Tag: Irvin Rosenfeld

Ballyhanna Man – Early Evidence of Hereditary Multiple Exostoses in Ireland

He occupies pride of place in a specially constructed case at Donegal Museum in Letterkenny in far-flung rugged North West Ireland, and was a key focus of the Ballyhanna Research Project funded by Ireland’s National Roads Authority (NRA) and involving cross-border collaboration between Queen’s University Belfast and the Institute of Technology in Sligo.

Dating at least 600 years, from 1100-1400, ‘Ballyhanna Man’ was one of 1,200 skeletal remains found by archaeologists around a buried church less than a mile south of Ballyshannon, on the banks of the River Erne, in 2006.

And what makes him so interesting is that he is the first intact case of Hereditary Multiple Exostoses (HME) / Diaphyseal Aclasis to have emerged in Irish archaeology and one of the very few in the world.

Research (which is ongoing) evidence so far indicates he was a young adult of about 25 years old when he died (typical of the mortality rate of the other non-HME male remains excavated at the burial site). Projecting bony lumps were evident on the upper and lower limbs: Two bones on each lower leg were fused together, and he was knock kneed. His arms were bow-shaped, with the left arm noticeably shorter.

Ballyhanna Man’s condition would have meant he suffered from pain and was very much disabled, and yet it is unlikely he would have survived to such an age without some form of support.  He appears to have been afforded the same Christian burial as other remains. Regarding his quality of life, given he would have had HME since childhood, who knows?

Given the congenital nature of HME, osteoarchaeologists are working to establish family ties between Ballyhanna Man among the other remains. The remains of a second, man, young to middle aged adult in his late 30’s to 40’s, exhibiting lumps that would have been less obvious than those which afflicted Ballyhanna Man, were also excavated in the same burial ground. According to researchers radiocarbon dating indicates he died several hundred years before Ballyhanna Man, which may point to the HME gene existing within the group for a considerable period of time.

The hope is that in future advancements in genetics and DNA research will provide evidence regarding how HME has evolved.

[Source / read more: Early evidence of Hereditary Multiple Exostoses (HME) in Ireland]

In addition to the two skeletal remains uncovered by archaeologists at Ballyhanna, two skeletal remains with indications of HME were uncovered by archaeologists in Dublin: The remains of a young to middle-aged female were excavated from a medieval cemetery on St. Stephen’s Street, while a young adult male, dating back to later early Christian era, was exhumed in Kilshane.

In the study of ancient diseases that is paleopathology four of the 16 known cases of HME are specific to Ireland, and a further three cases specific to England (the remaining nine ancient cases of HME are located in Jordan, Zimbabwe, Peru, Sweden, Poland and Canada). As such, is living on an isolated island in any way significant in the context of a higher HME prevalence in the UK and Ireland?

The purpose of this blog (updated June, 2019) is to provide a focal point of support and information for family members and persons living in Ireland and beyond who have Hereditary Multiple Exostoses (HME) in order to encourage them to share their experiences so that people in general will have a clearer understanding of this rare condition and how challenging affected lives can be.

While I appreciate many of us are reluctant to open up about such a personal concern, after reading my account of HME and Me, for all one knows you will be roused to introduce your own personal experiences, questions and feedback in the “Comments” https://nialljoreilly.com/2012/04/28/hereditary-multiple-exostoses-ireland/#comments piece located at the bottom of this paper.

Contents:

• Ballyhanna Man – Early Evidence of Hereditary Multiple Exostoses in Ireland
• HME and Me
• What is Hereditary Multiple Exostoses?
• Prevalence and geographical reach
• Bony lump?
• What complications are caused by HME?
• Congenital?
• What are the chances of transmitting HME to your children?
  • Pre-Implantation Genetic Diagnosis (PGD): Karyomapping and MALBAC
• Treatment
• Pain Management
• Medical Marijuana
• Traditional Chinese Medicine (TCM)
• Omega-3 Krill Oil
• Homeopathy
• Prognosis – The Good News
• HME and Autism / Asperger Syndrome linkage? 
• HME and animals?
• Bone-lengthening surgery
• Dorsal Foot Exostosis
• Is that a bunion or exostosis protruding from your foot?
• Orthopaedic / Neurological  Consultant / Surgeon HME Knowhow in Ireland
• Support resources for HMEers and their families
• HME Research 
• Comments (64)

