Connective Tissue Disorders

The Overlaps and Links to Diet

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Contents:

• Overview

• Multiple Occurrences of Rare Connective Tissue Disorders

• Overlapping Features of Connective Tissue Disorders, Including the Marfanoid Body Habitus

• Genes and Connective Tissue Disorders

• Nutrition and Physical Degeneration and Connective Tissue Disorders

• Logic, Cleft Palates and Micrognathia

• Summary

Overview

Interestingly, many features of connective tissue disorders overlap with each other and also with other disorders thought to have unique genetic causes. Geneticists used to believe that most of the connective tissue disorders are caused solely by single genes unrelated to nutrition and unrelated to each other, but are they? What is commonly believed is not necessarily what is true.

There is an ever growing body of evidence that nutrition is a significant factor in many inherited disorders once thought to be caused by genes alone. This seems to be especially true for inherited connective tissue disorders. This section of my site takes a high level view of connective tissue disorders by:

• Making the case that because multiple instances of rare connective tissue disorders seem to occur frequently within a family or even within the same individual, that it is more logical to consider a common denominator as a possible cause than it is to attribute them to genetic coincidence.
• Reviewing the overlapping features and commonalties among different connective tissue disorders and their links to nutritional deficits.
• Exploring how instances of discordant symptoms in identical twins do not logically support the theory of genes as a sole cause of connective tissue disorder syndromes.
• Comparing a number of connective tissue disorder symptoms linked to modern Western diets from the classic nutrition book from the mid 1900s, "Nutrition and Physical Degeneration".
• Reviewing the illogical assumptions about the causes of genetic connective tissue disorders against the background of recent breakthrough studies in nutritional research regarding the birth defects of cleft palates and micrognathia.

Multiple Occurrences of Rare Connective Tissue Disorders

From reading comments on bulletin boards and scanning PubMed, I have read about families with multiple diagnoses of unique inherited connective tissue disorders. For example, I have read about

• A child with Ehlers-Danlos syndrome and a child with Marfan syndrome in the same family
• A child with both Marfan syndrome and Cri du chat (cry of the cat) syndrome (which is really rare)
• A child with Marfan syndrome and a sibling with Fragile X syndrome
• A family with one child diagnosed with both Ehlers-Danlos syndrome and Marfan syndrome

It is interesting to note that both Ehlers-Danlos and Marfan syndromes are each thought to occur in only 1/5,000 people. With this in mind, the odds of someone having both disorders would be .00000004, or pretty close to zero, unless there was some underlying connection between the disorders, such as a nutritional deficiency. So isn't it odd that in the instances above someone has both disorders and in another example there are siblings, one with each disorder. To assume that these closely occurring instances of disorders with similar features are to due to coincidental genetic events is not the most logical consideration. It would be more logical to consider the possibility that there is a common denominator for these closely occurring connections among disorders with similar symptoms.

Because both Marfan and Cri du chat syndromes are also very rare, but share many of the same symptoms, it would be more logical to investigate some common root cause between them as the reason these conditions are found together rather than attributing it to genetic coincidence. From seeing overlaps like these, and in general seeing the wide number of overlaps between the varying connective tissue disorders among family members, it is obvious that the varying degrees of the different symptoms are more like shades of gray rather than black and white, with many people having variations of one or many different connective tissue disorders.

According to a study at Johns Hopkins, more than half of all patients evaluated in their clinic for the possible diagnosis of a heritable disorder of connective tissue could not be determined to have any specifically defined disorder. The authors described these patients as having an "overlap disorder". They suggest that there is a continuum of connective disorder symptoms with mitral valve prolapse at the mild end and Marfan syndrome at the more severe end. This seems like a logical approach that accurately describes what does occur in many families.

