Annemieke wrote June 02, 2007 3:42 PM
A few years ago Jan Scholten had a Plumbum Phosphoricum videocase of a man with posttraumatic muscular dystrophy.
If I remember well he said that he had found that remedy specific for muscular dystrophy (ofcourse if it fits), but I don't know if the remedy had a proving.
--- In
minutus@yahoogroups.com , "Global Homeopath"
wrote:
Does anyone have experience in treating muscular dystrophy patient with homeopathic medicine? Kindly link cured cases if available on net.
Dear GH,
About an year ago this case:
“from "Dr. Deepak Sharma"
reply-to
minutus@yahoogroups.com
to
minutus@yahoogroups.com
date Jun 4, 2006 5:38 PM
subject [Minutus] A Case of Muscular Dystrophy”
Maybe the outcome of that case could help. For this you may like to contact him.
Also see extracts sent off list to Dr Deepak Sharma.
Regards.
Sarvadaman Oberoi
H 485 FF Ansals Palam Vihar
Gurgaon 122017 Haryana INDIA
Mobile: +919818768349 Tele: +911244076374
Website:
http://www.freewebs.com/homeopathy249/index.htm
email:
manioberoi@gmail.com
EXTRACTS
TF Allen
Encyclopedia of Pure Materia Medica
Plumbum Metallicim
- Glutei muscles and the large extensor on the front of the thigh were greatly wasted;while the biceps and flexors, from the trochanter of the ilium to the tibia, were unusually strong and active, indeed in a constant state of contraction, [a293].
TF Allen
A Primer of Materia Medica
Ammonium carb.
When the secondary effects of Ammonium carb. are studied it will be observed that there is a well-defined tendency to disorganization of the blood and numerous indications of defective nutrition, similar to scurvy, dark fluid haemorrhages, wasting of muscles, ulceration of the gums, looseness of the teeth and finally a low type of recurrent fever.
BLACKWOOD A. L., A Manual of Materia Medica Therapeutics and Pharmacology
Kalium hypophosphoricum
- This agent produces debility, attended with wasting of the muscular tissue.
CHOUDHURI N. M., A study on Materia Medica
Angustura vera
It is indicated when there are twitching or jerking of muscles, excitability to touch and noise, wasting of the soft parts and catalepsy. [Page 41. ]
CLARKE J. H., Dictionary of Practical Materia Medica
Iodium3x to 30C
- Given internally its power is much greater : the absorbents are stimulated to fresh activity; muscles, fat, tissues, and glands waste away, and general emaciation is the result.
GUPTA R. L., Directory of Diseases and Cures in Homoeopathy
Helonias
HELONIAS-Q, 3, 6, 2-3 drops dose in diabetes or albumin and amorphous phosphates in urine with emaciation, and wasting of muscles, great thirst, melancholia, restlessness, feeling of weakness, lameness in the back, numbness of feet, excessive urination, drowsiness and heaviness of head, better after little motion and when mind is engaged.
HALE E. M., Special Therapeutics of the new remedies
Podophyllum peltatum
According to Inman, all drastic purgatives may cause myalgia, and even cramps, and wasting of muscle.
Dr. coe, whose testimony is sometimes valuable, says: "Podophyllin is sometimes very tardy in its operation, not acting under eighteen or twenty hours, and frequently it will operate more freely during the second twenty-four hours than during the first. In cases of chronic disorders of the liver, at others in the spleen, and other viscera, considerable pain will frequently be experienced in the diseased organs during the operation of the medicine. Sometimes the pain will be in the liver, at others in the spleen, again in the kidneys(medicinal aggravation),also in the back of the neck and head, in the pleura, intercostal muscles, etc. (myalgia); but these symptoms will subside with the operation of the medicine." He thinks those are favorable indications, "showing that the remedy is at work arousing the dormant energies of the system. It is not necessary, however, to cause these pains.
HERING C., Guiding Symptoms of our Materia Medica
Calcarea carbonica
Muscular atrophy; muscles of back and limbs wasted.
VERMEULEN F., Concordant Materia Medica
Mang-act.
Mang. causes anaemia with destruction of the red corpuscles. Jaundice, nephritis with albuminuria. Fatty degeneration of liver. Paralysis agitans. Cellulitis, subacute stage, promotes suppuration and hastens regeneration. Symptoms of chronic poisoning, according to Professor von Jaksch, were involuntary laughter and involuntary weeping and walking backwards. Strongly exaggerated reflexes and physical disturbances, evidenced by men making fun of each other's gait. Paraplegia progressive; wasting, feeble and staggering gait. Wilson's disease. Paralysis agitans. Inflammation of bones or joints, & nightly digging pains. Asthmatic persons who can't lie on a feather pillow. Gout. Great accumulation of mucus. Growing pains and weak ankles. General soreness and aching; every part of body feels sore when touched; early tuberculosis. 2 Closely associated with iron. Special affinity for INNER EAR; larynx; trachea; periosteum of shinbone; joints; ankles and lower limbs. Bones are very sensitive. Pain extending to ear, from other parts. Everything affects ears. Diagonal pains. Yellow-green, lumpy or bloody discharges. Chronic arthritis, & infiltrated, glistening joints. Progressive muscular atrophy. Suppuration of skin around joints. Wants to lie down in bed, which amel. all the troubles. Typhoid fever; after; cases badly treated, with prolonged convalescence. Malignant ulcers & blue border, following slight injury. 5 Symptoms usually vary with the weather, always agg. at night. 11 All the senses less acute. Rheumatism & burning in small, red spots on chest, arms, hands and feet. Paralysis from decay of anterior portion of spinal cord. Chlorosis, if gastric symptoms and loss of appetite predominate.