HME and Me

I recall being about nine years old, maybe younger, when I first noticed the large tender lump protruding from my left shoulder blade like a Rhino horn. I soon became very self-conscious as bone protrusions multiplied to cover my legs (femur, tibia, and fibula), arms (humerus, radius, and ulna), shoulder blades, hands, feet, ribs, and pelvis, particularly around the shoulder, elbow, wrist, knee, and ankle joints. My height was affected, as was the shape of my arms (bow-shaped, my left arm is shorter than my right) and legs (my knees won’t bend all the way), with structural impairment to my left elbow and hand. I knew I was different to all my other friends, and with such low self-esteem I certainly felt that way. I hated going to school. I just wanted to seclude myself. As a consequence I was shy and introverted as a child.  I wore long sleeve shirts and explained away the bow-like curvature of my left arm by faking how it had been broken. I loved sports, but was unable to participate like other kids my age, while almost nobody, except my mother, knew of the constant 24*7*365 daily pain, the cause of which medical practitioners in the 1970s and 1980s were at a loss to deduce.

The surgery started in earnest back in 1976 when I was 13 years old, the last procedure I underwent was earlier this month (June 2019). All told I have endured numerous operations in which at least 51 and a half of the more irritating bone tumours have been hacked, sawed, and chiseled off. The leading orthopedic surgeons in Ireland in the 1970s, 80s, and 90s, Messrs. Gerry “Gold Fingers” Brady, John Varian, and Jimmy Sheehan all had a go on me in both Saint Michael’s Private Hospital, in Dun Laoghaire, and the Mount Carmel Hospital, over in Churchtown (Dublin).

Most recently in November 2018 and April 2019 specialist orthopediac surgeons Philip Grieve and Hannan Mullett carried out surgical procedures at the Blackrock Clinic in South Dublin, while in June 2019 orthopediac surgeon Alan Laing also operated on me at the Blackrock Clinic.

In addition, over the years, I have also been referred to orthopedic consultants, ENT consultants, neurologists (medical interns in tow) and Traditional Chinese Medicine (TCM) practitioners in Liverpool (UK), Seoul (Korea), Singapore, Malaysia, Hong Kong and mainland China.  

In 1990, following an operation to remove a benign tumour from the bone surface of my pelvis, I recall the surgeon’s reassuring words “That’s it, no more operations, the bony lumps wouldn’t grow again“, and that I could now get on with my life. I was 27 years old and I’d gone through more operations, physiotherapy, and recovery periods and overcome more obstacles than anyone should ever have to go through in their entire life. So get on with my life I certainly tried to do, and did. 

However, despite leading as active a life as I could, the ever present twinge, spasm, ache, and clicking sound, which I guess only a person with HME can truly identify with, continued and in 2008 I was referred to neurologist Mr. Chris Pidgeon at Dublin‘s Beaumount Hospital. He advised surgery on compressed cervical vertabra caused by atypical spinal curvature on the basis that if I didn’t have such surgery sooner rather than later nerve damage and dysfunction would gradually lead to acute lack of sensation on the left side of my body. At around the same time one of China‘s leading ENT experts, Professor Pu Xing Kuan (JiangSu Province Hospital, Department of Oto-Rhino-Laryngology -卜行宽, 江苏省人民医院耳鼻咽喉科卜行宽主任医师) postulated a connection between the bony growths and troubling hearing and balance challenges.

New medical knowledge gleaned through advances in scientific research indicate that intermittent fatigue, poor coordination and short concentration span troubles I have always tried to come to grips with are neurological motor disorder symptoms associated with HME, and not just a figment of my imagination.

Roll on to 2018 / 2019 and the most recent operations have involved cubital tunnel surgery on my elbow, the removal of an exostosis embedded deep under my scapula, which the surgeon described as akin to “looking for a needle in a haystack“, and Hallux Valvus (Latin: deformed foot) surgery on my right foot. Following this latest operation, I am hoping the removal of two and a half exostoses and the insertion of a titanium implant will lead to pain-free mobility. Next up will be operations on my left foot, lower right arm and left hand, hopefully by all over by the end of 2019.

