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| Journal of the New Zealand Medical Association,
08-September-2006, Vol 119 No 1241
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Myotonic dystrophy in Otago, New Zealand
Chris Ford, Alexa Kidd, Graeme Hammond-Tooke
Myotonic dystrophy (DM) is a dominantly inherited,
multisystem disorder, with at least two genetic variants—type 1, due to a
trinucleotide (CTG) repeat expansion on chromosome 19; and the rare type 2, due
to an expanded CCTG repeat on chromosome
3q.1 The clinical
features include weakness, myotonia, cataracts, cardiomyopathy, and gonadal
atrophy.
DM is the most common form of adult muscular dystrophy, and
the prevalence in the Western World has been reported to range from
2.2–5.5/100,000.2
Studies of DM in South Africa3,4 and
Canada5 have shown evidence for a founder
effect—where most individuals are descendants of a common ancestor. The
prevalence in New Zealand is not known, and there has been no report of a
founder effect.
There are also striking ethnic differences, DM being less
prevalent in South-East Asians and extremely rare in central and southern
Africans.6 There have been no reports of
the prevalence in different ethnic groups in New Zealand, but anecdotally, DM
seems to be rare in Polynesians.
Because DM is a multisystem disorder, patients require
management by multiple specialties, and it is important to ensure well-planned
and consistent care.7 It
is also likely to impact on quality of life, but there has been no study of
quality of life issues in a pure population of DM sufferers.
The aims of this study were therefore multiple. To
determine:
MethodsPatients with a clinical diagnosis of DM and resident
in Otago were identified through a search of computerised medical records in the
Neurology Department at Dunedin Hospital, and through a database of members of
the Muscular Dystrophy Association of New Zealand. Other involved family members
were identified through the index cases. Subjects were recruited via a letter
inviting them to take part in the study.
Patients were assessed at the hospital or in their
home. They were given a structured interview, a full neurologic examination, and
they also completed the SF-36 Health Survey.8 The investigators were not blinded
to the diagnosis, as the typical facial appearance usually made this
impossible.
For the quality of life survey, age and sex matched
control subjects with other neuromuscular diseases were identified from
Neurology Department records and recruited by letter. Results were also compared
with New Zealand norms.9
Student’s t-test was used to evaluate the results
of the SF-36 Health Survey, using the SPSS-PC software package (SPSS Inc,
Chicago, Illinois, USA).
The study was approved by the Otago Ethics Committee
and informed written consent was obtained from all participants.
ResultsPrevalence and demographics
of myotonic dystrophy in Otago—Twenty-one patients with a diagnosis
of DM were identified, of whom 18 agreed to participate. With a population base
of approximately 181,539 (New Zealand 2001 Census10) this represents a
prevalence of 11.6 per 100,000. Ten patients had DNA confirmation of the
diagnosis, including two that did not participate. For those patients without
DNA testing, diagnosis was based on clinical findings and electromyography. No
cases of type 2 DM were identified, either clinically or with molecular
genetics.The mean age of our patients was 45 years with a range of 16 to 74
years (Table 1); 61% were male and all were of European descent but born in New
Zealand, with no knowledge of
Māori ancestry.
Table 1. Demographic characteristics of myotonic
dystrophy (DM) patients and controls
Genetic
aspects—There were 12 families: 4 parent-child pairs, 2 sibling
pairs, and 6 patients with no other family members in Otago with DM. When the
pedigrees of the 12 families were investigated, one previously unknown link was
found between two of the families. In most families it was possible to trace
back the lineage only by two generations. But it was nevertheless clear that the
families were otherwise unrelated.
Clinical
features—Fourteen
patients were mildly affected by the disease. Their most prominent symptom was
muscle stiffness (myotonia), with mild weakness and minimal impact on gait and
walking. Three were moderately affected—patients found it difficult to
walk large distances, and had some dysphagia. One was severely affected, with
difficulties with walking and swallowing. All subjects were ambulant.
