1/8/13

Why Does My Dog Have Seizures

A dog may seizure for any number of reasons. Just because a dog has a seizure does not mean that the dog has epilepsy. Just because I have a running nose does not mean that I have a cold. I could have a reaction to someone's perfume, I could have a sinus infection, I could have allergies, I could have ... . There are many tests to determine what exactly I have that is causing my running nose. However, there is no test in the medical industry for the existence of epilepsy (primary, inherited or idiopathic). To determine whether a dog has epilepsy or something else, a veterinarian or neurologist arrives at their diagnosis by a process of elimination. They determine what is not and then, hopefully, come to a logical conclusion as to what it is. The following is a list of conditions which can cause seizures in dogs. Each condition is discussed in the following sections: 

1. Brain tumor, Head injury 
2. Lyme Disease and Rocky Mountain Spotted Fever 
3. Distemper 
4. Environment - toxins 
5. Epilepsy 
6. hyper' and 'hypo' Conditions
  • Hyperglycemia
  • Hypoglycemia
  • Hypoxia or Hypoxemia
  • Hepatic Encephalopathy or Liver Disease
  • Renal (kidney) disease
  • Hyperkalemia
  • Hyperlipoproteinemia
  • "garbage" poisoning)
  • Tick Bites
  • Toxoplamosis (Toxo)
 7. Lissencephay 

The above list is not all-encompassing, but close, these items are the major causes for seizures in dogs.

1. Brain Tumor, Head Injury. 

A brain tumor is an abnormal growth in the brain. There are two types of tumors: primary and metastases. Primary tumors grow from tissues in the brain and their cause is unknown. Metastases are spread via the bloodstream from tumors in other places in the body. A tumor may be malignant. A tumor in the brain may also put pressure on the brain as it grows. Pressure on the brain tissue in the area of the tumor may cause: 
loss of vision 
motor coordination 
seizures Malcolm B. Willis and other noted authors state that a brain tumor is an "intracranial" cause of seizures. A tumor will probably occur in an older dog and "may leave the dog with a weak or paralyzed limb . . .". According to the Dog Owner's Home Veterinary Handbook, brain tumors occur in older dogs over 5 years of age. Outside of surgery, the MRI (magnetic resonance imaging) or CAT (computed axial topography) are the two most useful diagnostic tests to show brain tumors. Of all canine tumors reported, the brain tumor only accounts for 3.0% of these, a very small percentage. Over time, the tumor would grow and seizures would continue to occur and the anticonvulsant medications would not control the seizures caused by a tumor. An injury to the skull, possibly hard enough to crack the skull, would require a significant impact to cause an intra cranial disturbance. If such an event did occur, then, if seizures were to occur, they will not be observed immediately. The dog would not have seizures until weeks, or even months, after the event. If such an impact did occur, then the MRI would show an "abrasion" on the skull. The anticonvulsant drugs would not be effective against a skull injury. The anticonvulsant drugs are designed to stabilize the neurons within the brain cells. Phenobarbital and Primidone are designed to prevent the seizure from starting. Phenytoin is designed to stop the seizure from spreading. With a head injury, the neurons in the brain cells are already stable. The head injury itself is causing the seizure because of what Dr. deLahunta calls the "cerebral scar" which could be putting pressure on the brain and thus causing the seizures. If you are going to have an MRI preformed on your pet, also have a spinal tap - CSF analysis performed while the pet is under a general anesthetic. The results from the CSF should be normal. In the words of Dr. deLahunta "Cerebrospinal fluid (CSF) is a clear, colorless fluid that surrounds and permeates the entire central nervous system (CNS) and therefore protects, supports, and nourishes it." The CSF analysis is the best test to determine if any central nervous system inflammatory disease (i.e., distemper) is present. There is an accepted standard or count for the WBC and protein levels of the fluid. Any increase in the levels of these values is cause for concern. The presence of any inflammatory disease would be indicated by an increased protein level in the fluid. Similarly, the presence of any bacterial or fungal disease would be shown by an increased white blood count. The table below, derived from Dr. deLahunta's book Veterinary Neuroanatomy and Clinical Neurology shows the relationship between normal CSF readings and those associated with a disease. 