Overlapping Features of Connective Tissue Disorders, Including the Marfanoid Body Habitus

The Marfanoid habitus is found in many inherited connective tissue disorders including:

• Marfan syndrome
• Marfanoid hypermobility syndrome
• Osteogenesis imperfecta
• Stickler syndrome
• Beal’s syndrome
• Hypermobility syndrome
• Ehlers-Danlos syndrome
• MVP syndrome
• MASS phenotype
• Shprintzen-Goldberg syndrome
• Homocystinuria
• X-linked mental retardation

and at least 30 more connective tissue disorders listed in the OMIM.

Many of these connective tissue disorders have been given completely unique genetic explanations by medical researchers, however they all share the rather unique Marfanoid body (unusually long arms, legs, finger and toes, pectus excavatum or pectus carinatum, scoliosis) as well as many other overlapping features. It seems illogical to not question why these disorders would all have this very specific and unusual body type in common, plus other features, if they were indeed caused by separate, unrelated genetic events. Why would a single gene control such diverse symptoms as flat feet, sunken chests, blue sclera and mitral valve prolapse? And why would mutations in 30 totally different genes or chromosomes all cause exactly the same features of the distinctive Marfan habitus? Assuming these connective tissue disorders are all caused by unrelated genes or chromosomes leaves some very big unanswered questions.

Listed below are some common features that are symptoms of both connective tissue disorders and nutritional deficiencies. Are the nutritional links coincidences, or are they underlying common causes in a variety of connective tissue disorders? If these connective tissue disorders were all linked through some shared nutritional deficiencies, then there would be perfectly logical reasons for all of the commonalties and overlaps.

Bleeding/bruising tendencies - symptoms of MVP syndrome, Ehlers-Danlos syndrome, Osteogenesis Imperfecta, Hypermobility syndrome, and vitamin K deficiencies.

Blue sclera - Marfan syndrome, Ehlers-Danlos syndrome, osteogenesis imperfecta, and well established indicators for iron deficiency anemia.

Hearing Loss - Ehlers-Danlos syndrome, osteogenesis imperfecta and magnesium deficiencies.

Keratoconus - Marfan syndrome, MVP syndrome, osteogenesis imperfecta, Stickler syndrome, magnesium deficiencies and hyaluronic acid abnormalities. (Hyaluronic acid is generated, in part, from magnesium.)

Hypermobility - MVP syndrome, MASS phenotype, Marfan syndrome, Ehlers-Danlos syndrome, Fragile X syndrome, Hypermobility syndrome, osteogenesis imperfecta, Pierre-Robin syndrome, Stickler syndrome, rickets and alcoholism. (Rickets may be caused by nutritional deficiencies and prolonged alcoholism causes nutritional deficiencies.)

Mitral Valve Prolapse - MVP syndrome, Fragile X syndrome, MASS phenotype, Marfan syndrome, Ehlers-Danlos syndrome, Osteogenesis Imperfecta, Stickler syndrome, homocystinuria, magnesium deficiencies and hyaluronic acid abnormalities.

Micrognathia - Marfan syndrome, Pierre Robin syndrome, Stickler syndrome. Micrognathia occurs frequently with cleft palate, which recent studies show can be prevented in many cases by preconception and prenatal multivitamins with folic acid. Micrognathia and cleft palate have both been produced in animal offspring through maternal diets deficient in biotin. (Biotin is one of the B vitamins, and is a cofactor for folic acid.)

Osteopenia/Osteoporosis - Marfan syndrome, homocystinuria, Ehlers-Danlos syndrome, MVP syndrome, Osteogenesis Imperfecta. Osteopenia and osteoporosis have a wide variety of known nutritional deficiency causes including magnesium and vitamin K deficiencies.

Pectus excavatum, pectus pectus carinatum and scoliosis - Ehlers-Danlos syndrome, homocystinuria, Fragile X syndrome, MASS phenotype, MVP syndrome, osteogenesis imperfecta, idiopathic scoliosis, "isolated" pectus excavatum or pectus carinatum, Stickler syndrome, Pierre-Robin syndrome, and rickets. Rickets may be caused by a wide variety of nutritional deficiencies including calcium, vitamin D and/or magnesium deficits.