The most common initial symptom was myotonia, noted in 7
(38%). Fatigue was the most debilitating symptom according to 8 (44%) patients;
17 of the 18 patients reported significant myotonia, and 4 reported significant
muscle pain.
All had weakness of typical distribution and myotonia,
either clinically or electrophysiologically, leaving little doubt about the
diagnosis.
Several complications of the disease were present in the
patients, as shown in Table 2.
Table 2. Complications of myotonic dystrophy
AV=atrioventricular;
PEG=percutaneous endoscopic gastrostomy.
Management and access to
specialist services—Five patients lived in rural settings (more
than 1 hour from a major hospital), and 13 lived close to (or in) an urban
centre (less than 1 hour from a major hospital).
Six patients had been referred to a respiratory specialist
for sleep problems (4 from urban communities, and 2 from rural locations); 15
patients had seen a cardiologist (11 from urban communities, and 4 from rural
locations); 16 had had an ECG on record and 11 had had an echocardiogram; 5
patients had been referred to a speech language therapist (all from urban
communities); and 9 patients had been referred to an ophthalmologist (5 from
urban communities, and 4 from rural locations). Only four patients recalled
having been seen by genetic services. Seven were members of the Muscular Dystrophy Association of
New Zealand.
Quality of
life—18 out of 22 invited control subjects with neuromuscular
disorders agreed to participate. Their diagnoses were polymyositis (3 patients),
dermatomyositis (1), myasthenia gravis (4), Charcot-Marie-Tooth disease (5),
Becker muscular dystrophy (1), facioscapulohumeral muscular dystrophy (2),
myotonia congenita (1), and limb girdle muscular dystrophy (1). They were not
significantly different from the DM patients in age and sex ratio, and like the
DM patients they were all of European descent (Table 1).
There was no significant difference between the DM patients
and their matched controls in overall scores as measured by the SF-36 Health
Survey. However, the DM patients had significantly higher scores on the bodily
pain subscale than their paired controls (mean difference=20.22, t=2.692,
p=0.015), and the New Zealand norms (Table 3). Both the DM patients and the
controls differed significantly from the New Zealand norms on the subscales for
physical functioning, role physical, general health and vitality, but not for
social functioning, role emotional, and mental health (Table 3).
Table 3. Myotonic dystrophy (DM) patients and controls
compared to New Zealand (NZ) norms9.
DiscussionThis study shows that the Otago region has a prevalence of
DM that is more than double that reported in Western
Europe.1 The population base was derived
from the 2001 census10, and the Otago
population may have increased slightly, but this is unlikely to affect the
result by more than 2%, which was the growth of the Otago population between
1996 and 2001. The reason for the high prevalence is unclear, and it may just be
chance that produced this result, as the population studied was quite small.
As the neurology service for the region is concentrated in
our hospital, with limited private practice, case ascertainment may have been
better than previous studies. Our department’s subspecialty interest in
neuromuscular diseases was not a factor, because we excluded patients not
domiciled in Otago. There was no evidence for a founder effect. As we may have
missed patients who had not been diagnosed or had not been referred and were not
members of the Muscular Dystrophy Association of New Zealand, the true
prevalence of DM may be even higher.
All
patients indicated that they were of purely European descent and none were
Māori. This may reflect the high proportion of Europeans (93.7%) and low
proportion of Māori (6%) in the Otago
population,10
or indicate that Māori are less likely to seek medical care. However, an
informal (unpublished) survey of all neurologists in New Zealand found no DM
patients of Māori or Pacific Island ancestry.
DM is rare in sub-Saharan Africans, and this is reflected in
a lower frequency of large-sized normal alleles (CTG repeats) in this part of
Africa.6,11 Outside of Africa, the
frequencies of large-sized normal alleles and the prevalence of DM are highest
in West Europeans and Japanese and lowest in South-East
Asians6. As larger alleles are more
unstable, it is postulated that people with large-sized normal alleles provide a
pool of individuals, who may have descendants with DM.