In terms of recovery: Truly amazed about the impact the surgery has had on my left elbow. Fully healed or me the outcome has been perfect. It is only two months since the surgery on my scapula, and why I feel the healing is slower various physiotherapists have noted that scapula / shoulder related surgery is notorious for the time it takes to fully heal.

Developments in medical science and technology over the past 10 years have been incredible, enabling surgeons to perform procedures that wouldn’t have been risked without such advancement. 

By and large living with HME has been a silent battle marked by good and bad days. Sometimes I want to climb to the top of a mountain and scream. Most times I just grin and bear it. To everyone else I look normal. Nobody has a clue what I deal with on a daily basis. Unfortunately, while the bad days don’t define me, they are happening more often than I care to admit, affecting every aspect of my life, including my mobility and career. Now I would describe a good day as a day when pain is manageable, when the level of needling, throbbing, pain is at least two levels below my average, which according to the Universal Pain Assessment Tool chart posted below is at least Level 7.5. Consistent pain and related anxiety have also led to bouts of really bad depression. However, I always seem to pick myself up and move on.

In spite of the challenges that come with the territory, I would never let HME beat me, and so over the past year, after dithering way too long, I have been engaged with a truly amazing team of world-class shoulder, elbow, hand, wrist, foot, ankle, hip, knee, neurosurgery, neurophysiology consultants at the Blackrock Clinic (scroll down to ‘Orthopedic / Neurological Consultant / Surgeon HME Knowhow in Ireland’ for more information about specific consultants) pinpointing the most pressing HME-related problems via SPECT CT scams, MRIs, x-rays, and nerve conduction tests with the aim of correcting them now. No more delays on my part. A few more operations to go, but hopefully all done by the end of the year.

What is Hereditary Multiple Exostoses?

The condition was first alluded to in 1786 by John Hunter, the prominent, yet controversial, Scottish surgeon and anatomist, infamously known for taking possession of 2.31 metres tall Irish giant Charles Byrne’s corpse contrary to Byrne’s clear deathbed request. It would take a further 90 years  for the term ‘multiple exostoses’ to first surface, as conceived in 1876 by the venerated German physician Rudolf Virchow. What is more, the first reference to Hereditary Multiple Exostoses (HME) in American medical literature only happened in 1915 when the Boston surgeon Albert Ehrenfried wrote of “Multiple cartilaginous exostoses—hereditary derforming chorodysplasia: A brief report on a little know (sic) disease”.

Hereditary Multiple Exostoses (HME) [one of the numerous synonyms  along with: Bessel-Hagen Syndrome; Chondral Osteogenic Dysplasia of Direction; Chondral Osteoma; Deforming Chondrodysplasia; Diaphyseal Aclasis (multiple hereditary); Dyschondroplasia; Exostosing Disease; Exostotic Dysplasia; Exostosis Multiplex; EXT; Hereditary Deforming Chondrodysplasia; Hereditary Multiple Osteochondromas; Multiple Cartilaginous Exostoses; Multiple Congenital Osteochondromata; Multiple Exostoses; Multiple Hereditary Exostoses (MHE); Multiple Hereditary Osteochondromatosis (MHO); Multiple Osseous Exostoses; Multiple Osteochondromas (MO – which is the term designated by the World Health Organisation (WHO)); Multiple Osteomatoses; Osteochondromatosis; and Osteogenic Disease] is a very rare bone disease  in which multiple benign bony cartilage-capped outgrowths (or exostoses / osteochondromas) that are atypical in size, position and number grow in areas of active bone development, or open growth plates, in children. 

Regarding HME’s origins scientists have linked it with chromosomal mutations in three genes:  EXT1, which maps to Chromosome 8q24.1; EXT2 which maps to Chromosome 11p13;  and EXT3 which maps to the short arm of Chromosome 19 (though its precise location is still unclear). It seems the majority of HME cases have either HME EXT1 or HME EXT2 mutations, while a small proportion of HME cases are linked to the EXT3 gene.

