View source for Puzzle 2005 10 373 - Answer

{{NHJ|
|mainauthor= '''A.A.M. Wilde, Y.M. Pinto'''
|edition= 2005:10,373
}}
[[Image:Puzzle_2005_10_373_fig1.jpg|Figure 1|thumb]]

A 33-year-old lady visited the cardiologist because of
the sudden death of her brother at age 35. He
died while watching TV and had been without
symptoms as far as she was aware. Her father received
a pacemaker at the age of 48.
She had no complaints of dizziness, palpitations,
dyspnoea or chest pain. Her only complaint was some
weakness in her arms shortly after lifting them to get
something from above her head. Physiological examination
did not reveal any peculiarities. Her ECG is
shown in figure 1. Her echocardiogram is normal,
although cardiac dimensions were at the upper limit
of normal.

'''What is your diagnosis and what would your next step be?'''

==Answer==

The ECG shows sinus rhythm 60 beats/min. The QRS
width is normal (80 msec) and the QRS axis is almost
horizontal. Repolarisation is normal. The primary abnormality
is the prolonged PQ interval (≥300 msec).
In addition, the P wave has a very low amplitude (in
all leads).
The combination of prolonged PQ interval, lowvoltage
P waves and the patient’s history of muscle
weakness should raise the suspicion of a myopathy
associated with conduction disease. The family history
with one sudden death and a pacemaker in first-degree
relatives narrows this down even more to a ‘laminopathy’
i.e. a disease linked to mutations in the lamin
A/C gene. In that case referral to a recognised ‘muscle
neurologist’ is mandatory. In our patient the neurologist
found clear evidence of proximal myopathy. The
clinical diagnosis limb-girdle disease was made and
molecular diagnostic testing indeed revealed a
mutation in the lamin A/C gene.
The ECG findings are typical for Limb-Girdle disease
type 1b (the variant linked to lamin A/C mutations).
Conduction abnormalities almost always precede signs
of cardiomyopathy, which only progresses to overt dilated
cardiomyopathy in some cases. Particularly the conduction
system is sensitive to damage, most likely increased
fibrosis. In our patient the conduction system is
affected (long PQ interval and undoubtedly a prolonged
HV interval) and it is also likely that the atrial tissue is
abnormal as well (low-amplitude P waves). For a long time
pacemaker therapy was considered sufficient, but in recent
years it has become clear that affected individuals are at
risk for sudden death, even with a pacemaker.<cite>VanBerlo</cite> Prophylactic
ICD therapy at the time a pacemaker is implanted,
usually in the 3rd to 4th decade, is now advocated.

==References==
<biblio>
#VanBerlo pmid=15551023
</biblio>