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Hereditary Motor and
Sensory Neuropathy with Agenesis of the Corpus Callosum

This brochure on Hereditary Motor and Sensory Neuropathy with Agenesis of the
Corpus Callosum presents an overall description of the symptoms associated with
the disorder and of its effects on the people affected at different stages of
their lives. Should you have any questions after this reading, please contact
the resource services listed at the end of this document.

What is Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus
Callosum?

Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum
(HMSN/ACC) is a progressive hereditary neuromuscular disorder that mainly
affects people from the Saguenay-Lac-St-Jean (SLSJ) and Charlevoix regions of
Quebec, as well as people whose ancestors are native of these regions. Some
cases of HMSN/ACC have also been identified in others countries.

HMSN/ACC is responsible of the degeneration of the peripheral nerves involved in
both body movement and the perception of sensations. Irregularities are also
observed in the brain of the people living with the HMSN/ACC, predominantly in
the anatomical structure interconnecting the two cerebral hemispheres, known as
the corpus callosum. The corpus callosum is found to be totally absent in 57.8%
of patients, partially absent in 9.4% of them, and normally present in 32.8% of
people living with the disorder.

Men and women are equally affected. There are more than one hundred people
living with HMSN/ACC in Quebec, most of whom are localized in the SLSJ and
Charlevoix regions.

What are the symptoms of HMSN/ACC? How does the disease progress?

Symptoms appear shortly after birth or during the first year of life and are
characterized by a lack of muscular strength and a delay in the development of
psychomotor skills. HMSN/ACC is a slowly progressive disorder. It results in a
loss of mobility as well as backbone, hands and feet deformities. All people
with the condition show a light to moderate mental retardation. Presence or
absence of corpus callosum in the brain of people affected does not seem to
influence the severity or the nature of symptoms.

Infant children are less physically active than other children of their age
group. They have difficulties sitting and crawling. An intensive physiotherapy
and occupational therapy treatment will stimulate motor development. They
usually start walking around the age of two or three, with technical aids
support: lower limbs orthesis (feet and ankles), walkers, quadripods or support
canes. Whether using or not these aids, their gait will remain slow; they have a
poor balance and in most cases, tremors are observed on all parts of the body.
Once these children are too old to be carried in a stroller, a wheelchair will
be necessary.

Regarding the upper limbs, young children will be less prone to use their arms
and will often show hypersensitivity at the touch of objects. Fine motor skills
development is slowed. Arm motion and reaching for objects is slower. Handgrip
strength is weakened and keeping a grip on an object often requires extra
exertion. This weakness in the upper limbs sometimes causes muscle tremor under
strain.

Toilet training starts at a later stage and children are seldom ready to it
before age three. They will have a slower awareness to their environment.
Language development as well as learning capacity are also slower than normal.

Children will usually follow their kindergarten classes and their first year
elementary school in the regular system, with teaching aid support. By the
second or third year of elementary school, they will most likely be admitted in
a specialized class. Most children with HMSN/ACC will learn how to read, write
and count, but academics do not usually go beyond second grade.

Children will demonstrate social and moral judgment, will be able to conform to
the codes of conduct and to acquire a valuable general knowledge. They are
usually very sociable, hearty and affectionate, a cheerful child who likes group
activities and integrates well in the kindergarten environment or the school
activities.

In their teen-age years, most of the kids will be able to move around out of
home by themselves in a manual wheelchair. An electric scooter will give to
those capable of using it an opportunity to move on a longer distance. At home
or in class, a walker will help with ambulation, sometimes up to the age of
twenty or so. At that stage, the home environment must be adapted in order to
ease their mobility: outside wheelchair ramp, door access enlargement, adapted
tub or bath, etc. Different types of specialized technical aids are also used on
a regular basis: electrical bed, electric lifting device, etc. The car will also
need to be adapted to facilitate the transportation of the youth in the
wheelchair.

At twelve years of age or so, the child will undergo a surgical procedure aimed
at correcting the curvature or bending of the spine, or scoliosis. This surgery
will allow a better lung and other organs expansion, as well as a better body
alignment. Some youngsters wear a corset for a few years prior the surgical
straightening of the spine in order to postpone the moment when the surgical
process will be performed. However, the corset is not a substitute to the
surgery.

By the end of their teen-age years or at the beginning of adulthood, some
persons might suffer from psychiatric disorders ranging in severity. Anxiety and
agitation episodes, visual or auditory hallucinations and symptoms of depression
can occur, requiring a drug treatment. These problems are caused by dysfunctions
in the brain.