IRWIN A., Seven Streams of Taosca Proving
Taosca aqua
Ireland:The Seven Streams of Taosca, Co. Clare
The cure there is for diabetes - muscular wasting,
Appearance bright with some solids in suspension.
Turbidity (N.T. U.) 0.32
Conductivity @ 25 oC (S/cm) 300
Ammoniacal Nitrogen (as NH4) (mg/l) {0.025
Nitrite Nitrogen (as NO2) (mg/l) {0.020
Nitrate Nitrogen (as NO3) (mg/l) 6.0
Total Hardness (as CaCO3) (mg/l) 140
Total Alkalinity (as CaCO3) (mg/l) 118
Colour(Pt/Co Scale) (Mg/l) 8.6
Odour .N.D.
PH 8.0
Total Iron (Fe) (mg/l) {50
Zinc (Zn)(mg/l) {20
Copper (Cu) (mg/l) {20
Lead (Pb) (mg/l) {5
Cadmium (mg/l) {1
Manganese (mg/l) {20
The chemical analysis denotes slightly hard water. The sample contained some vegetative and siliceous matter.
Taosca Aqua 3C - 200 available from
http://www.helios.co.uk/rx_list.html
Helios Homoeopathic Pharmacy 97 Camden Road, Tunbridge Wells, Kent TN1 2QR, UK. Telephone (01892) 536393 (24hr) / (01892) 537254 (9:45am-5:30pm) Fax (01892) 546850
Taosca Aqua Proving
Head
P7. My head aches as if two bolts were squeezing my temples and squeezing my head.
P7. A great deal of pressure on my temples and head area, tight as if my temples were being pushed together like the start of a migraine headache.
P6. Headache after eating chocolate.
P10. Right side of my head, eye and ear are very sensitive to touch.
P5. Flashes of light like rods, escaping from fixed focus when glancing down to left. I noticed when urinating. After visual symptoms sorrowful feeling moved up back of neck and head to frontal headache.
P10. (2nd day) Bad headache - so bad I woke at 4:00am - woken by headache and I've had it ever since. Feel horrible. It is a sinus kind of headache - flat behind my eyes - could feel my sinuses getting blocked yesterday after taking the remedy.
P10. Really terrible headache so bad that you feel nauseous, wondering about going to bathroom - might start throwing up or getting diarrhoea. Need to go right now, feeling too sick.
P10. Headache in the same spot, no movement. At back of nose, heavy.
P6. Slight headache, frontal, throbbing.
P9. Head pain left occiput pulsating, wavelike. Worse sudden movement.
P6. Tightness in head.
P5. Headache. Drinking wine with a headache last night.
P9. Headache started pounding pulsating from the movement from the anger I felt; lasted for 5-10 minutes. While I was angry my head pulsated all over especially in my eyes, pulsating throbbing pain. It went again when I calmed down.
Vertigo
P1. Vertigo evening.
P1. Feeling faint on turning; feel I could loose balance.
P1. Vertigo with slight shudder.
P1. Disorientation if I turn my eyeballs or on turning my head quickly like I’m going to feint. You’d need to hold onto something.
P2. Vertigo at the top of my head as if my brain turned suddenly. It lasted just a couple of seconds, but the feeling of disorientation lasted a little longer.
Eye
P10. Right side of my head, eye and ear are very sensitive to touch.
P9. Headache started pounding pulsating from the movement from the anger I felt; lasted for 5-10 minutes. While I was angry my head pulsated all over especially in my eyes, pulsating throbbing pain. It went again when I calmed down.
Vision
P5. Unusual visual symptoms
P5. Flashes of light like rods, escaping from fixed focus when glancing down to left. I noticed when urinating. After visual symptoms sorrowful feeling moved up back of neck and head to frontal headache.
Ear
P1. I put my hand on my ear. I felt a pain come out of my ears. I didn’t know what to do.
P1. Pain left ear in Eustachian tube.
P10. Right side of my head, eye and ear are very sensitive to touch
Nose
P6. Sinus. Post nasal drip.
Mouth
P10. My mouth is very dry and I am sleeping with my mouth open (unusual). Pretty severe pain.
P6. Metallic taste in mouth.
P5 Salivation, conscious of
Teeth
P11. All my teeth with cavities feel like there is pressure inside them. Concomitant with the teeth pain I am getting a pain like a sharp nerve pain in my left anterior deltoid.
P6. Front teeth sensitive.
P11. Pains in my teeth. Upper right side this afternoon.
