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Limb Girdle Muscular Dystrophy
Fact Sheet # 13
Muscular Dystrophy Foundation (MDF) of South Africa
Mission statement:
The Muscular Dystrophy Foundation of South Africa is a non-profit organisation which supports
people affected by muscular dystrophy and neuromuscular disorders.
1.
Is Limb Girdle Muscular Dystrophy also known by other names?
No, this type of muscular dystrophy (MD) is only known by its original name, but its abbreviation
"LGMD" or "LGD" is often used.
2.
What is Limb Girdle Muscular Dystrophy?
The muscular dystrophies are inherited progressive disorders that cause breakdown of muscle
fibres. In the early days of muscular dystrophy research only four main types of muscular
dystrophy were known: Duchenne, Facioscapulohumeral, Myotonic and a final group which was
given the name of Limb Girdle Muscular Dystrophy (LGMD). It is now known that a number of
conditions with different causes and different genetic implications may present with symptoms
similar to LGMD. Therefore:
a. Some individuals earlier diagnosed as having LGMD did not have muscular dystrophy at all,
but one of several clinically similar disorders such as spinal muscular atrophy (an inherited
disorder of spinal nerve cells) or polymyositis (an inflammation of muscles which is not
inherited).
b. There are several types of muscular dystrophy that can have rather similar features, but
different inheritance patterns. Only a minority of people with muscular dystrophy that present
with weakness in the limb and girdle muscles actually have Limb Girdle muscular dystrophy.
It is therefore evident that the term Limb Girdle Muscular Dystrophy is still used to refer to many
disorders that may be quite different. This is important to note because these disorders differ in
their rate of progression, outcome and especially in their mode of inheritance - so that misleading
genetic advice may be given if a more precise diagnosis is not obtained. Some doctors now
consider that the name "Limb Girdle Muscular Dystrophy" should no longer be used at all. It is
advised that individuals who have been given this diagnosis should receive up to date advice
about the particular type of MD that is affecting them or members of their family. In paragraph 12
there is a list of disorders that may have been labelled as LGMD in the past.
3.
What causes Limb Girdle Muscular Dystrophy?
Many different types of LGMD have been identified, and have been associated with genes (or
regions) on the following chromosome (chr): Type 1A - chr 5q, type 1B - non-5q type, type 1C - chr
3p, type 2A - chr 15q, type 2B - chr 2p, type 2C - chr 13q, type 2D - chr 17q and type 2E - chr 4q.
Not all the genes or mutations (in these regions on the different chromosomes) have been
identified. However, the adhalin gene (chr 17q), the caveolin-3 gene (chr 3p), the calpain-3 gene
(chr 15q), gamma sarcoglycan gene (chr 13q) and the beta sarcoglycan gene (chr 4q) are some of
the genes that have been identified to date.
4.
What are the symptoms?
The LGMDs differ widely in clinical severity and age of onset. Muscle weakness and wasting of the
proximal and pelvic girdle muscles are the typical features of LGMD.
5.
Which muscles are affected?
The main features of the Limb Girdle type are that the muscles of the upper or "proximal", parts of
the limbs are mainly involved, the muscles of the face are spared and the symptoms of weakness
are usually first noted in late childhood, adolescence or adult life (thus differing from the Duchenne
type). Both males and females might be affected and their brothers or sisters are generally much
more often affected than their parents or children.
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6.
How is Limb Girdle Muscular Dystrophy inherited?
LGMD is inherited in an autosomal recessive or autosomal dominant pattern. Types 1A - 1C are all
inherited in an autosomal dominant manner. Here each child of an affected individual has a 50%
chance of inheriting the disorder. All the forms of Type 2 are inherited in an autosomal recessive
manner. Each child of a couple that are both carriers, has a 25% chance of being affected. As this
is a genetic condition, genetic counselling is strongly recommended. Genetic counselling provides
information on the inheritance pattern, risks to other family members, prognosis, psycho-social
support, as well as information about diagnostic testing, carrier testing, preclinical and prenatal
testing (where available).
7.
How is Limb Girdle Muscular Dystrophy diagnosed?
In the past the diagnosis of LGMD use to be made solely on a clinical evaluation. However, the
genes responsible for some forms of LGMD have recently been identified. There is therefore a
DNA test that can confirm the diagnosis of some of the forms of LGMD, particularly in individuals
who have a strong family history of LGMD. It is still important that the diagnosis of LGMD only be
made after all the alternatives have been considered and excluded by modern diagnostic
procedures.
8.
Is there a cure?
No, unfortunately there is no cure for this type of muscular dystrophy yet.
9.
Is there any treatment?
There is no specific treatment for LGMD.
10.
Is there a risk during anaesthesia?