 Disease Process
 Pressure
 Red _BC_ (cmm)
 White_BC_(cmm) Protein_mg/dl

 Normal

<170

<5

 <5

 <25

 Canine Distemper Encephalitis

<120

23

 19

 49

 Toxoplasma Encephalitis

 256

 2

 17

 94

 Cuterebra Encephalitis

-

 10

 280

 98

 Canine Primary Reticulosis

-

 -

 58

 90

 Focal Myelomalacia (infract)

 -

 187

 4

 57

The text book Handbook of Veterinary Neurology, by Oliver and Lorenz, discusses the neurological exam. The first chapter is devoted to the discussion of the neurologic examination. In lay person's terms, the neurological exam evaluates how the nerves of the limbs are "talking" or communicating to the central nervous system and the brain and how the brain is responding. The examination is divided into 6 parts: 
  • observation 
  • palpitation 
  • postural reactions 
  • spinal reflexes 
  • cranial nerve 
  • sensation 
In the observation portion, the examiner notes the posture and movement of the dog. This can be done while the dog is allowed to roam and sniff around the doctor's office. In the palpitation portion, the examiner notes the muscle tone and size. They also check for any abnormalities in the skin and skeletal system. In the postural reaction portion, the examiner evaluates the responses that maintain the dog's posture. In the spinal reflex portion of the examination, the examiner evaluates the integrity of the sensory and motor components of the reflex arc. An example of the reflex arc in humans, is the reaction of tapping the tendon below the knee cap. The impact of the small mallet causes the lower leg to jerk. The reflex arc is the path that the nerve signal takes from impact at the knee to the brain, and then the brain sends the signal to the lower leg to somewhat kick. In the cranial nerve portion of the examination, the examiner notes the position of the head, notes the symmetry of the eyes and the pupils, notes the reactions of the nose when touched, evaluates the mucous membranes of the mouth and tonsils, the symmetry of the tongue, etc. Finally, in the sensation portion of the examination, the examiner evaluates the dog's response to pain based on the stimulus of the other tests.

2. Lyme Disease and Rocky Mountain Spotted Fever.


Both of these diseases are caused by a tick, a member of a super-family (Ixodoidea) of wingless bloodsucking arachnids, including many species that transmit diseases. The bite of the Ixodes genus tick causes Lyme Disease. This little critter is also knows as the deer tick, black-legged tick, or the seed tick. The tick attaches itself to the dog and begins to feed. The spirochetes (a spiral shaped bacteria that cause the disease) in the stomach of the tick move to the salivary glands of the tick and then into the host dog. If the tick is discovered within the first 24 hours after attachment, the chance of infection is very small. Appel and Jacobson, in their article CVT Update: Canine Lyme Disease, estimate that about 5% of the dogs in the geographical areas of the U.S. where Lyme Disease is endemic and are exposed to Lyme Disease, become affected, i.e., they develop the clinical signs of the disease. In other words, dogs have a small chance of acquiring Lyme Disease. A type of tetracycline antibiotic is used to kill the Lyme infection. "The proportion of dogs in endemic areas that develop clinical disease is relatively small." The canine citizenry responds fairly well to administered antibiotics.

Arthritis is the main sign of a dog affected with Lyme Disease. In humans the signs are chronic arthritis and "severe central nervous system involvement" according to Appel and Jacobson. The "Veterinary News" section of the April 1994 AKC Gazette, discuses the Western Blotting test for Lyme Disease. It is used to "conform or refute a positive (antibody) titer and it can also differentiate between a titer caused by a vaccine and a titer caused by natural exposure to the disease". In severe cases of Lyme Disease, seizures may be evident and they are much more likely to be evident in a human than a dog.

The July 28, 1997 issue of TIME Magazine, contains an informative article on Lyme's disease. It shows a map of the 48 states and indicates the number of reported cases of Lyme's disease in each state. A Center for Disease Control report in 1998 indicated that the upper midwest and east have the highest incidence of Lyme disease. The March 2000 issue of Your Dog (Vol VI, Number 3) published by the Tuffs University School of Veterinary Medicine has an excellent article on Lyme Disease.