The original expansion of CTG repeats into the large-sized
normal range may have occurred in a north-eastern African population prior to
the migration of the ancestors of the European and Asian population out of
Africa, and most cases of DM may be descendants of these
individuals.6
The prevalence of DM in Polynesian populations is unknown,
but our inability to identify any cases in the
Māori or Pacific
Islander populations suggests that it is low. If so, the prediction would be
that Polynesians have a low frequency of large-sized triplet repeats, perhaps
reflecting their origins in South-East Asia. However, the frequency of large
sized alleles is high in Micronesian and Australo-Melanesian populations
(also thought to originate from South-East Asia), while the prevalence of DM is
unknown.6 In Polynesians, neither the
prevalence of DM or the frequency of large alleles is known, and more research
is clearly needed.
We attempted to assess the standard of care of patients with
DM. As this is a multisystem disorder, management can be complex and requires
input from several specialties. It is not clear from our data whether patients
received adequate input from other specialties. However, it is concerning that
not all patients had a recent electrocardiogram, and there was one patient with
visual symptoms who had not yet been referred for ophthalmological evaluation.
The low rate of referral to genetic services probably
reflects the lack of a genetic service in this region at one time, but does
suggest a degree of inertia in referring patients already known to our service.
Review of the notes suggested that care was haphazard and non-systematic. It has
been recognised that clinical guidelines and integrated clinical care pathways
are important in the management of complex genetic
disorders.7 Our findings emphasise the
need to make use of such protocols in myotonic dystrophy, and we plan to
introduce a clinical care pathway into our clinical practice.
Although overall quality of life, as measured by the SF-36,
was no different to patients with other neuromuscular conditions, DM patients
had significantly higher scores on the bodily pain subscale than paired controls
and New Zealand norms. Surprisingly, only four DM patients reported significant
muscle pain during the interview, so it was not clear why they scored so high on
this subscale. Muscle pain has been commonly reported in other studies
however.1
Both the DM patients and the controls had worse scores for
physical functioning, role physical, general health, and vitality, when compared
with New Zealand norms. DM patients and neuromuscular controls were not
significantly different to the general population for social functioning, role
emotional, and mental health, which is surprising for a disabling group of
diseases.
No previous studies of muscular dystrophy have utilised the
SF 36 Health Survey. However, several Swedish studies have examined quality of
life in muscular dystrophies, including myotonic dystrophy, using the Sickness
Impact Profile and the Kaasa
test.12–15 In these studies, no
significant differences were found between types of muscular dystrophy, and
increasing disability over 5 years was correlated with decreased coping and
quality of life. Quality of life was significantly related to forced vital
capacity and fatigue, but less so to other respiratory and cardiac parameters
and performance of activities of daily living.
Myotonic dystrophy is an important neuromuscular disease in
Otago, affecting quality of life and requiring significant health resources.
Management of these patients could be improved with the use of an appropriate
clinical care pathway.
The apparent low prevalence of
myotonic dystrophy in
Māori and other Polynesians is intriguing and, if confirmed, may help
inform theories of the genetic origins of these populations.
Author information:
Chris Ford, 5th-year Medical Student, University of Otago Medical School,
Dunedin; Alexa Kidd, Clinical Geneticist, Central Regional Genetic Services,
Capital Coast Health, Wellington; Graeme Hammond-Tooke, Senior Lecturer in
Medicine, Department of Medical and Surgical Sciences, University of Otago
Medical School, Dunedin
Acknowledgements:
Chris Ford was supported by a summer studentship from the Dunedin School of
Medicine, University of Otago, Dunedin. We thank Associate Professor Peter
Herbison for statistical assistance and the Muscular Dystrophy Association of
New Zealand for their help.
Correspondence: Dr
Graeme Hammond-Tooke, Department of
Medical and Surgical Sciences, University of Otago Medical School, PO Box 913,
Dunedin. Fax (03) 474 7625; email GraemeH@healthotago.co.nz
References:
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