Premature births - Ehlers-Danlos syndrome, osteogenesis imperfecta, vaginal infections, magnesium deficiencies and zinc deficiencies.

Fractures - Ehlers-Danlos syndrome, idiopathic scoliosis, osteogenesis imperfecta, hyaluronic acid abnormalities, low estrogen levels and vitamin K deficiencies.

This isn't an exhaustive list, but it does begin to illustrate the commonalities between the different connective tissue disorders. One of my doctors defines a syndrome as "a group of symptoms someone has noticed occurs together, and nobody knows what the hell causes it." What geneticists often fail to see is that just because at one point in time someone noticed a group of symptoms commonly occurring together among family members and gave it a name, then it isn't written in stone and it doesn't mean it has to be solely genetic.

Years ago when many of these genetic disorders were defined, there was little knowledge regarding the nutritional deficiencies that can cause the symptoms of connective tissue disorders. Years ago you couldn't access online databases and run searches looking for logical links - commonalties among the disorders and links to nutritional deficiencies and environmental causes. Today that data is abundant. We know many of the causes of these symptoms, yet for some reason very few people in the medical profession seem to be taking all of this available data and connecting the dots.

I have been diagnosed with multiple inherited connective tissue disorders. I had many of the symptoms listed above, yet I was able to control some of them, such as the easy bruising and mitral valve prolapse, by changing my diet. The book that helped me the most with my diet changes was Super Nutrition for Women. (For a list of all of the top health, nutrition and exercise books that helped me, see my recommended book list.)

Genes and Connective Tissue Disorders

Family members often live in the same house and have similar diets. As such, it is often difficult, if not impossible, to completely determine what traits are influenced solely by genes and what traits are influenced solely by the environment. Many disorders, such as osteoporosis and breast cancer, are known to be influenced by a combination of factors that include both genes and diet. That's why for a variety of chronic health conditions there are many research studies on identical twins. Yet, when it comes to connective tissue disorders, researchers often make the assumption that these disorders are completely genetic, when this conclusion has never been proven.

Attributing any condition occurring among family members who share the same environments and genes solely to either genes or the environment is almost impossible to prove unless you study identical twins reared apart from birth. (And even identical twins shared the same womb and prenatal diet, so you can never really filter out all environmental factors - just the postnatal ones.) That's why the researchers for disorders like breast cancer and osteoporosis do twin studies - to try to separate genetic and environmental factors. Attributing connective tissue disorders solely to genes just because they often do occur in families may be oversimplifying what in reality is likely to a complex set of both genetic and environmental interdependent factors. Diseases such as breast cancer or osteoporosis do often have a genetic component, yet the role of diet is also very important in influencing whether or not one actually develops either disease.

In the 1965 book, "Let's Get Well", nutritionist Adelle Davis recommended that children with the genetic disorder cystic fibrosis (CF) be given a high nutrient diet especially aimed at improving digestion. She felt it was unfortunate that dietary changes were seldom tried for children with cystic fibrosis (in her era) because researchers considered cystic fibrosis to be an "incurable" genetic disorder. Years later, medical research has proved her right. The gene that causes cystic fibrosis was discovered in 1989, however, even among people with the same CF gene there is a very wide range of symptoms, meaning that there are other factors besides genes that influence the course of the disease.

In the last decade, nutritional treatments have been used with success in treating many cystic fibrosis patients. These treatments include high protein-high caloric diets, pancreatic enzymes, and fat-soluble vitamins -- a diet not unlike the one Adelle Davis recommended in her 1965 book. It is unfortunate that it took mainstream medicine so many years to try dietary changes for cystic fibrosis patients. How many other disorders do we have today that are still considered "incurable" genetic disorders simply because the role of diet or other environmental factors has never been adequately considered or explored?

