the puerperium.

Affected individuals should wear a medical alert bracelet or carry a warning card.

Be careful with individuals with a +ve family history:

    they may be affected but not yet showing signs,

    and are still at risk from anaesthesia, opiates etc.

Expanded explanation.

There are 2 varieties of Myotonic dystrophy described, with the threat of more to come.

So we have MD types 1 and 2.

Type 2 is rare, so your answers will be based on type 1.

Unless you got an essay in the MRCOG, in which case you would demonstrate knowledge of the existence of type 2.

We will now restrict ourselves to type 1.

Also known as Steinert's disease.

His early patients illustrated many of the features of the disease.

It is an autosomal dominant condition and occurs in 1 person in 3-5,000.

It is progressive.

You could have the condition in a very mild form and not show symptoms until middle-age or later.

At the other extreme, there is a severe congenital form.

You will not be expected to know that it is on 19q (or that type 2 is on 3q).

I merely wished to show my erudition, though by the time the course comes round, I am sure that I will have forgotten!

It is associated with muscular weakness, sub-fertility and anaesthetic problems.

The affected mother may have an affected baby (50% risk) and associations are:

    hydramnios, probably related to reduced fetal swallowing & impaired bowel motility,

    reduced fetal movements,

    and, not surprisingly, breathing and feeding and swallowing difficulties in the neonate.

Myotonia means abnormal muscle tone.

There is slow relaxation of muscle after contraction.

This causes increased tone and stiffness.

Having difficulty releasing one’s grip, e.g. on a door handle, is described.

Like Fragile X, it is associated with triplet (CTG) expansions – see MCQ 2, question 40.

Basically, the relevant gene has the nucleotide triplet cytosine-thymine-guanine (CTG).

The triplet doesn’t occur in isolation, but in multiples or “repeats”, so you get CTG-CTG-CTG etc.

This is called the “expansion”.

Different books give different numbers for what is normal.

Luesley and Baker give the following:

    normal: 5- 35,

    pre-mutation: 36 - 40,

    full mutation: > 40.

Other sources put the full mutation at > 50, but I wouldn't get too hung up on the numbers.

The bigger the number of repeats above 40, the more severe the condition.

With small expansions, the disease might not show itself at a young age, if ever.

Normal people hand on their gene without increases in the number of expansions.

But those with the premutation or mutation are more likely to see an increase in the number of repeats in their offspring.

This particularly happens when the mother is handing on the abnormal gene.

It explains the phenomenon of “anticipation” in which the severity worsens from generation to generation.

This leads to the phenomenon of ever-earlier onset and increasing severity of symptoms.

So you could have a mother with little or no evidence of the disease.

Yet she produces an affected child.

If the mother has a child with congenital MD, there is a risk up to ~ 80% that any subsequent child will be severely affected too.

Congenital MD is severe and associated with huge expansions.

The affected first child is a measure of the instability of her expansion and the potential for further increases.

Chorionic villus biopsy can be used to assess the size of the fetal expansion and the degree to which the baby is likely to be affected.

DM affects multiple body systems, so produces a vast array of symptoms.

Weakness of facial and jaw muscles and associated facies and ptosis.

Facial expression suffers from the muscle weakness so the appearance lacks animation.

Distal limb weakness and myotonia can lead to problems with walking, climbing stairs and an increased risk of falls.

Stiffness is a common feature as are daytime fatigue and sleepiness (hypersomnia).

The alimentary tract can be affected with difficulty swallowing and constipation.

Cardiac conduction defects occur and an annual ECG is advised.

Sudden death from presumed ventricular arrhythmia occurs in 10-30%. 

Insulin resistance is reflected in an increased incidence of type 2 diabetes, hypercholesterolaemia, coronary disease and stroke.

Cararacts are more common.

Frontal baldness is described.

The condition may deteriorate in pregnancy or stay static.

The puerperium usually sees things return to how they were.

Pregnancy is complicated by:

    early and late miscarriage,

    premature labour,

    hydramnios and reduced fetal movements if the baby is affected,

    placenta previa,

    stillbirth,

    delay in labour,

    PPH,

    retained placenta.

Uterine muscle can be affected.

This can lead to slow progress in labour and PPH.

The uterus responds to syntocinon.

General anaesthesia poses particular problems particularly in the use of paralysing drugs and opiates.

They may severely suppress respiration and generate a need for prolonged ventilatory support.

Induction and inhalational agents can do the same.

It is imperative that the anaesthetic department knows of the woman with MD or suspected of having it (e.g. from the family history).

An antenatal referral should be made for specialist assessment.

Patients are encouraged to carry something to alert others to the condition, e.g. a medical alert bracelet.

The congenital variety comes with huge expansions, e.g. >2,000.

Significant mental retardation can be found with delay in speech, learning difficulties etc.

It is also associated with talipes.

There are lots of internet sites giving good data and with pictures of how it affects people.

You can get more information from the  Muscular Dystrophy Organisation. 

If you want to be super-expert, go to Wikipedia and OMIM.