Central Nuclear Myopathy essay

Central Nuclear Myopathy
By Jon Cline

Although patients with the extremely rare and sometimes life-threatening disease, central nuclear myopathy, will never be able to walk, or do some of the more athletic things people who do not have it do, they are still capable of leading normal lives. Most patients capable of communicating through computers or by sign language. This enables them to work; hence lead their own lives, with simply the assistance of others. If one was to look at a child just born with central nuclear myopathy, one would see a baby not even able to blink its own eyes, yet through modern technology and research conducted at some of the most prestigious laboratories and schools, scientists have been able to develop medications which help these helpless babies build muscle mass. While affecting the patient by destroying potential muscle mass, central nuclear myopathy also affects each patient’s life in different ways.

One might wonder what central nuclear myopathy (CNM) even is. It is an extremely rare, slowly progressive, muscle disease, somewhat similar to atrophy. Michelle Hemsworth, Pediatric RN, stating “there are 25 reported cases of CNM in the U.S., and fewer than 1,000 in the world,” could validate the rareness of this disease. According to www.census.gov, for every baby born with CNM, 6,366,904 are born without it. Although not much is yet known about CNM, scientists have been able to conduct experiments with certain medications (such as 3, 4 DAP), to great effect. Through much study, scientists were recently able to learn what causes CNM: during child development, certain “defective genes” create problems inside developing muscles.

Some of the effects of central nuclear myopathy are obvious, while others can take some time to notice. One of the most noticeable features of CNM are the prominent features each patient has. Prominent features include a long face, a wide forehead, large eyes, and long fingers. Another of the biggest and most noticeable effects of CNM is having very little, if any at all muscle in the entire body. This causes the following problems: Compromised Respiratory Status, scoliosis (a disorder in which the spinal cord is intensely convex), inability to cough one’s clear throat; pneumonia, inability to talk, possibility to make some noises and whisper, kyphosis (a disorder in which the chest appears to be “caved in”), and unable to eat for calories. Because the patient cannot eat, they will normally receive nutrients through a gastrostomy tube (commonly known as a ‘G-tube‘), which is a tube leading from the inside of the stomach to a bag filled with nutrients. Although the patients cannot eat for calories, they can occasionally eat for fun. Another of the biggest problems with having no muscle is that they cannot choke to clear their throats. They will either receive the Heimlich maneuver, or suffocate.

Although there are still many mysteries surrounding how central nuclear myopathy is formed, and many certain questions about it, scientists have been researching very hard for a few years, and now believe they have an idea of how it is formed. One-thing scientists know is that according to the Harvard Neuromuscular Disease Project, CNM is clearly X-linked. This means that one can only find CNM in an X-chromosome. If a female has one X-chromosome not containing the mutation for CNM, and one other X-chromosome containing the mutation for CNM mates with a male who has one non-CNM X-chromosome and one Y-chromosome (obviously not containing CNM since CNM is x-linked), the only possible way to have a baby born with CNM would be for the mother’s X-chromosome containing CNM to be the dominating chromosome and for a male to be born. If the parents had a daughter instead of a son, the daughter could only be a CNM-gene carrier, and not be affected because she has two X-chromosomes, so neither would be recessive or dominant. Overall, when one of the parents (usually the mother) is a carrier, there is only a 25% chance of having a baby born with CNM. For these reasons, only males can have CNM while females can simply be “unaffected carriers”. Another way a baby could be born with CNM is through a sporadic mutation, in which there is one CNM-free sperm and one CNM-free egg. The CNM gets into the DNA by one tiny mistake in the copying of the new sperm/egg genes, which will soon form an embryo. This phenomenon is extremely rare. For a detailed diagram of this, see Figure A.