In "Let's Get Well", Ms. Davis writes, "Certain families and individuals have unusually high requirements for one nutrient or another. Often this requirement is 10 to 20 times greater than that considered 'normal'. Such an extraordinary need apparently accounts for many illnesses thought of as hereditary and therefore 'incurable'." Recent research continues to prove Ms. Davis' ideas correct. See my section on Genetic Disorders: The Links to Nutrition for many more examples of disorders once thought to be hereditary actually being caused by unusually high requirements or unusual sensitivities to various nutrients.

As early as 1975, it was observed that identical twins with Marfan syndrome had widely different symptoms. If genes were the only factors in the syndrome, then the twins would be expected to have identical symptoms, since identical twins supposedly have identical genes. In the study link above, the researchers thought the differences among symptoms of the identical twins with Marfan syndrome were "most likely due to the modifying influences of environmental factors". Perhaps both of the girls noted in this study had genes that made them susceptible to Marfan syndrome symptoms, but that variations in their diets or other environmental factors accounted for the differences of the symptoms they actually developed.

In a second case of Marfan syndrome noted in identical twins, it was again noted that the twins had different symptoms. With facts like these, it would be logical to consider that there must be factors other than just genes involved in the disorder, if the genes are thought to be identical yet the symptoms between the twins differ. Something must be triggering the differences. If it isn't entirely the genes, then environmental factors would be the next logical place to look. There is a big difference between having an incurable genetic disorder caused by a single gene, and having a genetic predisposition to develop a given disease that can be mitigated by diet or other environmental factors. I feel that many genetic researchers of today are too quick to assume that connective tissue disorders like Marfan syndrome are caused only by genes, when it has never been proven that diet isn't a factor. Studies on other genetic disorders, like the ones on cystic fibrosis, clearly show that diet often plays an important role, too.

Fragile X syndrome is another connective tissue disorder said to be caused solely by a genetic defect - the absence of the fragile X mental retardation protein. Yet, among identical twins who both have the mutation, one can be normal and one may be affected. If the genes were the sole cause of the syndrome, then one would expect both children to always be affected. Yet, the facts show that this is not always true. If a child has the genetic defect but not any symptoms of the disorder, then this is a pretty good clue that the genetic defect cannot logically be the singular cause of the disorder. If it was the only factor, then everyone with this genetic defect would have the disorder, and everyone with the disorder would have the defect.

As noted above, both Marfan syndrome and Fragile X syndrome have been known to occur together. Both share features of pectus excavatum, pes planus, scoliosis, hypermobility, mitral valve prolapse and dilatation of ascending aorta - all conditions also known to be caused by nutritional deficiencies. Is it random coincidence these conditions occur together, or could they occur together because the people with these disorders have requirements for certain nutrients that are not being met from their diets? The identical twin studies show that genes are not likely to be the singular factor in either disorder, so environmental factors, especially diet, would be a logical area for further research for both syndromes.

Nutrition and Physical Degeneration and Connective Tissue Disorders

The book Nutrition and Physical Degeneration provides some additional clues that nutrition may be a root factor in connective tissue disorders. The author of this book, a dentist named Weston Price, traveled around the world in the early part of the 1900's. He compared the health problems and physical features of people on traditional native diets to people with similar genetic make-ups who had converted to Western diets that included processed foods and refined sugars. His book has detailed comparisons of each diet, pictures of adults and children born and raised on the native diets and pictures of children born and raised after the parents adopted a Western style diet.

On the native diets there were few defects, but for children born and raised under Western style cuisine there is a dramatic incidence of physical defects and health problems. It is interesting to note that many of the defects and health problems of the Western diets are identical to the symptoms of inherited connective tissue disorders. The chart below is a summary I made of the type of features he found on the native diets compared to the features on the Western diets.

Summary of Physical Features
Related to Connective Tissue Disorders Noted in
Nutrition and Physical Degeneration
Before and After the Start of Westernized Diets

This next table takes the symptoms Dr. Price associated with Western diets and nutritional deficits and compares them to the symptoms geneticists today attribute to hereditary connective tissue disorders. Notice that there are a lot of similarities. Entries in the final column note if the features Dr. Price thought were related to poor nutrition have indeed been found in modern studies to be caused to nutritional deficiencies. In many cases, time has proven Dr. Price correct.