It is always recommended that the presence of a muscular disorder be mentioned to your doctor.
11.
Has research been conducted on Limb Girdle MD in South Africa?
No research has been conducted on LGMD in South Africa, although a number of South African
patients and families have been included in overseas research efforts. There are multiple
international research efforts underway to unravel the causes of LGMD.
12.
Conditions that may have been labelled as LGMD in the past
Some of the conditions that may have been labelled as LGMD are listed below, together with an
indication of how they are inherited, or alternatively their non-genetic nature. Most of the nondystrophic disorders (that is conditions which are not strictly speaking muscular dystrophies at all),
which may be clinically similar to LGMD, are relatively easily distinguished from it and from each
other on muscle biopsy, though this may sometimes require specialised techniques - which are not
always available in South Africa. It can be more difficult to tell one sort of muscular dystrophy from
another on muscle biopsy alone. The following muscular dystrophies were most likely to have
been misdiagnosed as LGMD in the past:
(a)
Becker muscular dystrophy:
A milder variant of Duchenne MD; affects males; now identifiable by measurement of a protein
called dystrophin that is partially deficient in the muscle tissue in this disorder. In some cases it is
possible to make a diagnosis without muscle biopsy if a special blood test is able to detect that a
tiny part of the gene is missing (this is called a DNA deletion). Becker MD should be excluded in all
males who were thought to have LGMD. All the daughters of an affected male are carriers of the
gene and the boy’s mother, sisters and maternal aunts may be carriers. The sons of carriers each
have a 50% chance of being affected.
(b)
Manifesting female carriers of the gene for Duchenne Muscular Dystrophy:
Women who can transmit the gene for Duchenne or Becker muscular dystrophy are known as
carriers. Usually they have no muscle weakness, but occasionally they have a relatively mild form
of muscular dystrophy and are then known as manifesting carriers. If they have no near male
relative who is affected, the true nature of their weakness may be far from obvious and very
difficult to identify and they may have been diagnosed as having "Limb Girdle Muscular
Dystrophy". However for these women there is a 50% chance that each time they have a son he
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could have Duchenne or Becker MD, so the diagnosis is important. Women diagnosed as having
LGMD, especially if they have no family history of MD, should seek specialist advice about this
possibility. Research in molecular biology and on dystrophin in the next few years may help to
make diagnosis easier - at present it requires rather specialised and laborious laboratory
techniques. A very rare and special category of manifesting carriers has identifiable chromosome
anomalies (translocations) that are helpful in diagnosis.
(c)
Scapulohumeral muscular dystrophy:
An uncommon disorder characterised by predominant involvement of the shoulder muscles
beginning in adolescence or early adult life. The facial muscles are not affected.
(d)
Scapuloperoneal muscular dystrophy:
A group of disorders in which weakness of the muscles of the shoulders and below the knees is
characteristic. There are various modes of inheritance.
(e)
Emery-Dreifuss muscular dystrophy:
Muscle weakness, rather similar in distribution to the scapuloperoneal type, shortening of muscles
(giving contractures especially at the ankles, elbows and back of the neck) and cardiac conduction
problems are the main features of this X-linked disorder. It is not related to Duchenne or Becker
MD, although its pattern of inheritance is the same.
Once all of these other conditions have been excluded, a relatively small number of individuals
remain in whom the diagnosis of Limb Girdle muscular dystrophy is still appropriate.
Unfortunately, there are a number of different types of muscular dystrophy even within this group,
so that it is impossible to generalise about the likely clinical course for people with this diagnosis.
Progress is at last being made to sort out the basis of these conditions, which in the future should
lead to easier tests to distinguish them from one another.
(f)
Autosomal recessive muscular dystrophy of childhood:
This condition may be confused with Duchenne Muscular Dystrophy (DMD) in boys, and in girls
may be difficult to distinguish from the manifesting carrier state, though the mode of inheritance is
completely different. Either sex may be affected, and creatine kinase levels are very high. The
progression of the muscle weakness may be fast but is usually somewhat milder than DMD.
Muscle biopsy shows an active muscular dystrophy, but the protein dystrophin that is defective in
DMD is normal in the autosomal recessive form. This form of muscular dystrophy is common in
some North African areas, but relatively rare elsewhere. Research involving a group of families
from North Africa has localised the gene responsible for one form of muscular dystrophy to
chromosome 13. A protein associated with dystrophin has been shown to be abnormal in some of
the affected individuals. It is not known whether the form of autosomal recessive muscular
dystrophy of childhood seen elsewhere, is caused by the same genetic defect as the North African
form or not.