Face
P5. Mouth ulcer beginning, lower lip, left.
P6. Tightness in jaw spreading to temples.
P6. Tightness in lower jaw muscle and chin.
P6. Tight feeling around lower jaw, left cheek, upper lip, behind nose. Pain in jaw muscles tightening.
P9. Could feel my sinuses getting blocked yesterday after taking the remedy.
Throat
P5. Itching in throat, compelled waking and rising at 6.45 am.
P1. I started to sing this morning, felt my voice really clear. I had a sore throat which got better from singing.
P2. Lump, plug sensation sadness, during
Stomach
P6. I seem to have become intolerant of chocolate. Headache after eating chocolate: taste in mouth slight nausea. Thirsty.
P6. Felt thirsty and had to go to the toilet to pee. Spirits felt slightly low.
P6. Woke up at 2 am from a dream. Still had the queasy feeling in my bowel and stomach.
P10. Appetite good now, ate like an elephant last nigh and today same - eating and eating
P6. Felt thirsty and had to go to the toilet to pee. Spirits felt slightly low.
P3. Stuffing my face with bad combinations of food, eating lots of sugary and stodgy things carbohydrates.
P2. Pain stomach after eating salad, relieved by eructations and flatus for a few hours.
P2. Repeating food.
P2. Nausea after eating fatty or fried foods or oily stuff such as smoked salmon and chicken.
P6. Thirst.
P6. Slight queasy feeling in stomach.
P5. Food temptations immediately to be satisfied. Butter, cheese, chocolate (though I knew better).
P1. Starving hunger, needing to eat.
P10. I have nothing to eat this morning. Just lying in bed since 4 am. Moving around - keeps changing
Abdomen
P2. Pain and flatulence after cabbage.
P2. Rumbling in abdomen.
P3. Flatulence copious and constant but especially in bed.
P3. Pains in abdomen, cramping. Stuffing my face with bad combinations of food, eating lots of sugary and stodgy things carbohydrates.
Rectum
P10. Energy ok but after a night of diarrhoea I wouldn't want to bounce around. I have eaten very little - like yesterday and then I got ravenous.
P6. Very loose bowel movements and frequent (6 a day, normally most would be 2 in one day).
P5. Anal sphincter swelling like a boil on the anal sphincter – caused immediate immense worry.
Felt something the size of a large pea, lasted for one day and vanished.
P2. Loose stool, copious, frequent (normal tendency towards constipation).
Sleep
P5. Slept very deeply since taking the remedy. Feel enthusiastic about the day to come even though frustrations are no less than usual maybe more so.
P10. I didn't sleep at all last night till 7am.
P10. Tossing and turning and couldn't get to sleep until 7. Didn't go to bed until between 12 and 1, just couldn’t sleep. Listening to radio, watching TV. Just haven't had a right sleep for several nights.
P6. Unremembered dreams. Sleep very soundly.
P6. Felt I had to get rid of excess energy so really worked hard in my Aikido class. The result is a black eye with a mistaken head butt. Despite the physical discomfort after training I slept surprisingly well. ‘Being’ rather than ‘doing’ seems attractive.
P6. Woke early thirsty.
P10. I didn't go to sleep until 4am. I was very awake and alive. Not so unusual but 4am is a bit late.
P6. Sleep deeply and late.
P5. Sleeping very soundly (usual sleep is light and frequently disturbed).
P8. Dreams normally vivid not vivid at all.
Bladder
P5. Awoke often for frequent urination (most unusual).
P4. Pain when urinating.
P3. Waking a lot at night to urinate (unusual).
Back
P3. Pain, dorsal area across my back in bed and shortly after getting up. It goes during the day.
P2. My neck went into spasm. The muscle on the right side became very tense and painful. Sharp pain. I couldn’t turn my neck – it was very painful from suppressed anger.
P2. Eruptions. Very itchy eruptions, pimples across my lower back, below the lumbar region.
P7. Pain in back muscles from mid way down on waking.
Extremities
P6. Strain in right arm from sports injury became worse.
P5. Numbness in right shoulder, muscle pain. Muscle to the left side of shoulder blade affecting the muscle that grips the pen when writing.
P2. Sharp pain in shoulder joint on waking. It goes as I walk about.
P3. Leg really aches deep in the back of my knee.
P3. Pain in groin after sitting all day.
P3. Pain deep in the middle of my heel.
P3. Pains back of knee and heel and armpits that extend down the bones. I’ve got a cold all week got it from exposure
P6. Right shoulder painful again – dragging pain down arm.
P5. Pain in shoulder and tingling in upper right arm which were worse when sitting down and looking upward.
P7. Tightness in foot like a cramp
P5. Burning pain like ember on my sock getting hotter to intense heat. Then it stops.
Female
P12. Vaginal discharge, much more excessive than the small amount that occurs regularly in the second week of menstrual cycle.
P10. I had a good sleep but woke up with a heavy period at 9 or 9:30am. It seemed to arrive very heavily (unusual) - I always get it in the morning. It didn’t continue like that, it came in a puff - no feeling and no problems. I used to have trouble - just ordinary - through the day. I wouldn't know and have to check every few hours.