Comparison of Western diet features, hereditary connective tissue disorder features and features known to be caused by nutritional deficiencies

Dr. Price didn't know anything about connective tissue disorders when he wrote his book in the mid 1900s. He did, however, have very good logic skills. He knew that if defective physical features were uncommon in people on native diets, but more common in people from the same gene pools on Western diets, then it wasn't likely that the genes were the main factor that were causing the problems. The likely cause was their new Westernized diets.

Based on his observations, Dr. Price was convinced that Down syndrome was caused, at least in part, by a diminished nutritional status of the mother. He based this assumption on two main reasons. His first reason was that he noticed that Down syndrome children had many of the features he believed to be associated with nutritional deficiencies such as underdeveloped jaws and underdeveloped facial features. The second was that he knew that Down syndrome children were more frequently born to older women who had already had many children, and he felt these mothers were at higher risk of being nutritionally depleted. (Actually, many doctors from Dr. Price's era thought maternal nutrition was a factor in Down syndrome. See my section on Genetic Disorders for an interesting excerpt from a 1931 medical book on the suspected cause of Down syndrome.)

Interestingly, recent medical studies have indicated that mothers of children with Down syndrome have an imbalance in folate metabolism. Future studies are anticipated to see if maternal folic acid supplementation will reduce occurrences of Down syndrome, just like they reduced occurrences of spina bifida. If this proves to be true, then Down syndrome, like spina bifida, will become yet another disorder found to be influenced by a combination of both genes and environment (high folic acid genetic requirements mitigated by high dietary folic acid intake), rather than just genes alone.

It is interesting to note that Down syndrome shares many features with connective tissue disorders including micrognathia, underdevelopment of the midface, underdeveloped noses, hypermobility, scoliosis, pectus excavatum, keratoconus, osteopenia and mitral valve prolapse. With this many overlapping features, it would be logical to consider the possibility that unique genetic nutritional requirements may also play a role in connective tissue disorders.

In his book, Dr. Price raises the question: are all of our current problems with birth defects and chronic disorders really just in our genes, or is there a more logical case to be made that the defects are truly in the diets that we are supplying to our genes? Studies in recent years do confirm that many of the features Dr. Price attributed to poor diet have indeed been linked to specific nutritional deficiencies. It is interesting to note that most of these studies were not done until many years after Dr. Price wrote his book, so he would have not been influenced by their results. He had no way of knowing back then that science would prove him right decades after his book was first published.

To help prove his point about the lack of nutrition in Western diets, Dr. Price had chemical analyses performed on both the native diets and the typical American diet of his time period to determine the amount of vitamins and minerals that each one contained. While the average American diet failed to provide even the minimum amount of the U.S. Department of Labor’s standards in effect for that era, the typical native diet provided an average of a four fold increase over the suggested minimums. The native diets varied depending on the local agriculture and animal life, but in all cases the native diets provided higher amounts of all the nutrients tested - calcium, phosphorous, iron, magnesium and vitamins - than the typical American diet. There were dramatic differences in many instances. For example, some of the native diets provided up to 28 times as much magnesium compared to the American diets that were high in processed and canned foods.

More recent studies, done over 40 years after Dr. Price's studies, continue to show that the that many people in the U.S. still do not get the recommended amounts of common nutrients in their diets. A 1993 study done in the U.S. found that "many people in this well-educated, presumably well-nourished population did not consume adequate amounts of calcium, iron, magnesium, and zinc from diet". If many people in our current population are not getting enough of common nutrients in their diets, then it would not be surprising to find a wide variety of health problems related to these nutritional deficiencies, as Dr. Price had surmised from his earlier studies. Perhaps this general lack of adequate nutrition in modern diets, compounded with unique genetic requirements for high amounts of selected nutrients, are both possible factors in connective tissue disorders.

