38. Myotonic dystrophy.
|a.||is an autosomal recessive condition||False|
|b.||is beloved of examiners||True|
|c.||is due to a single gene defect on chromosome 19q||True|
|d.||is associated with severe mental retardation||False|
|e.||may cause reduced fetal movements||True|
|f.||may be associated with hydramnios||True|
|g.||the affected neonate may have breathing and feeding difficulties||True|
|h.||is associated with sub-fertility||True|
|i.||patients with the condition should be made known to the anaesthetist prior to having general anaesthesia||True|
|j.||the incidence is 1:5,000||True|
|k.||can be detected on chorionic villus biopsy or amniocentesis||True|
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.
~ 1 in 3 - 5,000.
Progressive condition, but rate of deterioration usually very slow.
Many affected individuals show no signs until middle-age.
commonest muscular dystrophy in pregnancy.
weakness and atrophy.
Particularly affects face and neck muscles.
Gives typical "haggard" appearance & ptosis.
and speech problems.
increased muscle tone, particularly affects the hands.
muscles are involved.
difficulty with walking, constipation etc.
muscle may be affected: labour problems and PPH.
if the baby is affected.
risk of miscarriage, premature labour and stillbirth.
risk of placenta previa.
heart conduction defects, testicular atrophy, frontal baldness and sub-fertility.
death occurs in 10% of more of those with conduction defects.
retardation in the congenital variety.
Fragile X, the genetics is based on repeats of a triplet of bases. (MCQ2,
severity increases with the numbers of repeats.
offspring of an affected mother can be more seriously affected.
is not likely in the offspring of an affected father.
problems with anaesthesia, muscle relaxants & opiates.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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,
hydramnios and reduced fetal movements if the baby is affected,
delay in labour,
Uterine muscle can be affected.
This can lead to slow progress in labour and PPH.
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).
antenatal referral should be made for specialist assessment.
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.
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.
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