• Approximately 50% of people with HME are diagnosed by the time they are three years old

• 5% of newborns that carry an HME gene show some signs at birth

• Though not present at birth, 96% of all cases with HME will show noticeable signs by the time they are 12 years old

• Approximately 70% of people with HME have an exostosis or bone abnormality around the knee

• Six is the number of exostoses the average person affected with HME will typically develop during his or her life

• Most often affected are long tubular bones, while in 10% of cases the small bones of the hands and feet are also affected, the scapula only in 1% of patients. The spine is involved only in 2%, but it can lead to cord compression.

While HME currently has no cure, the good news is that a cure may not be far away!

HME NEWS FROM 2018

MHE Research Foundation in collaboration with Clementia Pharmaceuticals announced recruitment for the trialing in Australia, Belgium, Canada, France, Italy,  Japan, Portugal, Spain, The Netherlands, Turkey, United Kingdom and United States ) of (once daily pill) the efficacy and safety Clementia Palovarotene, as a potential treatment of HME in children.

Source: https://www.mherf.org/clementia-drug-trial

Latest HME Research Paper 2018 – Palovarotene Inhibits Osteochondroma Formation in a Mouse Model of Multiple Hereditary Exostoses (Toshihiro Inubushi, Isabelle Lemire, Fumitoshi Irie, and Yu Yamaguchi)

Research moves toward the first drug treatment for Hereditary Multiple Exostoses

Prevalence and geographical reach

Curiously, the research also points to much higher prevalence rates amongst island populations with geographically restricted movement, such as Guam, which has about 100 HME cases per 100,000 people.

Be that as it may, taking for granted that Ballyhanna Man, and the two age-old skeletal remains discovered in Dublin, proved HME’s existence in Ireland over 600 years ago one would be inclined to think that given its hereditary nature the prevalence of HME among their future ascendants on the island would be relatively high. In actuality, secondary research and interactions with orthopaedic surgeons and online support groups undertaken by myself suggest there are about 120 cases on the island of Ireland (May, 2019).

Geographically, while the primary HME clusters are to be found in Europe, North America, and Australia, HME is a global bone disease with people impaired by the condition living in China, India, South East Asia, South America and Africa.

Chloe B tells the story behind the scars

Bony Lump?

An exotosis is a benign rounded or sharp bone growth at the metaphyseal areas of the long bones. Exostoses start, and continue, growing, for the duration of a child’s development around the growth centres of bones that are near the ends of the bones, which is why lumps tend to grow, or fuse, near the joints. When a person has achieved full skeletal growth, the exostoses are expected to stop growing, which is not to say their tenderness also stops. This last point is quite contentious, as previously less painful exostoses can become very tender with the wear and tear of age. Moreover, exostoses can also return to the same places from where lumps have been previously extracted, and they may be more painful. Many members of online HME support communities highlight increasingly chronic pain experienced in later life.

What is an Osteochondroma?

Chronic, not contagious

What complications are caused by HME?

HME can be particularly troublesome. Because the exostoses grow around areas of active bone growth, they disrupt the normal growth process, leading to defective growth that causes nerve compression, inequality of limb length and irritation of adjoining soft tissue, such as skin, nerves, tendons, muscles, and blood vessels. Such is their sensitivity, these cartilage-capped lumps can cause chronic pain, clicking sounds,  and numbness until they are surgically removed. Accidentally bumping them against something solid can be particularly painful.

Exostoses that grow near the ends of long bones may limit the normal range of motion of the joints upon which they encroach. Consequently, people with HME may have a shorter stature than average, with studies of HME patients showing the final height in men typically averaging 170 cm (66 in), while the average height in women is about 160 cm (62 in). Moreover, differential rates of growth between a child’s legs or arms can result in disparities in leg or arm length sometimes reaching 2 cm (1 in) or more. Leg length disparity can result in hip pain and difficulties with walking caused by a slanting of the pelvis.

HME patients may also have bowed arms or legs. Often, the forearm will bow out, or the legs can grow to be “knock-kneed“. While function is usually  fairly normal, the bowing can be very troublesome.