Chest
P2. Pain across my chest and in my left arm.
P2. Tight pain like a band across my chest, heart region. Dull pain in left arm and then right arm.
Cough
P11. I have a cold. It seems to be worse in the evenings or it could be indoors in the warmth. It seems to be a long time coming maybe a week or so well certainly about 3 or 4 days.
P5. Irritating cough persists, evening after 8, lying on back, swallowing honey.
Expectoration
P2. Expectoration thick, glue like, yellow.
Generals
P2. Very tired.
P6. Difficult to get up I the morning.
P2Very deep prolonged exhaustion. I don’t feel as strong as I normally do.
P2 Exhaustion after least exertion and after eating
P1. Cold.
P1. Symptoms are left sided.
P6. Chocolate aggravates.
P10. Bought fruit - apples, bananas and oranges - only ate that. All I felt like eating.
P2. I’m very tired, worse for exerting myself. I don’t want to go outside and I have an aversion to exercise (usual but exaggerated).
P6. I seem to have become intolerant of chocolate. Headache after eating chocolate: taste in mouth slight nausea. Thirsty
P3. Stuffing my face with bad combinations of food, eating lots of sugary and stodgy things carbohydrates.
P1. I had a huge desire to eat bacon which I had not eaten ever before
Dreams
P5. No sense of anxiety in dreams (as is usual).
P2. Unremembered dreams.
Remark
Differential diagnosis: staphisagria, arg-nit., stramonium, anacardium, lac caninum, granite.
Symptoms Cured during proving by the remedy
Anger suppressed
Fastidiousness
Fears,
attacked
men
overpowering
to be seen
Lack of organization
Planning too much
Estranged from family
Delusions divided
Haughtiness
Mildness
Ulcers mouth, painful palate
ASSORTED ARTICLES – NOT HOMEOPATHIC
X-linked Disease Exceptions
http://www.ikm.jmu.edu/Buttsjl/ISAT493/ ... tions.html
The general rule of X-linked genetic diseases is that they are passed from mother to son, hence the reason they are "X-linked." Another general rule is that carriers are not affected by the disease because genes on their unaffected X chromosome compensate for the damaged genes on the affected X chromosome.
However, spontaneous mutations may cause X-linked genetic diseases to appear in family that has no history of them and no carriers. These spontaneous mutations can also cause females to be affected by the diseases. Since females have two copies of all genes on the X chromosomes, half of them are eventually inactivated. Generally, affected genes are inactivated and healthy ones prevail. If the healthy copy of a gene is inactivated , a female may be affected by an X-linked genetic disease.
And, finally, it is possible, but very rare for an individual to have the diseased, affected genotype and a completely normal phenotype . There is really no explanation for this, but it has been known to occur.
Definition:
http://www.biochem.northwestern.edu/hol ... sease.html
A genetic disease caused by a mutation on the X chromosome. In X-linked recessive conditions, a normal female "carrier" passes on the mutated X chromosome to an affected son
Alternative names
http://www.nlm.nih.gov/medlineplus/ency ... 002051.htm
Inheritance - sex-linked recessive; Genetics - sex-linked recessive; X-linked recessive
Definition
Sex-linked diseases are inherited through one of the "sex chromosomes" -- the X or Y chromosomes. Autosomally inherited diseases are inherited through the non-sex chromosomes (autosomes), pairs 1 through 22.
Dominant inheritance occurs when an abnormal gene from ONE parent is capable of causing disease even though the matching gene from the other parent is normal. The abnormal gene dominates the outcome of the gene pair.
Recessive inheritance occurs when BOTH matching genes must be abnormal to produce disease. If only one gene in the pair is abnormal, the disease is not manifest or is only mildly manifest. However, the genetic predisposition to disease can be passed on to the children.
In general, the term "sex-linked recessive" is usually referring to the more specific case of X-linked recessive.
Related terms and topics:
* Gene
* Chromosome
* Inheritance
* Heredity and disease
* Genetic counseling and prenatal diagnosis
* Sex-linked dominant
* Autosomal dominant
* Autosomal recessive
Information
X-linked diseases usually occur in males. Males have only one X chromosome, so a single recessive gene on that X chromosome will cause the disease. Although the Y chromosome is the other half of the XY gene pair in the male, the Y chromosome doesn't contain most of the genes of the X chromosome and therefore doesn't protect the male. This is seen in diseases such as hemophilia and Duchenne muscular dystrophy.
TYPICAL SCENARIOS
For a given birth, if the mother is a carrier (only one abnormal X) and the father is normal:
* 25% chance of a normal boy
* 25% chance of a boy with disease
* 25% chance of a normal girl
* 25% chance of a carrier girl without disease
If the father is has the disease and the mother is normal:
* 50% chance of a normal boy
* 50% chance of a carrier girl without disease
X-LINKED RECESSIVE DISORDERS IN FEMALES
Females can get an x-linked recessive disorder, although it would be very rare. An abnormal gene on the X chromosome from each parent would be required, since a female has 2 X chromosomes. This could occur in the two scenarios below.