3. Distemper. 

Canine distemper virus or CDV is one of many canine viral diseases. Distemper not only affects dogs and cats but also harbor seals, ferrets, the African lion and other mammals. Puppies lose their maternal antibodies by the time they are three months old. Therefore, CDV may be found in puppies 3 to 8 months old that have not been vaccinated, especially in kennel or shelter litters. Most canine veterinary manuals recommend that a brood bitch receive a booster vaccination before she is bred. The death rate for infected puppies can reach as high as 80 percent, according to a recent American Veterinary Medical Association study. CDV is usually transmitted through the air. However, it can be transmitted through physical contact with saliva, urine, feces, and probably human hands. The virus itself has a high mortality rate in the environment. This implies that for a dog to get the virus, it probably came in contact with an animal that is already infected or probably from a human hand that carried the virus. For example, a litter of puppies are always making contact with each other and being picked up by people. The means of transmittal in this instance is probably due to poor hygienic conditions in the whelping area or poor hygiene practices on the part of a breeder. The disease typically goes through two stages. By the 3rd day after exposure, a fever develops. There will be a watery discharge from the eyes and nose. The puppy may become lethargic and not eat. After a few days, the discharge turns to a thick yellow discharge (one article indicated a green discharge). Diarrhea is a problem at this point and can cause dehydration in a few days. The symptoms of the first stage of CDV may occur anywhere from 3 days to 2 weeks after the initial exposure. If the maternal antibodies are sufficiently strong, the puppy will recover sometime during this period. According to the UC Davis School of Veterinary Medicine Book of Dogs, the "most significant death loses in kennels
occur in pups 5 to 7 weeks of age". However, puppies that developed a fairly strong immune defense, may terminate the spread of the virus and expel it from their bodies. This usually occurs around 8 or 9 days after the initial exposure. These puppies will grow up to be very normal healthy dogs. In the second stage of CDV that begins at 2 to 3 weeks after the initial exposure, some dogs may develop signs of brain involvement. Depending on the level of the immune response of the puppy, the CDV may take one of 3 courses and will effect: 
  • lungs and upper respiratory tract 
  • intestines 
skin The respiratory signs (inflammation of the nasal passages and mucus membranes of the eyes) and the intestinal signs (diarrhea and dehydration) are followed by the neurological signs (circling, head tilt, rapid eye movements, partial paralysis, paralysis, convulsions, and insanity). Convulsions here mean seizures. According to the Dog Owner's Home Veterinary Handbook, "Dogs with brain involvement usually do not survive". Canine distemper may also affect the eyes by inflaming areas of the retina on the back of the eye. A dog that has been exposed to distemper and recovered would have evidence in its eyes, specifically on the retina. The areas of inflammation heal and leave scar tissue. The cornea may be affected by dry eye (keratoconjunctivitis sicca) as a secondary symptom to CDV. There is no cure for distemper. Antibiotics will not stop the spread of the distemper virus. They can only help to avoid the secondary complications, such as pneumonia, that may result. Fluids should be administered to counter act the effects of diarrhea. Only through the use of CDV vaccinations can the disease be prevented. Annual distemper booster vaccinations are recommended and most states require that distemper vaccinations be current in all dogs. Recommended periods for puppy vaccinations are at 6 to 8 weeks, 10 to 12 weeks, and 14 to 16 weeks and then on an annual basis. According to Oliver and Lorenz in their text Handbook of Veterinary Neurology, "Increased WBC and increased protein levels are expected with active inflammatory diseases. . . . Any disease that causes degeneration of nervous tissue without inflammation will cause an increase in CSF protein with little or no increase in cells". In the 40's and 50's John Paul Scott and John L. Fuller assembled a team of people to study the social behavior of dogs. Their research lasted nearly 13 years and involved the study of hundreds of dogs that were raised from birth to 1 year of age. Several factors such as feeding, sanitation, and disease control needed to be considered regarding the environment where the puppies were raised. All of their test puppies were given distemper vaccinations. The vaccinations were tested, unintentionally, when a dog with latent distemper was introduced into their test environment. All puppies that were not completely vaccinated acquired distemper. Their project was halted for 6 months to bring the distemper virus under control. As a result of the distemper epidemic, the vaccination schedule was changed to begin the vaccinations at 8 weeks of age, the time when puppies begin to lose their acquired immunity. 

4. Environment - Toxins.

The environment can be many things to a dog - the back yard, the kennel, the basement, etc. Wherever a dog can go, curiosity follows it landscapist is real close behind. In your back yard you may have Russian Olive trees, Codeless, pine trees, spreading junipers, apple trees and apples in the fall, plenty of grass, mushrooms when it is damp, many birds, garter snakes, etc.

