An in depth description...
PMD is caused by a mutation of the Proteolipid Protein Gene (PLP). The PLP gene is located on the X chromosome, so it is generally transmitted from normal appearing carrier mothers to their sons. Because females have two X chromosomes, when there is a gene on one that does not work properly, the other X chromosome generally compensates, so females who carry this defective gene are not usually affected. Each male child born to a carrier mother has a 50/50 chance of being affected with PMD, and each female child born has a 50/50 chance of being a carrier. If a male is not affected with PMD, he cannot pass this disease on to his children. Males with PMD are not likely to have children.
PMD is present at birth, but because the human brain is not fully myelinated at birth, the signs may not become obvious until the child is a few weeks, or even several months old. This is why many PMD children may seem normal at birth and may reach some of the normal milestones that other infants do. But, the PMD child generally plateaus as the non-PMD child continues to progress. During those first few months of life when the nerves fail to become more myelinated (insulated) a PMD child can fall behind their peers in developing normal eye, head, hand and trunk control, this usually causes some concern for the parents and/or doctors.
The first symptom of PMD is usually an involuntary rocking, shaking, or dancing type of movement of the eyes called nystagmus, and is generally noticed between birth and six weeks of age. Some infants may also have stridor (a labored, loud, congested sounding breathing pattern) and in severe cases they may need a tracheotomy. The next symptom is generally a failure to gain normal head and trunk control. They are usually very floppy babies, a condition referred to as hypotonia. PMD children do not gain weight or grow as quickly as other children, even when they consume what seems to be adequate calories. This maybe due to their poor muscle tone, that makes it difficult for them to suck and swallow properly, as well as a possible but unconfirmed metabolic issue that doesn't allow them to absorb nutrients properly. Some PMD children may require a Gastrostomy Tube (G-tube/feeding tube) to supplement nutrition when they cannot, or will not eat or drink enough. PMD children also seem to be more susceptible to infections than their peers. Some other symptoms may be smaller than normal head size, weak or unusual cry, head tremors, poor muscle reflexes, and in rare cases seizures.
As a child with PMD gets older, sometimes their arms and especially their legs become spastic (stiff or rigid). He will usually become uncoordinated or ataxic. Males with this disease may seem to get worse as they grow older, but this is probably due to other things like; poor nutritional health, recurrent infections, skeletal abnormalities (like scoliosis and contractures), growth, maturity and/or seizures. If a male has nystagmus and a past history of this disease the diagnosis can usually be made in the first few weeks or months of life. In families with no past history of PMD the diagnosis is usually made after many other diseases have been ruled out, or when a second handicapped child is born into the family and further investigation is done. An MRI, is generally one of the first tests ordered when neurological delays are noticed in an infant, but in PMD if it is done before one to two years of age, when much of the myelin should be formed, it may offer a false assurance that the child does not have PMD.
The definitive test for PMD is the detection of a genetic mutation in the PLP gene. The mutation may be inherited or may happen spontaneously. Genes are carried on chromosomes. The chromosome can be thought of like a bookcase and the gene as a book located on the bookcase. DNA, which is the basic component of the gene, is like the letters in the book. Genetic information is stored and passed down from generation to generation, in the form of the precise sequence of DNA letters or bases.
In PMD various mutations within this gene have been identified. The types of mutations that are known to cause PMD fall into two general categories: point mutations and duplication's. A mutation (any alteration of the DNA) that affects only a single base (one letter) is called a point mutation. Other types of mutations can occur as well, including insertions (additions of DNA into a gene), deletions (removal of part of a gene) and duplication's where entire genes are present in one or more additional copies.