For a given birth, if the mother is a carrier and the father has the disease:
* 25% chance of a healthy boy
* 25% chance of a boy with the disease
* 25% chance of a carrier female
* 25% chance of a girl with the disease
If the mother has the disease and the father has the disease:
* 100% chance of the child having the disease, whether boy or girl.
The odds of either of these two scenarios are so low that x-linked recessive diseases are sometimes referred to as “male only” diseases, although this is not technically correct.
Retinoschisis
http://www.blindness.org/visiondisorder ... sp?type=12
Juvenile Retinoschisis is an inherited disease diagnosed in childhood that causes progressive loss of central and peripheral (side) vision due to degeneration of the retina.
Clinical Description
Juvenile retinoschisis, also known as X-linked retinoschisis, occurs almost exclusively in males. Although the condition begins at birth, symptoms do not typically become apparent until after the age of 10. About half of all patients diagnosed with juvenile retinoschisis first notice a decline in vision. Other early symptoms of the disease include an inability of both eyes to focus on an object (strabismus) and roving, involuntary eye movements (nystagmus).
Vision loss associated with juvenile retinoschisis is caused by the splitting of the retina into two layers. This retinal splitting most notably affects the macula, the central portion of the retina responsible for fine visual detail and color perception. On examination, the fovea (the center of the macula) has spoke-like streaks. The spaces created by the separated layers are often filled with blisters and ruptured blood vessels that can leak blood into the vitreous body (the transparent, colorless mass of jelly-like material filling the center of the eye). The presence of blood in the vitreous body causes further visual impairment. The vitreous body degenerates and may eventually separate from the retina. The entire retina may also separate from underlying tissue layers causing retinal detachments. The extent and rate of vision loss vary greatly among patients with juvenile retinoschisis. Central vision is almost always affected. Peripheral (side) vision loss occurs in about half of all cases. Some patients retain useful vision well into adulthood, while others experience a rapid decline during childhood.
Inheritance
Juvenile retinoschisis is genetically passed through families by the X-linked pattern of inheritance. In this type of inheritance, the gene for the disease is located on the X chromosome. Females have two X chromosomes and can carry the disease gene on one of their X chromosomes. Because they have a healthy version of the gene on their other X chromosome, females typically are not affected by X-linked diseases such as juvenile retinoschisis. Sometimes, however, when carrier females are examined, the retina shows minor signs of the disease.
Males have only one X chromosome (paired with one Y chromosome) and are therefore genetically susceptible to X-linked diseases. Males cannot be carriers of X-linked diseases. Males affected with an X-linked disease always pass the gene on the X chromosome to their daughters, who then become carriers. Affected males never pass an X-linked disease gene to their sons because fathers pass the Y chromosome to their sons. Female carriers have a 50 percent chance (or 1 chance in 2) of passing the X-linked disease gene to their daughters, who become carriers, and a 50 percent chance of passing the gene to their sons, who are then affected by the disease.
Treatment
At this time, there is no treatment for juvenile retinoschisis. However, in some cases, surgery can repair retinal detachments. Ongoing scientific research is directed at identifying the gene that causes juvenile retinoschisis as the first step in developing means of prevention and treatment.
Individuals with juvenile retinoschisis may benefit from the use of low-vision aids, including electronic, computer-based and optical aids. Orientation and mobility training, adaptive training skills, job placement and income assistance are available through community resources.
Related Diseases
Juvenile retinoschisis can resemble other retinal degenerative diseases such as retinitis pigmentosa (RP), Goldman-Favre vitreoretinal dystrophy, Wagner's vitreoretinal dystrophy, and Sticklers syndrome. A thorough ophthalmologic examination, including diagnostic tests measuring retinal function and visual field, combined with an accurate documentation of family history, can distinguish between these diseases.
The Foundation Fighting Blindness is a research foundation dedicated to finding the causes, treatments and cures for retinitis pigmentosa (RP), Usher syndrome, macular degeneration and other rare retinal degenerative diseases such as juvenile retinoschisis.
Facts About Spinal Muscular Atrophy (SMA)
Muscular Dystrophy Association
http://www.mdausa.org/publications/fa-sma-family.html
DOES IT RUN IN THE FAMILY ?
When people learn that a family member has a genetic disorder, they often wonder how this could be the case if it doesn’t "run in the family."
The chromosome 5 type of SMA (the most common type) follows an inheritance pattern known as autosomal recessive, which often takes families by surprise. Diseases that are recessive require two gene flaws — usually one from each parent, but occasionally one from one parent and one that occurs as a fetus is being formed — before the disease shows itself. People who have only one gene flaw for a recessive disease are said to be carriers and usually show no symptoms. Often, a family has no idea that some members are carriers until a child is born with a recessive disorder.
The autosomes are the numbered chromosomes, that is, all the chromosomes except the X and the Y, which determine gender.
If both parents are carriers of SMN-related SMA, the risk of each pregnancy producing a child with the disease is 25 percent. This risk doesn’t change no matter how many children in the family have been affected previously. The "dice are rolled" with each new conception.