In their Handbook of Veterinary Neurology on page 360, Table 16-21, Oliver and Lorenz have a list of toxins, their use around the house, the management of the toxin if ingested, and the prognosis for the affected dog. Of the 10 toxins that can cause seizures, the prognosis falls into 3 groups: 
good if treated early 
fair with treatment or treated early 
poor 

The table below shows a list of toxins that were compiled from data from Oliver and Lorenz, Handbook of Veterinary Neurology and Carlson and Giffin, Dog Owner's Home Veterinary Handbook


 Toxin

 Toxin Use

 Treatment

 Chance of Recovery

 Organochlorines

flea powders parasite control on dogs

sedation with barbiturates 

Poor

 Pyrethin

 external drug to control skin parasites

sedation
 good if treated early

 Bronethalin

 poisons

 activated charcoal

 fair

 Sodium flouroacetate

 rat poison

 sedation

 poor

Strychine

rat and or mouse poison

induce vomiting, sedation

good if treated early

 Thallium

 poisons
 Dithion early
poor

 Lead
 Insecticides and paintcalcium EDTA
 good with treatment

 Metaldehyde

rat poison, snail and or slug bait 

 sedation

 fair

 Methylxanthines (caffeine)

 chocolate and chocolate products

 sedation, fluids

 fair with treatment

 Zinc Phosphate

 rat poison

 oral and IV bicarbonates

poor


5. Epilepsy.

There are many things that can cause a seizure in a person or a dog. Epilepsy is a subset of one of the many things that cause seizures. Just because a dog has a seizure does not mean that the dog has epilepsy. Seizures come in two "flavors" or types, primary and secondary. Some external influence or some outside stimulus causes secondary seizures. With secondary seizures, the source is known. Primary epilepsy, also known by the names of idiopathic or genetic or inherited or true epilepsy, has no known source. A genetic factor may be highly suspected when seizures occur in dogs 1 to 3 years of age.

Before going into any detail about epilepsy, it is best to define the act of epilepsy itself, the seizure. By way of the thesaurus that comes with this word processor, the word "seizure" has the following synonyms: fit, convulsion, attack, epileptic fit, paroxysm, etc. A seizure begins unexpectedly and ends suddenly and does occur again. Epilepsy is referred to as being idiopathic when the seizures it causes have no known origin and the seizures do recur. Idiopathic, from the Greek language, is a combination of "idio" meaning "one's own or personal" and "pathy" meaning "disease". So idiopathic really means "one's own disease". One veterinarian that we talked to stated that idiopathic is really a fancy term for saying "we do not know".

As the uncontrolled discharge of neurons in the brain spreads, a partial seizure can become a generalized seizure. A generalized or grand mal is the most common form of a seizure. It is interesting to note that 'mal', meaning bad or wrong or ill, is generally used as a prefix, for example "maladroit" (bungling). The seizure itself is broken into 3 stages, the pre ictal, ictal and post ictal. Ictal is from the Latin 'ictus' meaning attack.

In a text book seizure, the dog will lose consciousness, will paddle or go through running movements, will chomp at the air and will salivate. In a seizure caused by strychnine poisoning for example, stiffening of the legs is observed but there is no leg movement or paddling.

In his exemplary text Veterinary Neuroanatomy and Clinical Neurology, Dr. Alexander de Lahunta of Cornell University, mentions that all dogs have a seizure threshold. A seizure occurs when this threshold is exceeded. Dogs with a low seizure threshold are divided into 2 groups - stimulus and non-stimulus. In the stimulus group, seizures may be caused by some external influence such as hormones, (e.g., estrogen which can lower the threshold to seizures in parts of the brain), fatigue or injury, and hyperventilation.

In the non-stimulus group, the seizures occur spontaneously, or as stated earlier, they have a sudden beginning. According to Dr. de Lahunta, the non-stimulus seizure is typical of many idiopathic epileptics.

The table below is similar to the one that appears on page 329 - Table 18-1 - in Dr. de Lahunta's text Veterinary Neuroanatomy and Clinical Neurology. The table lists the 3 categories that cause seizures and the agents under each category. Please note, that there are no agents listed under idiopathic epilepsy - they just happen.