Another complication caused by HME is stiffness, particularly in the hands, elbows and hips usually because the lumps block their natural movement. 

The most alarming potential HME complication is also one of the rarest, typically occurring after skeletal growth has finished. In less than 1% of cases the benign exostoses can become a cancerous tumor called Chondrosarcoma, aka ‘Sarcoma‘. Such Chondrosarcoma cases are usually in the 20’s to 50’s age range. Growth and soreness are two key warning signs that a benign tumor has become malignant. If a person with HME notices after they have stopped growing that an exostosis is getting larger or painful he or she should consult their doctor right away.  Chondrosarcoma while uncommon (arising in 0.5% to 3% of HME patients) is still something people who have Hereditary Multiple Exostoses must know about. An unnoticed bone malignancy always presents a risk of metastasis (the spreading of cancerous cells elsewhere in the body), which is one of the most dangerous complications of any cancer (For more on Sarcoma check out this YouTube video explanation from Dr. Christopher R. Beauchamp, M.D., Orthopedic Oncology and Adult Reconstruction Surgery, Mayo Clinic ).

Congenital?

Hereditary Multiple Exostoses (HME) [Multiple Hereditary Exostoses (MHE), Hereditary Multiple Osteochondromas, Multiple Exostoses, Exostosis Multiplex, Multiple Osseous Exostoses, Multiple Cartilaginous Exostoses], or Diaphyseal aclasis is a condition that is passed by the genes of the affected parent to their children. If one parent has the condition, there is a 50% likelihood that any child could also develop Hereditary Multiple Exostoses (HME).

As is my own situation, in 10% to 20% of HME cases a person can develop multiple exostoses with no family history of HME. In medical terms this is referred to as a de novo or “spontaneous mutation” indicating a genetic problem arose in that person without being inherited from a parent.  Moreover, my two brothers, who are both in their 60s, did not inherit this condition.

HME has a 96% penetrance, which means that if the disease is indeed transmitted to a child, he or she will have a 96% chance of actually manifesting the disease, and 4% chance of having the disease but never manifesting it.

While males who have the HME gene tend to exhibit more obvious and severe symptoms than females, and are therefore more likely to be diagnosed with HME, males and females are equally likely to inherit HME.

Straight talking exostoses boy Mikey spells it out in black and white

What are the chances of transmitting HME to your children?

A person with HME has a 50% chance of transmitting this condition to his or her children.  Male and female are equally likely to be affected. In other words, if it is assumed that four children are produced, and one parent is a carrier and exhibits the disease, the statistical expectation is for two children to be normal and two children to inherit this disease. This does not mean that children will necessarily be affected; it does mean that each child has a 50:50 chance of inheriting the disorder.

Pre-Implantation Genetic Diagnosis: Karyomapping and MALBAC

For individuals with HME who are considering starting a family, recent scientific developments in pre-implantation genetic screening and diagnosis (PGS & PGD) and pre-natal diagnosis can detect the exostoses gene from embryo samples and help select normal embryos. [Note: For further information about PGS refer to the ‘Research’ section below].

In Ireland the first pre-implantation genetic diagnosis pregnancy in late 2013 was hailed by the Cork Fertility Centre (www.corkfertilitycentre.com) as a “major breakthrough”. [Source: Irish Times 3rd November 2013 http://www.irishtimes.com/news/ireland/irish-news/first-pregnancy-in-ireland-using-new-screening-technique-1.1582427].

In February 2015, confirming the significance of pre-implantation genetic diagnosis with respect to detecting the exostoses gene the Cork Fertility Centre , stated:

“We do provide PGD service for Multiple Exostoses patients based on Karyomapping technic, which can do the same job as MALBAC. Karyomapping can detect the exostoses gene from embryo samples and at the same time obtain the information of chromosome status. ” (Source: Cork Fertility Centre email to author of this blog piece, dated 15th February, 2015).

The Beacon CARE Fertility centre in Sandyford, Dublin, also provides pre-implantation genetic testing services.