During adulthood, the person affected can move around using an electric
wheelchair but they will need assistance for all their personal needs. Weakness
in the respiratory muscles results in respiratory failure and a high risk of
bronchopneumonia that can sometimes lead to death. Life expectancy is shortened.
Average life span is 29 years, although many have lived up to their forties.

What causes HMSN/ACC?

HMSN/ACC is caused by a gene mutation localized in 1996 and identified in 2002
by scientists from Quebec. More than 99% of the persons affected show a common
single alteration or mutation in this gene; this mutation can be detected
through genetic analysis of a blood sample.

HMSN/ACC is caused by a gene mutation located on chromosome 15. This is an
autosomal recessive gene. The term autosomal means that this gene is located on
one of 22 pairs of chromosomes defining specific traits not related to sex
characteristics. The gene responsible for ARSACS is recessive: This means that
in order to have a child with the disorder, both parents must be carriers of the
gene; when the two (2) parents are carriers, they have 1 in 4 (25%) chances to
have child with HMSN/ACC with each pregnancy. (For a complete explanation of
autosomal recessive genetics, see the INFO sheet "Genetics: What is Autosomal
Recessive") Carriers of the HMSN/ACC gene show no symptoms of the disorder. Most
of these people do not know they are carriers.

How can I know whether I am a carrier of the HMSN/ACC gene?

Parents of a person affected with ARSACS are almost always carriers. The carrier
status of the ARSACS gene can be confirmed through genetic testing. This test is
available to members of families affected with the disorder and their close
relatives. This test may potentially be offered in communities where the risk of
being carrier of the ARSACS gene is high.

What are the risks of having an affected child?

When both parents are carriers of the HMSN/ACC gene, at each pregnancy:

There is a 1 in 4 (25%) chance that the child will have the disorder.

There is a 2 in 4 (50%) chance that the child will be a carrier of the gene.

There is a 1 in 4 (25%) chance that the child will neither have disorder, nor be
a carrier of the disorder gene.

If you have a family history of HMSN/ACC, you might wish to consult a geneticist
or a genetic counsellor. These health professionals will diagnose your chances
to have a child affected with HMSN/ACC, will suggest you to take a genetic test,
or discuss with you the family planning alternatives you may consider.

When a person is affected with HMSN/ACC:

To date, no person with this condition has been able to have children. This is
explained by the severity of symptoms. Whether the affected persons are normally
fecund is not known.

How is HMSN/ACC diagnosed?

The infant child is diagnosed following a clinical examination from the
paediatrician and the neurologist, as well as through the following medical
procedures:

Computed cerebral tomography: an exam of the brain performed with a highly
precise radiography technology.

Electromyogram (EMG): an analysis of the electrical activity in the arms and
legs muscles.

Genetic analysis.

What are the treatments for the disorder?

There are currently no treatments able to cure people with HMSN/ACC. However,
several health-care professionals acting as a team may help people living with
the disorder to maintain or improve their physical abilities and provide their
comfort. These professionals work mainly in the following medical fields:
occupational therapy, physical therapy, speech therapy, neurology, pneumology,
orthopaedics, nursing and genetic counselling.

The physical rehabilitation process throughout different stages of life:

Once the diagnosis is confirmed, the children will be assessed in physiotherapy.
The physiotherapist will assess motor development, joint mobility and technical
aids needs. A regular monitoring of these children during the preschool period
will be proposed in order to help develop motor skills (sit, crawl, stand up and
walk, with or without technical aids). The follow-up will also help maintain
correct posture maintenance, a good range of motion and good muscle strength.

During the schooling period, the children are monitored in physiotherapy, where
functional independence relating to transfer and ambulation processes, as well
as muscle strength will be assessed. The technical aids used by the children
will also be checked and adjusted if needed. In some cases, the children will
have to be followed-up again for a short period of time, especially after the
scoliosis surgery or during the phase when they start loosing functional
independence.

Once the diagnosis is confirmed, the children will be guided and monitored on a
regular basis in occupational therapy. This program will help foster motor
development, and maintain motor skills. Play and activities related to daily
living will be used to improve awareness of the surrounding environment and
enhance manual dexterity.

The occupational therapist will propose an early adaptive action at day care in
preparation for the social and school integration of these children, and may
also recommend a wide range of specialized equipment and changes to make to the
physical environment (in day care, at home and in school). Furthermore, the
occupational therapist will play an essential role during the school integration
and the whole schooling period.

The neurologist will ensure the life-long monitoring of the affected person, and
can answer questions from parents regarding the evolution of the disorder. A
neurologist can prescribe medications to treat problems that may arise during
the course of the disorder.