 EXTRACANIAL

INTERCRANIAL 
IDIOPATHIC EPILEPSY

Hypoglycemia

 Degeneration's (poison)
 

 Hypocalcemia

 Inflammations (distemper, encephalitis)
 

 Hypoxia or Hyopoxemia

 Neoplasma (brain tumor)
 

 Hepatic Encephalopathy or Liver disease

 Injury
 

 Renal (kidney disease)
  

 Hyperkalemia
  
 Hyperlipoproteinemia  

 Gastrointestinal disease("garbage poisoning')
  

 Tick bites
  

 Toxoplasmoisi
  
   

Dr. de Lahunta also discusses the "interictal" period in his text. The interictal period is the time frame between seizures or clusters of seizures. The interictal symptoms are listed here: 
paresis - the diminished ability to move muscles or body parts voluntarily. 
infarct - localized tissue death. 
lesions - any disease induced abnormality of tissue or tissue function. A lesion could be an abscess, ulcer, or tumor. 
neoplasia - formation of a tumor or tumors. Assuming a brain tumor, the MRI showed none and any tumor growth would show
progressive deterioration of all activity. These symptoms are usually the result of one of the extracranial agents that are discussed in detail below. Dr. de Lahunta states in his text that "Dogs with idiopathic epilepsy do not have interictal signs." We will now briefly describe the agents mentioned in each category in the table above. 

6. 'hyper' and 'hypo' Conditions. 6.1 Hypoglycemia.

