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Physiology/ Genetics, re. phenotype/ genotype

What is the phenotype/ genotype related to spinal cord injuries? Please cite refs websites and or journals

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Currently, in 70% of cases, HNPP has only one genotype or gene problem. This is the deletion of a segment of chromosome 17p11.2-12. This segment of the chromosome contains an important myelin gene, peripheral myelin protein-22 gene (PMP22). CMT1A, is genetically a mirror image, containing an extra copy of PMP22 at the same site that HNPP has a deletion. This one gene deletion, which causes HNPP, has different patterns of presentation.
Phenotype variability is basically a way of saying there are different ways that HNPP can look and act. These are the symptoms a doctor may see when a patient comes into the office. It is important for doctors to recognize the many different ways HNPP may manifest itself. Dr. Gareth Parry says, " We have tried to focus on the presenting feature of the disease. The rationale is that they need to be diagnosed correctly when they are first seen so we want people to recognize what the disease can look like when it first appears. Thus, the different phenotypes are those that are present at the time of the initial presentation." Dr Parry went on to explain that, over time, almost all patients go on to develop other features and they can change from one phenotype to another.
So, if phenotypes are a tool for the doctors, then why would we, as patients care about them? Actually for several reasons:
• Once they know that different phenotypes exist, people with HNPP are curious to know which type they are.
• Other family members may not have the same phenotype (which is one of the reasons this can be so hard to diagnose). Knowing the different phenotypes is a way to recognize the symptoms, so that those family members, who have not been diagnosed yet, can get diagnosed.
• Doctors are noting that people may switch from one of the five varieties or phenotypes to another. Tracking your own phenotype is a way to watch the progression of the disease. It should be noted, however, that some people don't switch and have the same phenotype for life.
• And finally, it is an alert to those diagnosed with CMT who may actually have HNPP instead.
NOTE! The Number of Phenotypes has changed. For the past several years, five phenotypes have been listed in the description of HNPP: Classic HNPP, Acute Arm Paralysis, Polyneuropathy resembling CMT(CMT), Confluent Mononeuropathy Multiplex (CMM) and, the Oligosymptomatic Phenotype. The Oligosymptomatic phenotype was, by far, the largest group and composed of those who had very few or very mild symptoms and who often have not sought medical help.
Some reviewers, of the medical literature, say, and with some justification, that a phenotype describes a clinical appearance and if the patients have no symptoms they don't have a clinical appearance. Thus the Oligiosymptomatic group cannot really be a phenotype. In keeping with the new thinking, the Oligiosymptomatic phenotype will be dropped. But a description of this largest group of HNPP carriers will be included after the four remaining phenotypes are discussed. 9/01
With the revised classifications there are currently four major phenotypes: Classic HNPP, Acute Arm Paralysis, Polyneuropathy resembling CMT (CMT) and Confluent Mononeuropathy Multiplex (CMM). In addition, many patients are asymptomatic or have so few symptoms that their disease is not recognized (previously the Oligiosymptomatic phenotype). The first two categories, Classic HNPP and Acute Arm Paralysis are characterized by episodic problems. Polyneuropathy resembling CMT (CMT) and Confluent Mononeuropathy Multiplex (CMM) Phenotypes are characterized by their more persistent and progressive symptoms that are moderate to severe. Both, CMT and CMM phenotypes can have numbness and weakness and other signs of a generalized neuropathy. A very simplified way to distinguish the latter two, is that in the CMT like phenotype symptoms are mostly symmetrical while in CMM they are not symmetrical. Each phenotype will be discussed in more detail below.
An Overview of Pressure Palsies
In order to understand the phenotypes of HNPP, one must first understand what is meant by the term "pressure palsy". When HNPP was first described by DeJong in 1949, it was called "bulb diggers disease". DeJong noted the periods of weakness and numbness (palsies), in bulb diggers, and thought they were caused by the kneeling position and pressure on the peroneal nerve. Thus the term pressure palsy. The spectrum of this disease, has evolved over the past 5 decades, but the concept of pressure palsies has remained. We do know that the pressure, which DeJong described, can and does cause the episodic numbness and weakness. But we also know that the nerves are in general very susceptible to injury and can also be injured by, external pressure, stretch, repetitive use and the build up of small injuries over time (cumulative effect). We also know that a progressive generalized neuropathy is an integral part of the disease, even in those patients who never recall having a pressure palsy episode (Parry).
Pressure palsies are typically described as transient (or intermittent or episodic), painless and often recurring symptoms of numbness (or tingling) and weakness. (Physicians will often use the term sensory and motor to describe the symptoms. Sensory means the sensations the patient feels, such as: tingling, numbness, or pain. And motor refers to strength or weakness). These episodes can be as brief as a few minutes, but can also last several days or even several months. Numbness may be as mild as the individual noticing that an area or limb does not have quite the same feeling as surrounding areas on the other side, or so severe as to feel like the area or limb has been shot full of Novocaine. Weakness also can vary between slight and barely there to so severe that the individual is unable to move a particular muscle group or the entire limb.
The most common problem sites are the wrists with carpal tunnel syndrome; the elbows with cubital tunnel syndrome; and the knees with peroneal nerve injuries. But any peripheral nerve - outside the brain and spinal cord- can be affected. It would be rare to see problems with nerves in the trunk, but fingers, elbows, scalp, shoulders, toes and feet are also frequent trouble spots.
Progression of HNPP
As mentioned above, over time, individuals can change for one phenotype to another. This typically involves changing from a milder or episodic form to a more permanent and generalized neuropathy phenotype, such as CMT or CMM. Although people who carry the HNPP gene deletion may have no symptoms initially, as time goes by, and as people are evaluated more carefully, it has become clear that mildly affected individuals often have symptoms attributed to other common disorders such as Carpal Tunnel Syndrome or lumbar disc disease. Some researchers believe that eventually (and this may take a lifetime), all individuals will show signs of a generalized neuropathy. Generalized neuropathy usually means more widespread symptoms of permanent numbness and weakness. The numbness is often a "stocking and glove" distribution and the weakness can cause foot drop and hand weakness. And it may not be until the general neuropathy has developed that the person first sees a physician.
For some the HNPP symptoms progress to a generalized neuropathy very slowly. For others the progression is quite rapid. Some are younger, others are older when this happens. Medical science does not yet understand why there is such a wide variance in symptoms, speed of development or age of onset.
There also appears to be a cumulative component to HNPP symptoms and activity. We tend to think of each nerve as one single nerve. In fact, there are many nerve fibers making up the one nerve. Some people report being able to do an activity one day without any problems. But have increasing symptoms if they continue to do the same activity many days in a row. When people experience increasing problem such as this, they are thought to be damaging more and more of the nerve fibers. Although nerve fibers are probably ...

Solution Summary

The phenotype/genotype related to spinal cord injuries are determined.