Although central nuclear myopathy was only discovered fairly recently, and not much is known about it, scientists have been able to develop extraordinary medications and therapies for patients. Although there is no known cure for CNM, scientists have discovered what they believe to be the best way to treat it: through treating the symptoms. A current CNM patient, Javad Mashinchi, two-years old, is currently on nine different medications for his treatment of CNM. These medications include: 3, 4 DAP, an experimental drug which helps produce more acetylcholine, Reglan®, helps prevent ulcers, Mestinon®, forces the muscle synapses to accept acetylcholine, Prilosec®, for Acid Reflux Disease, Amoxicillin, antibiotic which helps boost immune system, Robinul®, decreases pulmonary secretions, Albuterol®, decreases lung inflammations, Atrovent®, decreases lung inflammations for a longer period of time, P.E.P. (Positive Expiratory Pressure), prevents lungs from collapsing, and Mask C.P.A.P., which forces the lungs to open. Javad is also currently enrolled in several different therapies, which seem to make life with CNM easier. These therapies include: physical therapy, which helps strengthen muscles and joints, speech therapy, which is used to help patients learn to speak or learn to communicate in another fashion (Javad seems to specially enjoy this class because he gets a chance to communicate through a computer with his mother), and water therapy, which is for physically handicapped, crippled, or extremely weak patients and it gives them an opportunity to move around more than they ever could normally. Although not technically classified as therapies, Javad also takes part in a class called “Early Intervention” and has various nurses come to his house every day to give him personal care.

Everyone has had obstacles to face in life, but most have never experienced anything Javad or any other patients with CNM have been through. Javad has osteoporosis, which causes bones to be very brittle and weak. Javad once fractured his femur, caused by an “unknown etiology”. Another time, Javad was put in a spica cast, which is a cast that goes on both legs, from his ankles up to his naval, to restrict his movement. A few days later, his mother found out that he had broken his knee, caused by the slight jarring of the cast on his leg. Javad has also had tubes put in both ears to help with his recurring ear infections and has been hospitalized 24 times in two years for pneumonia alone. Soon after birth, Javad also received an orchiopexy. An orchiopexy is an operation where the testicles have not descended, so they are pulled back down into the scrotum and fastened there with a “button”.

Central nuclear myopathy, as complex as it sounds, works around only a few different concepts. Early in muscle development, small mononucleate (only one nucleus) cells, known as myoblasts, aggregate and bind themselves together, creating large, multinucleate cells. Inside these cells, known as myotubes, the nuclei are located near the center, and the protein-based machinery required for muscle contraction is not completely formed. Usually, when a myotubes becomes a mature muscle cell, or muscle fiber, the nuclei spread out to the cell’s edges, and the threadlike proteins organize into bunches that provide the force behind muscle contraction. In CNM, some cells in affected muscles appear to be stuck at the myotubes stage of development, interfering with the contraction of the entire muscle. In addition, the brain will not produce enough acetylcholine, which is the substance that causes muscles to contract. The brain releases this substance at the point when one thinks “move the right leg”, so it will travel to the synapses and make them retract, but in CNM, the acetylcholine goes straight through the synapses without the contracting.

Compared to the 25 other boys in the U.S. with CNM, Javad is doing very well. Javad is the only CNM patient in the world without a tracheostomy, a ventilator, or some other type of supported-breathing device. While being only two-years old, Javad is also able to sit up, support his own head, clap, give high-fives, raise and move limbs, and point. Javad enjoys reading, playing with Hot Wheels® cars, taking baths, being held by mom or dad, and watching Pixar® movies (he must have the whole collection!). Javad currently eats 120cc of Pepdite One® three times daily, and 50cc every hour at night for ten hours. He ingests both through a G-tube. If he is able to build up muscle at a constant rate, someday, Javad might even be able to walk with the help of an assistive-walking device.

Although central nuclear myopathy destroys muscle mass, and sometimes even lives, patients that fight for it can almost overcome it. Patients can get strong enough to walk with the support of others, even though when they were first born, they could not even blink. Most CNM patients, weak as they are physically, are much stronger than we are emotionally. They know what could happen to them, and they know that all they can do is keep fighting and work to achieve strength. I believe that if we do not view at these people as “different”, and view at them instead as human beings, just as good as the next person, we could learn something about strength ourselves.

Figure A.  2002 Neuromuscular Disease Project