(g)
Autosomal recessive proximal muscular dystrophy of later onset:
This category is much rarer than originally thought, before techniques existed to distinguish LGMD
from the other conditions discussed earlier. There is variability again within this category, with
some individuals presenting in late childhood and others much later. The progression of the
disorder is also variable. A gene on chromosome 15 is responsible for some, but not all, cases of
this condition.
(h)
Autosomal dominant proximal muscular dystrophy:
This condition may be very difficult to distinguish clinically from the recessive form. It is rare, may
occur in either sex and may be transmitted from parent to child through several generations. It is
usually relatively mild. In theory, this disorder may be seen in isolated cases as the result of a
spontaneous "mutation" in the gene. In one large American family the gene for their condition has
been localised to chromosome 5, but it is not yet known whether the condition in other families is
caused by problems in the same gene or not. It is still important that the diagnosis of LGMD only
be made after all the alternatives have been considered and excluded by modern diagnostic
procedures. Non-dystrophic disorders, and muscular dystrophies, that may resemble LGMD are
listed below:
(i)
Non-dystrophic disorders which may resemble "Limb Girdle Dystrophies"
Spinal muscular atrophy (Kugelberg-Welander syndrome)
AR
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Glycogen storage myopathies
Lipid storage myopathies
Mitochondrial myopathies
Polymyositis
Hypothyroidism
Central core disease
Centronuclear myopathy
Multicore myopathy
Inclusion body myositis
(j)
AR
AR (Mit)
AR (Mit)
NG, Treatable
NG, Treatable
AD
AR
AR
NG
Muscular dystrophies which may be diagnosed as LGMD
Becker MD
XL
Facioscapulo humeral MD
AD
Manifesting Duchenne carriers
XL
Scapulohumeral MD
AR
Scapuloperoneal MD
AR or AD
Emery-Dreifuss MD
XL
(AR = autosomal recessive, AD = autosomal dominant, XL = X-linked, NG = not genetic, Mit =
mitochondrial)
13.
The role of the Muscular Dystrophy Foundation (MDF) in South Africa
The MDF supports individuals affected by muscular dystrophy and their families by offering emotional support,
information - including a series of fact sheets, referrals to genetic counselling and other clinics, formation of support
groups, assistance with special equipment, when possible, as well as financial support for research projects in
muscular dystrophy in South Africa. Creating public awareness for muscular dystrophy is also an important aspect of
our work, since the MDF relies solely on contributions from its members and other donors to provide an on-going
support service. Through our newsletter members are kept informed of all the activities and receive national and
international research updates. Please contact any office of the MDF if you require information about any of our
activities or programmes.
14.
Support group or contact person
Wanda Patten:
(021) 761-5238
Janeen Barber:
(014) 596-5549
Elizabeth Schoeman: (011) 660-3853
If you are unable to contact any of these individuals, please contact the MDF.
15.
Where can we find assistance?
Please contact your local MDF office for further information.
National Office
Cape Branch
P.O. Box 1535, Pinegowrie, 2123
P.O. Box 13449, Mowbray, 7705
Tel: (011) 789-7634, Fax: (011) 789-7634
Tel: (021) 448-8766, Fax: (021) 448-8766
email: [email protected]
email: [email protected]
Gauteng Branch
Kwazulu-Natal Branch
P.O. Box 1535, Pinegowrie, 2123
P.O. Box 290, New Germany, 3620
Tel: (011) 789-7635, Fax: (011) 781-3935
Tel: (031) 701-3801, Fax: (031) 701-3801
email: [email protected]
email: [email protected]
Local Clinics:
Please contact your local MDF branch for further information.
General Information:
Independent Living Centre (ILC): (011) 482-5476
Disability Info and Care (DIC): (011) 917-3284
Parking Concessions: Application to the Traffic Department of our your Local Authority.
Criteria: (a) if you need the extra width as provided by the special parking bays, or
(b) if you have a problem with walking long distances.
Special Equipment:
Phone either ILC or DIC for information on where to get special equipment.
MDF Website:
Please visit our MDF website (www.mdsa.org.za) for muscular dystrophy news updates.
16.
Please note
The treatments and drugs mentioned in this fact sheet are for information purposes ONLY. Please consult your
physician or other health care specialist for information regarding the use of any of the above. The MDF encourages
duplication of this fact sheet, under the following condition: that it is duplicated in its entirety - including the MDF logo
and full text. Only individuals authorised by the MDF may make changes to this fact sheet (the information "updated
by" and "last update" should be completed). Alterations to this fact sheet by any other party are strictly prohibited.____
This fact sheet was adapted from the following source(s): Fact sheet(s) of the Muscular Dystrophy Group of Great
Britain and Northern Ireland.
Compiled by: MDF-Gauteng Branch
Updated by: MDF-Gauteng Branch
Approved and Released by: National Office of the MDF
Last update: 30 May 2000
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