The pneumologist will assess the respiratory condition and prescribe appropriate
treatments: drugs, inhalation therapy, breathing exercises.

The orthopedic surgeon will assess and treat curvature of the spine (scoliosis)
and deformity of the limbs, and in some cases, may recommend wearing a corset
and orthesis, also suggesting the appropriate ways to ensure good posture when
in a wheelchair.

The nurse will provide all additional information about the disorder and
available services and resources. A nurse may offer support to help people with
the disorder and their family members cope with the disorder, provide guidance
with the administrative processes when required, and liaise with the various
health care professionals from the clinic and from other external services (CLSC
and others).

The genetic counsellor will provide information about the inheritance processes
involved in HMSN/ACC, the genetic testing available to the carriers of the
disorder's gene, and the family planning alternatives they may wish to consider.

What are the psychological effects of HMSN/ACC?

Learning that a child is diagnosed with HMSN/ACC is often an emotional shock for
the parents. Rehabilitation professionals will help them become familiar with
the exercises or play programs that will foster their child's development.
Parents' involvement is crucial in that rehabilitation process. A child with
HMSN/ACC needs more care and attention than an unaffected one; he will never be
as independent as the other kids. It is suggested that as soon as early
childhood, parents look for child care services, arrangements that will permit
them to have a break, or regular babysitting services. That will also help the
child develop his social skills and enhance his maturity. As parents often
experience tiredness and back pain, these arrangements will also prove to be
greatly beneficial to them.

A person living with HMSN/ACC goes through challenging phases that have major
impacts on their family: back surgery, foster care placement, etc. Each person
and each family will adapt differently to these steps that can be facilitated
through professional and community support.

Many of these people will live a happy life, surrounded with the love and
affectionate care of their family. Even though they are conscious of their
"handicap", they will seldom show signs of a great psychological distress
related to their condition. They know how to adequately express their needs and
feelings. The main social contacts aside from the family will be through school
or activities aimed at people with physical and/or mental disabilities. Some of
them will even experience love relationships.

Several adults live in foster care or institutional homes. This situation is
explained by the aging of the parents and the heavy care these patients need.

What about research on HMSN/ACC?

The gene responsible for the disease was discovered in 2002. Research is being
pursued in order to better understand the protein produced by this gene, and its
function. However, scientists have to get over several steps in order to find a
cure or a way to significantly reduce the symptoms associated with that disease.

What are the main resources available to people living with HMSN/ACC and their
families in the populations showing high incidence of the disease?

Clinique des maladies neuromusculaires du Saguenay-Lac St-Jean

(Saguenay-Lac-St-Jean Neuromuscular Disorders Clinic)

Carrefour de la Santé de Jonquière

2230 rue de l’Hôpital, C.P. 15

Jonquière, QC

G7X 7X2

(418) 695-7777



Clinique des maladies neuromusculaires de Charlevoix

(Charlevoix Neuromuscular Disorders Clinic)

Centre Hospitalier de Charlevoix

74, rue Ambroise-Fafard

Baie Saint-Paul, QC

G3Z 2J6

(418) 435-5150, ext. 2086 and 2087



Bureau régional de Dystrophie musculaire Canada (Muscular Dystrophy Canada [MDC]
Regional Office)

*Fonds ARSACS de l’ACDM

2230, rue de l’Hôpital, C.P. 15

Jonquière, QC

G7X 7X2

(418) 695-7760

*A MDC Funds mainly devoted to research on ARSACS.



Service de conseil génétique (Genetic Counselling Service) Complexe Hospitalier
de la Sagamie 305, St-Vallier C.P. 67 Chicoutimi, Qc G7H 5H6 (418) 541-1234,
ext. 2153 or 2081

Bureau provincial de l’ Association Canadienne de la Dystrophie Musculaire

(Muscular Dystrophy Association of Canada Provincial Office)

1425, boul. René-Lévesque Ouest, bureau 506

Montréal, QC

Acknowledgements

MDC wishes to thank Dr. Jean Mathieu, a neurologist and medical coordinator at
the Clinique des maladies neuromusculaires du Saguenay-Lac-Saint-Jean for
reviewing the document, as well as the various stakeholders of the clinic who
assisted with its conception. We also wish to address our thanks to Ms. Claude
Prévost, a genetic counsellor at the Complexe Hospitalier de la Sagamie, and
consultant at the Clinique des maladies neuromusculaires, for her precious input
in the brochure. The expertise of these professionals in the field of HMSN is
recognized everywhere in Quebec and around the world; MDC is happy to honour
them for their wonderful work with people affected and their families.


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