HME NEWS FROM 2014

“Hereditary Multiple Exostoses patients can now expect their offspring to be free from their disorders”

Beijing (Peking) University, Sep.24, 2014: On September 19, 2014, the first in vitro fertilization (IVF) baby with pre-implantation genomic screening based on MALBAC was born in the Beijing University Third Hospital, Beijing, China. MALBAC is a newly developed whole genome amplification method, allowing for the precise selection of embryos in the IVF process when combined with next generation sequencing. This event brings the good news to patients with monogenic diseases around the world that they can now expect their off springs free from their disorders.

In this case, the husband suffers from Hereditary Multiple Exostoses, an autosomal dominant hereditary disorder, which is characterized by multiple bony spurs or lumps on the bones at an early age. There is a frame-shift point mutation at the EXT2 gene of this patient, which has a 50% chance of transmitting this disorder to his children. To avoid this risk, a normal embryo free from the husband’s disease allele was selected by Dr. Jie Qiao’s group at Beijing University Third Hospital using the MALBAC technique that was developed by Sunney Xie’s lab.  

Total 18 embryos at blastocyst stage were obtained from the couple during IVF cycle, and a few cells were biopsied from each of the day 5 or day 6 embryo. Genomic DNAs of the obtained cells were amplified evenly and accurately with the MALBAC method for the whole genome sequencing analyses. Combined with the targeted PCR and next generation sequencing techniques, all the numerical and structural chromosome abnormalities and the mutated allele of the genetic disease were accurately detected with low depth sequencing data (0.1X). The team identified three embryos with neither the inherited mutated allele nor chromosome copy number abnormalities from these 18 embryos, and finally chose one healthy embryo to transfer back to the wife. The embryo implanted successfully, grew normally, and later the amniotic fluid cells from the baby were isolated and analyzed as free of aneuploidy and mutated allele. Now the baby was born successfully, with 4.03 kg of weight and 53 cm of length. Umbilical cord blood genome detection confirmed the baby is free of the mutated allele.

Pre-implantation genetic diagnosis (PGD) is a technique that helps selecting normal embryos to transfer into uterine using IVF. It is an early prenatal diagnosis technology to obtain a healthy offspring by avoiding the genetic diseases.

Currently, the widely used PGD technologies are fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), and comparative genomic hybridization (Array-CGH) and single-nucleotide polymorphism (SNP-array)… it has been highly desirable, but has not yet been reported to simultaneously detect monogenic point mutations and chromosome abnormalities. MALBAC allows for simultaneous circumvention of point mutations and chromosome abnormalities with high accuracy. Furthermore, the procedure developed by the team has used low depth sequencing, allowing low cost and fast PGD.

MALBAC, a powerful single cell whole genome amplification method, which was first developed and reported by Sunney Xie’s lab in 2012, is the key technique in this project. Since MALBAC use linear instead of exponential amplification, it is much more accurate and uniform than the traditional DOP-PCR and MDA methods. So MALBAC can be used to analyze the genomes of rare and limited materials. At the end of 2013, Sunney Xie’s lab cooperated with Jie Qiao’s team and Fuchou Tang’s lab and demonstrated the proof of principle of using MALBAC for PGD in IVF, which was published in Cell.

The project is done with the support from the Ministry of Science and Technology, Beijing Municipal Science and Technology Commission, the National Natural Science Foundation of China, and 985 project of Peking University. The project is accomplished under the cooperation of the three partners: Jie Qiao’s team in Peking University Third Hospital, Sunney Xie’s lab and Fuchou Tang’s lab in Biological dynamic Optical Imaging Center (BIOPIC) of Beijing University.

Source: Peking University Third Hospital at http://english.pku.edu.cn/News_Events/News/Research/11626.htm.

Ruby Page explains what it’s like to live with HME

Treatment

Some people with HME never need any treatment. They learn to counterbalance the abnormality or reduced range of motion so they can perform as normally as possible. When abnormality does occur it often develops so slowly that the patient can adjust to it well, while others may require surgical treatment to provide relief.

Surgery (bear in mind modern medicine has really advanced with ongoing technological breakthroughs!), physiotherapy and pain management are currently the only options available to HME patients, and while success varies from patient to patient many continue to struggle with pain, fatigue and mobility problems throughout their lives.