Logic, Cleft Palates and Micrognathia

Micrognathia (underdeveloped jaws) is a feature of Marfan synrome, Ehlers-Danlos syndrome, Pierre-Robin and Stickler syndromes. It is also one of the features frequently mentioned in Dr. Price's book. Being a dentist, one of the main features Dr. Price noticed is that individuals on the native diets had fully formed jaws and straight teeth, while people on the Western diets often had underdeveloped jaws (micrognathia) and crowded teeth. He believed that a diet deficient in nutrients caused a smaller, less developed jaw and dental arch. With a smaller arch, the same number of teeth now had to come out of a shorter space, which explained why the teeth on the Western diets were crowded and overlapped.

A smaller arch would also cause the dental palate to be pushed upward, resulting in a highly arched palate. Crowded teeth, underdeveloped jaws and highly arched palates are common features that today are attributed to hereditary connective tissue disorders such as Marfan syndrome and Ehlers-Danlos syndromes. However, hereditary connective tissue disorders also have many of the the same features as rickets (scoliosis, pectus excavatum, fractures, bowed limbs and osteopenia) and we know rickets is caused by a wide variety of nutritional deficits. If we consider the possibility that a lack of nutrients, perhaps combined with high genetic requirements for certain nutrients, are underlying factors in connective tissue disorders, then there is a perfectly logical reason why people like me with these types of connective tissues disorders frequently have highly arched palates, crowded teeth, underdeveloped jaws, spinal curvature (scoliosis), pectus excavatum, osteopenia, etc.

Today, micrognathia is mentioned in a total of 166 genetic disorders in the OMIM. Out of the 166 disorders in the OMIM in which micrognathia appears, 64 also have cleft deformities as a feature. But what is interesting is that recent studies show that up to 82.6% of the cases of cleft palate can be prevented through preconception and prenatal intake of multivitamins with sufficient folic acid. (Interestingly, folic acid also has been shown to prevent cleft palates in animal studies.) What logical conclusions can we draw from these facts about micrognathia and cleft defects? If micrognathia and cleft palates appear together in 64 disorders, then it simply isn't logical to assume that even though nutrition can prevent the majority of the cases of cleft deformities, that 64 separate genes, unrelated to nutrition, would control the development of micrognathia.

Among identical twins (with identical genes), it has been shown that one may have a cleft deformity and one may not, providing a further clue that genes could not logically be the sole trigger of cleft defects.

The features of cleft palates and micrognathia are likely to be found together because they have shared underlying nutritional deficits as factors. Biotin deficiencies have been shown to produce cleft palates, micrognathia and rib deformities in animal studies. All of these three features are common in connective tissue disorders, so isn't this a good clue that if these same three conditions occur in humans, that perhaps there is also a nutritional deficiency as a root cause, perhaps biotin itself, or a related or dependent nutrient like folic acid? Maybe some of the children who are being diagnosed today with connective tissue disorders just were not getting enough biotin or folic acid in their pre- or postnatal diets to meet their genetic needs.

Summary

It is well established that most of the symptoms of hereditary connective tissue disorders are identical to symptoms of nutritional deficits. Is this a random coincidence, or could nutrition and other environmental factors be a common underlying link in connective tissue disorders? There is a very strong case, repeated again and again and again throughout the various sections of this web site, that nutrition and other environmental factors are likely to be large factors in most connective tissue disorders. There is no logical reason to assume that connective tissue disorders are caused by single genes or even by genetic factors alone.

The book that helped me improve my own health the most with my diet changes was Super Nutrition for Women. (For a list of all of the top health, nutrition and exercise books that helped me, see my recommended book list.)

Related sections of interest:

Links to diet in birth defects and genetic disorders.

Genes may not be the only cause of Marfan Syndrome

Osteogenesis Imperfecta

Diet Help for EDS (Ehlers-Danlos Syndrome)

Pectus Excavatum Causes, FAQ, and Exercises

Could Hyaluronic Acid Help with Aging or Connective Tissue Disorders?

Wrinkled and Dry Skin - What you Eat May Make a Difference

Zinc Deficiency Symptoms