A dog with hypoglycemia (low blood sugar) usually has seizures prior to feeding when their blood sugar or glucose levels are at a low level. The signs of hypoglycemia depend on 1) level of the blood glucose and 2) the rate the glucose level drops. Some of the causes of hypoglycemia are: 
a pancreatic tumor that produces an insulin like substance 
liver disease 
cortisone deficiency 
diabetic dogs that obtain an insulin overdose Seizures are occasionally observed in hunting dogs during periods of excessive activity. 6.2 Hypocalcemia. 
This is an endocrine disorder (affects electrolyte, calcium, magnesium, and phosphorous) that is characterized by low levels of calcium. Typically the acceptable range of calcium levels from the blood serum chemistry is in the range of 8.5 to 11.0 (mg/dl). Loss of appetite in a dog will cause the calcium levels to decrease which in turn may cause seizures. Some dogs may develop muscle weakness early in the disease. Another symptom of hypocalcemia is cataracts. 6.3 Hypoxia or Hypoxemia. 
Hypoxia (Hypoxemia) is a condition of low blood oxygen levels that results in reduction in the capability of the red blood cells to carry oxygen. It may be the result of a disease of the lungs that prevents an adequate supply of oxygen getting to the brain thus causing seizures. 6.4 Hepatic Encephalopathy or Liver Disease.
Excess ammonia in the blood from liver disease may be a cause of seizures. Measurements of blood ammonia provides a truly reliable test to identify a dog with liver disease. According to the UC Davis School of Veterinary Medicine Book of Dogs, "It is the only test that can determine whether clinical signs of central nervous system dysfunction can be attributed to liver disease (hepatic encephalopathy)". Of all the signs of liver disease, anorexia (reduced food intake) is the first to appear and it too is a sign of hepatic encephalopathy. Portasystemic Shunts also known as Portacaval Shunt(s) fall into this category. This is the abnormal communication between the portal vein (coming from the gastrointestinal tract) and the vein which carries blood back to the heart (known as the posterior vena cava). During fetal life, the communication is normally there but shortly after birth it may close off. When the communications fail to close properly, the vessels serve as shunts so that portal blood flow does not pass through the liver for processing or detoxification before being delivered to the rest of the body. Small breeds such as Yorkshire Terriers, Maltese and Miniature Schnauzers are commonly affected by this. The signs will usually appear before 1 year of age. Some of the signs are: depression, seizures, ataxia (incoordination), vomiting, polydipsia (excessive thirst) and retarded growth. Blood chemistry panel results are usually normal. The best way to diagnose this is by performing an ammonia tolerance test. Diagnosis can be confirmed by an X-ray. The condition can be alleviated with dietary management or partial surgical closure of the shunt. (UC Davis School of
Veterinary Medicine Book of Dogs provided the information for the above descripition.) 6.5 Renal (kidney)disease. 
Kidney disease and kidney failure are two different conditions. The kidney fails when it is unable to perform its function of cleansing the blood of impurities. A kidney disease may hamper the kidneys from performing but it is still able to remove impurities from the blood. Uremia is a condition when there are high levels of urea nitrogen in the blood, other nitrogenous waste products in the blood, and the body pH falls below 7.0. The bodies buffering mechanisms that are under the control of the kidneys regulate the acidity in the blood and the body itself. High acidic levels of the body or acidosis may be the cause of seizures. The seizures are the result of the buildup of toxins (high nitrogen levels) in the blood. Uremia occurs at the terminal stages of kidney failure. It may also cause the body temperature to lower and may increase the respiratory rate. On page 270 of the UC Davis School of Veterinary Medicine Book of Dogs, the authors state "Failure to initiate therapy in a timely manner will result in irreversible damage to kidney tissue and ultimately death". Part of a complete blood work-up is the chemistry analysis. Included in that are the blood urea nitrogen (BUN) and creatinine, the two most common tests used to evaluate kidney performance. The normal BUN range for an adult dog is 10 to 25 (MG/DL) with the average being 17.5. The range for the creatinine is 1.0 to 2.2 (MG/DL) with the average being 1.6. 6.6 Hyperkalemia 
Hyperkalemia is the condition of a high concentration of potassium in the blood. Another term for this condition is Addison's disease. The heart rate of a dog suffering from hyperkalemia may be slower than normal. The condition may show itself as a generalized weakness in the dog and the condition becomes worse with exercise. 6.7 Hyperlipoproteinemia. 
Dr. de Lahunta's text Veterinary Neuroanatomy and Clinical Neurology has a small paragraph on this disorder but we were unable to find this disorder as it is spelled or described in any of the other veterinary texts we own. He states that "defective lipid metabolism" causes this disorder. Lipids are classified as simple and complex. Simple lipids do not contain fatty acids. Complex lipids are essentially fatty acids and include glycerides, glycolipids, phospholipids, and waxes (ear wax). Lipids can combine with proteins to form lipoproteins. Apparently this disorder does not properly break down the fatty acids in the blood and the affected dog may have seizures. Dr. de Lahunta states that the Miniature Schnauzer is the most commonly affected dog. A high concentration of lipids (triglycerides) in the blood is known as hyperlipemia. Other clinical signs of hyperlipemia include dullness, poor appetite, and rapid loss of body condition. 6.8 Gastrointestinal disease ("garbage" poisoning). 
Decaying and rotten garbage may be a breeding ground for staphylococcal and or botulism toxins. These may cause central nervous system stimulation, i.e., seizures. 6.9 Tick Bites. 
We have discussed tick bites and two of their diseases - Rocky Mountain Spotted Fever and Lyme Disease earlier. 6.10 Toxoplamosis (Toxo) 
The information that we obtained on Toxo comes by way of the internet. Toxo is a disease caused by a germ (protozan parasite - Toxoplasma gondii) and the most likely places of contact are cat feces, raw meet and uncooked vegetables. Approximately half of the people in the U.S. have the Toxo parasite, but the disease is dormant. This parasite is similar to giardia in that once a dog has giardia, it is dormant and may flare up at any time to affect the dog. Toxo has many symptoms and included in these are muscle spasms and seizures (neurologic difficulties). The symptoms worsen and the patient may go into a coma if the disease is not treated properly. The 2 most common drugs used in the treatment of Toxo are the combination of sulfadiazine and pyrimethamine. Depending on the dog's reaction to these drugs, other drugs may be substituted - clindamycin, dapsone, or doxycycline. In the winter of 1994 and 1995, Victoria B.C. experienced the world's largest outbreak of Toxo ever reported.

7. Lissencephaly. 

Dr. Cheryl L. Chrisman lists lissencephaly as a rare disease in dogs. This congenital condition (existing at birth) results in a smooth cerebralcortex. The cerebral convolutions are absent or unusuallly broad. In other words, it is a brain malformation and is manifested by a smooth brain.The symptoms of lissencephaly usually are evident within the first year of the dog's life. The dog may be difficult to house train, may be irritable,and display erratic behavior. According to Dr. Chrisman, "Generalized seizures are usually seen before 1 year of age". Anticonvulsant drugs maycontrol the seizures associated with this condition, but the other systoms mentioned are permanent. In a case study in the human population, 51 of 54 cases were female, leading reasearches to believe that the mode of inheritance is X-linked.