Genetic testing for chromosome 5 SMA is widely available for those suspected of having the disease, including unborn babies. However, as of 2003, carrier testing for SMA is more difficult and not widely available.
Genetic testing is expanding and changing rapidly, but its implications can be complex. It’s best to talk with a genetic counselor (you can obtain a referral through your MDA clinic) before embarking on testing.
In this family, two of the six children have SMA because they each inherited a flawed gene from each parent. The other children may be SMA carriers, able to pass a flawed gene to their children.SMA can occur even when there’s no family history
In contrast to chromosome 5 (SMN-related) SMA, the gene flaw causing most cases of spinal-bulbar muscular atrophy (SBMA) is on the X chromosome, leading to an X-linked inheritance pattern.
Females have two X chromosomes, and males have an X and a Y chromosome. Females who have a gene flaw on one X chromosome are usually considered carriers of an X-linked disease (although sometimes they can have a mild form of the disease). Males, in contrast, have no second X to protect them from the full effects of a gene flaw on the X chromosome and show the full effects of such a flaw.
Males who inherit an X-linked gene flaw generally have the disease. Each son of a woman who carries an X-linked disease has a 50 percent chance of inheriting the gene flaw and developing the disease. Each daughter has a 50 percent chance of inheriting the gene flaw and being a carrier herself.
Genetic testing via a blood test is available for SBMA.
For more on genetics and genetic testing, see the MDA publication "Genetics and Neuromuscular Diseases."
SUBJ (06/00): SEX-LINKED AND X-LINKED NEUROMUSCULAR DISEASES
http://www.mdausa.org/experts/question.cfm?id=311
When certain forms or types of neuromuscular diseases are called X-linked or sex-linked, what exactly does this mean?
REPLY from MDA: Ronald J. Schenkenberger, Director of Research and Patient Services Administration, MDA National Headquarters, Tucson, AZ
X-linked (sometimes referred to as sex-linked) means that a particular gene is located on the X-chromosome. The combination of X- and Y-chromosomes determines the sex of an individual. Men have one X-chromosome and one Y-chromosome. Women have two X-chromosomes. Since only one X-chromosome is necessary for a woman to function normally, one of the X-chromosomes in each female cell "turns off." In effect, the second X-chromosome is a "back-up" copy. The operative (functional) X-chromosome in each female cell is randomly determined and, thus, some cells function with one X-chromosome and some with the other.
Diseases are said to have an X-linked (or sex-linked) inheritance pattern if they result from a defective gene in the X-chromosome. Women who have a defective (X-chromosome) gene are called "carriers." X-linked diseases affect males almost exclusively. A son who inherits a defective (X-chromosome) gene from his mother will develop the disease because, as a male, he has only one X-chromosome. His Y-chromosome is received from his father. A daughter receiving a defective (X-chromosome) gene from one parent and a non-defective (X-chromosome) gene from another parent will be a carrier of the disease. Importantly, for each pregnancy, if the mother is a carrier, there is a 50 percent chance that each son will have the disease and a 50 percent chance that each daughter will be a carrier.
There is the special case of female carriers of X-linked diseases who experience some symptoms themselves. As noted above, the functional X-chromosome in any given cell in a woman is randomly determined. If one of the X-chromosomes has a defective gene, some cells will use the defective gene and some won't. It is the proportion of cells that use the X-chromosome with the defective gene that determines whether the woman will experience some symptoms of the disease. Most women will have no or very mild symptoms. However, there are rare cases where female carriers have such a preponderance of cells using the defective gene that they exhibit symptoms as severe as males. Females who have symptoms are called "manifesting carriers."
Examples of diseases that are X-linked include Duchenne (DMD), Becker (BMD) and Emery-Dreifuss (EDMD) muscular dystrophies and Spinal Bulbar muscular atrophy (SBMA). Charcot-Marie-Tooth disease (CMT) and Myotubular myopathy (MTM), among others, have at least one form known to be X-linked.
X-Linked Genetic Disease Prevention
http://www.microsort.net/Genetic.htm
The Genetics & IVF Institute is currently funding some of the costs associated with sperm separation for patients with a family history of an X-linked disorder. Please call 1-800-277-6607 for more information.
Most couples at risk for transmitting a X-linked condition are identified by either review of the family history or birth of an affected child. The ability to separate X- and Y-bearing sperm cells now provides new and previously unavailable opportunities for women who are carriers of X-linked disorders to have an unaffected child.
Over 500 X-linked diseases have been identified and occur in approximately 1 in 1000 live births. Many X-linked diseases are extremely debilitating or fatal including hemophilia (life threatening and debilitating spontaneous bleeding), Duchenne muscular dystrophy (the most common and severe form of the muscular dystrophies), Lesch-Nyhan syndrome (self-mutilation), and X-linked mental retardation (the most common cause of inherited mental retardation).