In the less severe cases of PMD males speak in a slow drawn out manner. They may have a vocabulary of a few simple words or phrases, or an extensive list of several thousand words. They may sit with minimal support, maneuver their own wheelchair, feed themselves finger foods (or small pieces with a spoon or fork), handle a covered cup, and be toilet trained. Rarely some mildly affected individuals may learn to walk, with minimal assistance or support. In the most severe cases males never develop any real physical or self help skills, they are unable to sit without total support and are unable to feed themselves or talk. They do seem to understand words and concepts though even when unable to speak. They are also more medically fragile. Because of their limited physical abilities many PMD males are labeled severely retarded, but parents and individuals who take the time to get to know these children, know that they understand much more than they are able to express. They are very amazing in their ability to use their limited and/or abnormal body movements to do things that seem impossible for them. Schooling varies from place to place. Some PMD males may learn colors, letters, words, and numbers. If the teacher is receptive to having them in the classroom and he/she is creative they may do very well. In other cases the children are often lost in the shuffle and school is nothing more than a "babysitting" service. But with computers and new technology these children may someday be able to show us all how intelligent they really are. Life expectancies seem to vary depending on how severely affected the male is. Some patients live only a few months or years, while others may live into their sixties. In families with a past family history of this disease, affected males are generally affected similarly in abilities and life expectancies. However, even within a family where we know that all the affected individuals have the same mutation, there can be variations in the severity of symptoms. PMD does not exclude a child from having other issues related to genetics, cleft lip/palate, cardiac problems, or traumatic birth issues like prematurity, meconium aspiration, Cerebral Palsy (CP), infections, etc.
Unfortunately, there is no specific treatment for PMD as yet, so treatment is purely symptomatic. Progression of physical deformities may be slowed by appropriate physical and/or occupational therapy. Good nutritional health can be more difficult. Most PMD infants are able to take feedings by mouth; they sometimes have difficulty sucking due to their weak muscle tone and/or a high palate (roof of the mouth). Most do eventually enjoy eating and usually handle solids easier than liquids. However, some do require nasogastric (NG) or gastronomy tube (G-tube) feedings to supplement or provide nutrition when they cannot or will not eat properly. Research in genetics is progressing very quickly, but for those waiting for answers it seems very slow. We hope in the near future, they will be able to find the gene mutation for all PMD families. Then they will be able to diagnose these males accurately, tell if a female is a carrier before she has an affected child, and determine prenatally, if a child will be affected with, or be a carrier of PMD.
Thanks to advancements in medical care and medications everyone is living longer these days. We cling to this, and hope the same will be true for our PMD boys. There is research being done that we hope will eventually lead to better treatments and possibly even a cure for PMD, but for today we continue to offer support and encouragement to the families with PMD children.
PMD is caused by a mutation of the Proteolipid Protein Gene (PLP). The PLP gene is located on the X chromosome, so it is generally transmitted from normal appearing carrier mothers to their sons. Because females have two X chromosomes, when there is a gene on one that does not work properly, the other X chromosome generally compensates, so females who carry this defective gene are not usually affected. Each male child born to a carrier mother has a 50/50 chance of being affected with PMD, and each female child born has a 50/50 chance of being a carrier. If a male is not affected with PMD, he cannot pass this disease on to his children. Males with PMD are not likely to have children.
PMD is present at birth, but because the human brain is not fully myelinated at birth, the signs may not become obvious until the child is a few weeks, or even several months old. This is why many PMD children may seem normal at birth and may reach some of the normal milestones that other infants do. But, the PMD child generally plateaus as the non-PMD child continues to progress. During those first few months of life when the nerves fail to become more myelinated (insulated) a PMD child can fall behind their peers in developing normal eye, head, hand and trunk control, this usually causes some concern for the parents and/or doctors.
The first symptom of PMD is usually an involuntary rocking, shaking, or dancing type of movement of the eyes called nystagmus, and is generally noticed between birth and six weeks of age. Some infants may also have stridor (a labored, loud, congested sounding breathing pattern) and in severe cases they may need a tracheotomy. The next symptom is generally a failure to gain normal head and trunk control. They are usually very floppy babies, a condition referred to as hypotonia. PMD children do not gain weight or grow as quickly as other children, even when they consume what seems to be adequate calories. This maybe due to their poor muscle tone, that makes it difficult for them to suck and swallow properly, as well as a possible but unconfirmed metabolic issue that doesn't allow them to absorb nutrients properly. Some PMD children may require a Gastrostomy Tube (G-tube/feeding tube) to supplement nutrition when they cannot, or will not eat or drink enough. PMD children also seem to be more susceptible to infections than their peers. Some other symptoms may be smaller than normal head size, weak or unusual cry, head tremors, poor muscle reflexes, and in rare cases seizures.