Couples at risk for transmitting a X-linked disorder can have an unaffected child by pre-selecting the sex of the child. In most cases, X-linked diseases are only expressed in the male offspring of carrier mothers. In these cases, girls born from couples at risk for transmitting an X-linked disorder are generally unaffected. The MicroSort technology significantly increases the chance of conceiving an unaffected child by sorting sperm for the correct (unaffected) sex, the X (female) chromosome-bearing sperm in most X-linked disorders. There are also some X-linked genetic disorders in which a couple could reduce the risk of passing on the disorder to their offspring by selecting Y (male) chromosome-bearing sperm.
Contact us at 1-800-277-6607, 703-876-3897, FAX: 703-995-4928, or email:
microsort@givf.com
X Inactivation in Females with X-Linked Dise ase
http://content.nejm.org/cgi/content/full/338/5/325
X-linked recessive disorders affect males, whereas female carriers are generally spared. This is due in part to the random inactivation in females of one of the two X chromosomes in all somatic cells. Normal females are thus a mosaic of two cell populations, each expressing the alleles from one X chromosome or the other. Thus, in female carriers of an X-linked mutation, approximately 50 percent of cells on average have the normal allele on the active X chromosome (with the mutant allele being on the inactive X chromosome), and these functionally normal cells are generally sufficient to spare females from the clinical effects of an X-linked disease.
Occasionally, however, females do have clinical manifestations of an X-linked disorder, such as the girl with the Wiskott–Aldrich syndrome described by Parolini et al. in this issue of the Journal.1 In some instances, this phenomenon is caused by mutations in autosomal genes (genocopies) that have the same clinical effect as a mutation in an X-chromosome gene in males. Others have cytogenetic abnormalities such as translocations involving the X chromosome. However, the patient described by Parolini et al., like a handful of previously described girls with Duchenne's muscular dystrophy, hemophilia B, and other X-linked diseases,2 ,3 is chromosomally normal and has a mutated copy of the Wiskott–Aldrich syndrome protein (WASP) gene on an X chromosome that is active in most of her cells.
Why doesn't her normal WASP allele compensate for the mutated one? We now recognize at least three mechanisms that can lead to such unbalanced, or "skewed," X inactivation.2 ,3 As proposed by Lyon,4 normal X inactivation (Figure 1A ) is a stochastic event in the early embryo. In each cell a choice is made independently, with an equal probability of the maternally or paternally derived X chromosome becoming the inactive X chromosome. The pattern of X inactivation in each embryonic cell is initiated from the X-inactivation center on the proximal long arm of the X chromosome by an unusual gene called XIST, for "X-inactivation–specific transcript."5 Unlike most genes, XIST does not encode a protein and, paradoxically, is expressed only from the inactive X chromosome, not from the active X chromosome, in somatic cells after X inactivation.
Figure 1. Three Mechanisms Leading to a Skewed Pattern of X-Chromosome Inactivation in Females.
Panel A shows the normal, random process of X inactivation. Maternally derived (blue) X chromosomes or paternally derived (purple) X chromosomes are inactivated at random independently in each cell early in embryogenesis. The inactivation of that X chromosome is maintained by methylation (m) of DNA cytosine residues. In mature tissue the resulting mosaicism reflects roughly equal proportions of maternally derived and paternally derived active X chromosomes, but in some cases the distributions are quite skewed (inset).
In Panel B, the embryonic X-inactivation process is the same as in Panel A, but one X chromosome bears a mutation (green dot) that hinders cell survival in a particular tissue. The resulting selective disadvantage leads to a skewed pattern of X inactivation in mature tissue. In Panel C, a mutation in the X-inactivation–specific transcript (XIST) gene results in the nonrandom selection of the X chromosome to be inactivated. The red arrows indicate the production of XIST RNA that spreads an inactivation signal up and down the X chromosome.
The XIST gene produces RNA that spreads an inactivation signal up and down the X chromosome on which it resides (Figure 1).6 X inactivation is subsequently maintained during cellular proliferation and differentiation by the continued expression of XIST and by methylation of DNA cytosine residues. Because the initiation of X inactivation is random, each tissue contains a mixture of cells that express maternally derived X-linked genes and cells that express paternally derived X-linked genes. Methylation-based assays of DNA from available tissues are commonly used to quantitate this mosaicism.1,7
The contribution of maternal or paternal active X chromosomes to the typical process of random X inactivation follows a bell-shaped distribution curve (Figure 1A). The tissues of normal women have on average 50 percent maternally derived and 50 percent paternally derived active X chromosomes, but in some women, especially certain female twins, this ratio is substantially different.2,3 At the extreme ends of the distribution curve are women whose X inactivation happens purely by chance to be so unbalanced that they can have clinical disease from a mutation on the X chromosome that is active in an overwhelming proportion of cells. This unfortunate pattern of inactivation could be the cause of the Wiskott–Aldrich syndrome phenotype in the girl described by Parolini et al.
In addition to the chance occurrence of unbalanced patterns of X inactivation, a second mechanism of skewed patterns of X inactivation involves a postinactivation growth disadvantage for cells with an active X chromosome that has a mutation that affects cell survival (Figure 1B). Female carriers of certain X-linked immunodeficiencies have such a selective disadvantage superimposed on the underlying pattern of inactivation in lineages affected by the genetic defect. If one of the X chromosomes has a mutation in a gene that normally enhances the proliferation, maturation, or life span of certain cells, then the cells of that lineage will have a nonrandom pattern of X inactivation that is weighted against the mutation-bearing X chromosome.
Examples of such cell lineages include the B cells of female carriers of X-linked agammaglobulinemia and the lymphocytes of female carriers of X-linked severe combined immunodeficiency.7,8 In fact, postinactivation selection against cells in all hematopoietic lineages with a mutation-bearing active X chromosome was first described in female carriers of the Wiskott–Aldrich syndrome.9 Therefore, it is particularly surprising that a girl who was heterozygous for a WASP mutation should be symptomatic. The X-inactivation pattern of blood cells in the girl described by Parolini et al. is the opposite of what would be expected as a result of the selective pressure present in carriers of the Wiskott–Aldrich syndrome. Moreover, the skewed pattern of X inactivation in the girl with the Wiskott–Aldrich syndrome was found in DNA from buccal mucosal cells as well as blood cells. This finding suggests that the effect is more general than that resulting from postinactivation cell selection, which is generally restricted to a single target tissue.
Perhaps the most likely mechanism of the Wiskott–Aldrich syndrome in this patient is a genetic defect in the X-inactivation process itself (Figure 1C). Kindreds have been identified in which several females have significantly unbalanced X-inactivation ratios, apparently inherited as an X-linked dominant trait from their mothers.2,3,10 Although the genetic basis for most such pedigrees is unknown, genes involved in the process of X inactivation are likely candidates. A mutation of the XIST gene has recently been shown to underlie a skewed pattern of X inactivation in multiple members of two unrelated families.11 Although the specific effects of the mutated allele are not known, it was found on X chromosomes that were preferentially inactive (Figure 1C). The mutation involved a single nucleotide in the promotor region of XIST, and a functional difference between the normal and mutant promotors was documented in vitro.11
With respect to the family described by Parolini et al., the fact that the patient's mother and maternal grandmother, as well as the patient herself, had a skewed pattern of X inactivation supports the hypothesis of a familial X-inactivation defect that led to the selective inactivation of the patient's maternally inherited X chromosome in all embryonic cells. Such a defect could be a mutation in XIST or in another, as yet unidentified locus involved in X inactivation. In either case, the patient's paternally inherited X chromosome, despite the occurrence of a new, deleterious mutation in WASP, would be the active X chromosome in all her cells, predisposing her to the same Wiskott–Aldrich syndrome phenotype as a male with a WASP mutation on his only X chromosome.
It has long been recognized that X inactivation has important consequences with respect to the clinical phenotype of female carriers of X-linked disease. With the documentation and study of families such as those described by Parolini et al.1 and others,10,11 it is becoming clear that unusual families with X-linked disease and familial patterns of skewed X inactivation also are important to an understanding of the process of X inactivation itself. Further studies of such kindreds will be needed to evaluate the relative frequency of each mechanism of unbalanced inactivation and should lead to an increased awareness of X inactivation and its clinical relevance.
Jennifer M. Puck, M.D.
National Institutes of Health
Bethesda, MD 20892-4442
Huntington F. Willard, Ph.D.
Case Western Reserve University School of Medicine
Cleveland, OH 44106
References
1. Parolini O, Ressmann G, Haas OA, et al. X-linked Wiskott-Aldrich syndrome in a girl. N Engl J Med 1998;338:291-295.[Full Text]
2. Willard HF. The sex chromosomes and X chromosome inactivation. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 7th ed. Vol. 1. New York: McGraw-Hill, 1995:719-37.
3. Belmont JW. Genetic control of X inactivation and processes leading to X-inactivation skewing. Am J Hum Genet 1996;59:1101-1108.
4. Lyon MF. Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 1961;190:372-373.
5. Brown CJ, Hendrich BD, Rupert JL, et al. The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell 1992;71:527-542.[Medline]
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7. Allen RC, Nachtman RG, Rosenblatt HM, Belmont JW. Application of carrier testing to genetic counseling for X-linked agammaglobulinemia. Am J Hum Genet 1994;54:25-35.[Medline]
8. Puck JM, Stewart CC, Nussbaum RL. Maximum-likelihood analysis of T-cell X chromosome inactivation patterns: normal women versus carriers of X-linked severe combined immunodeficiency. Am J Hum Genet 1992;50:742-748.[Medline]
9. Prchal JT, Carroll AJ, Prchal JF, et al. Wiskott-Aldrich syndrome: cellular impairments and their implication for carrier detection. Blood 1980;56:1048-1054.[Abstract]
10. Naumova AK, Plenge RM, Bird LM, et al. Heritability of X chromosome -- inactivation phenotype in a large family. Am J Hum Genet 1996;58:1111-1119.[Medline]
11. Plenge RM, Hendrich BD, Schwartz C, et al. A promoter mutation in the XIST gene in two unrelated families with skewed X-chromosome inactivation. Nat Genet 1997;17:353-356.[Medline]
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