As a child with PMD gets older, sometimes their arms and especially their legs become spastic (stiff or rigid). He will usually become uncoordinated or ataxic. Males with this disease may seem to get worse as they grow older, but this is probably due to other things like; poor nutritional health, recurrent infections, skeletal abnormalities (like scoliosis and contractures), growth, maturity and/or seizures. If a male has nystagmus and a past history of this disease the diagnosis can usually be made in the first few weeks or months of life. In families with no past history of PMD the diagnosis is usually made after many other diseases have been ruled out, or when a second handicapped child is born into the family and further investigation is done. An MRI, is generally one of the first tests ordered when neurological delays are noticed in an infant, but in PMD if it is done before one to two years of age, when much of the myelin should be formed, it may offer a false assurance that the child does not have PMD.
The definitive test for PMD is the detection of a genetic mutation in the PLP gene. The mutation may be inherited or may happen spontaneously. Genes are carried on chromosomes. The chromosome can be thought of like a bookcase and the gene as a book located on the bookcase. DNA, which is the basic component of the gene, is like the letters in the book. Genetic information is stored and passed down from generation to generation, in the form of the precise sequence of DNA letters or bases.
In PMD various mutations within this gene have been identified. The types of mutations that are known to cause PMD fall into two general categories: point mutations and duplication's. A mutation (any alteration of the DNA) that affects only a single base (one letter) is called a point mutation. Other types of mutations can occur as well, including insertions (additions of DNA into a gene), deletions (removal of part of a gene) and duplication's where entire genes are present in one or more additional copies.
In the less severe cases of PMD males speak in a slow drawn out manner. They may have a vocabulary of a few simple words or phrases, or an extensive list of several thousand words. They may sit with minimal support, maneuver their own wheelchair, feed themselves finger foods (or small pieces with a spoon or fork), handle a covered cup, and be toilet trained. Rarely some mildly affected individuals may learn to walk, with minimal assistance or support. In the most severe cases males never develop any real physical or self help skills, they are unable to sit without total support and are unable to feed themselves or talk. They do seem to understand words and concepts though even when unable to speak. They are also more medically fragile. Because of their limited physical abilities many PMD males are labeled severely retarded, but parents and individuals who take the time to get to know these children, know that they understand much more than they are able to express. They are very amazing in their ability to use their limited and/or abnormal body movements to do things that seem impossible for them. Schooling varies from place to place. Some PMD males may learn colors, letters, words, and numbers. If the teacher is receptive to having them in the classroom and he/she is creative they may do very well. In other cases the children are often lost in the shuffle and school is nothing more than a "babysitting" service. But with computers and new technology these children may someday be able to show us all how intelligent they really are. Life expectancies seem to vary depending on how severely affected the male is. Some patients live only a few months or years, while others may live into their sixties. In families with a past family history of this disease, affected males are generally affected similarly in abilities and life expectancies. However, even within a family where we know that all the affected individuals have the same mutation, there can be variations in the severity of symptoms. PMD does not exclude a child from having other issues related to genetics, cleft lip/palate, cardiac problems, or traumatic birth issues like prematurity, meconium aspiration, Cerebral Palsy (CP), infections, etc.
Unfortunately, there is no specific treatment for PMD as yet, so treatment is purely symptomatic. Progression of physical deformities may be slowed by appropriate physical and/or occupational therapy. Good nutritional health can be more difficult. Most PMD infants are able to take feedings by mouth; they sometimes have difficulty sucking due to their weak muscle tone and/or a high palate (roof of the mouth). Most do eventually enjoy eating and usually handle solids easier than liquids. However, some do require nasogastric (NG) or gastronomy tube (G-tube) feedings to supplement or provide nutrition when they cannot or will not eat properly. Research in genetics is progressing very quickly, but for those waiting for answers it seems very slow. We hope in the near future, they will be able to find the gene mutation for all PMD families. Then they will be able to diagnose these males accurately, tell if a female is a carrier before she has an affected child, and determine prenatally, if a child will be affected with, or be a carrier of PMD.
Thanks to advancements in medical care and medications everyone is living longer these days. We cling to this, and hope the same will be true for our PMD boys. There is research being done that we hope will eventually lead to better treatments and possibly even a cure for PMD, but for today we continue to offer support and encouragement to the families with PMD children.