It is not unusual for patients with Hereditary Multiple Exostoses (HME) [Multiple Hereditary Exostoses (MHE), Hereditary Multiple Osteochondromas, Multiple Exostoses, Exostosis Multiplex, Multiple Osseous Exostoses, Osteocartilaginous Exostoses, Multiple Cartilaginous Exostoses], or Diaphyseal aclasis to undergo numerous surgical procedures throughout their lives to remove painful or deforming exostoses, correct limb length discrepancies or improve range of motion.

HME Presentation by Dr. Dror Paley, Paley Limb Lengthening Institute, St. Mary’s Hospital, West Palm Beach, Florida

If an exostoses is painful, pressuring an important structure, visibly unsightly, or is easily knocked, it can be removed by surgical methods. Excision itself is usually a fairly straightforward procedure, some are removed without necessitating an overnight stay in hospital. Once removed, however, as previously mentioned, exostoses can reappear (about 20% – 50% of the time), although they are may not grow to the same extent as before. 

When an exostosis causes a growth deformity, such as bowing, sometimes simply cutting off the lumps at an early stage will let the bone straighten itself out and adapt as the child grows. However, some bowing is so acute that not only must the lumps be removed, but also the bone must be straightened. This can be done either by cutting the bone, remodeling it and then holding it in place while it mends or, if the child is still developing, by altering the rate of growth on one side of the growth plate.

There are a number of options available and an orthopedic doctor should be able to advise accordingly.

Moses Ndiritu’s story – Every day gets harder

Pain Management

Managing the severe pain associated with HME can be very disheartening, and there are all sorts of opinions regarding treatment. Below are several different approaches to pain management, notwithstanding that fact that in distinguishing which pain medicine provides the most effective relief it is important for each HME patient (or parent / guardian in the case of children) to do their own research before any new treatments are commenced. While a proposed treatment may sound beneficial, there are also some potential negative side effects that a HME patient may suffer from. Always be aware of both the pros and cons of any treatment before deciding whether it is the right approach to controlling specific pain, and preferably use the therapy in a controlled environment.

1. Medical Marijuana?

While the MHE Research Foundation does not support the use of Medical Marijuana, HME is one of a defined number of conditions with symptoms or ailments that advocates claim can treated with Medical Marijuana.  Stockbroker and HME patient Irvin Rosenfeld, from Fort Lauderdale, Florida, has been issued with 12 daily government-supplied marijuana cigarettes for more than 30 years. The longest surviving patient to be assigned to the federal medical marijuana, Mr. Rosenfield claims he would not be alive if he hadn’t been issued with marijuana cigarettes for the treatment of his HME condition.

For more on Irvin Rosenfeld (http://irvinrosenfeld.com/), refer to the YouTube video ‘Medical Marijuana – Multiple Exostoses (Irvin Rosenfeld)’ below.

In Canada, Saskatoon high school student Michael Wileniec says high-grade medical marijuana is the only drug that eases his chronic pain,  noting in a January 2015 newspaper interview, he had already “…tried conventional prescription drugs, from Tylenol 3 to morphine, but didn’t like how they clouded his mind“.

For more about Michael Wileniec and his usage of Medical Marijuana to help alleviate HME related pain refer to:

http://www.thestarphoenix.com/health/Student+banned+from+using+medical+marijuana+school/10737686/story.html

2. Traditional Chinese Medicine?

Having lived in China for a number of years I have had the benefit of trying out traditional acupuncture, electroacupuncture, and tuina acupressure, the needle free alternative to acupuncture. These Traditional Chinese Medicine  treatments are effective paint controls, although I found the relief to be short lived, meaning that once treatment concluded the soreness would soon return. For specific HME patient feedback regarding the effectiveness of such Traditional Chinese Medicine practices, including qigong read the “Comments” https://nialljoreilly.com/2012/04/28/hereditary-multiple-exostoses-ireland/#comments section located at the bottom of this post.

Learning to Love Myself and My Scars From Multiple Hereditary Exostoses

3. Omega-3 Krill Oil? 

Having endured an agonising winter of 2013 / 2014, to the point where even a walk of 20 metres could be a harrowing exercise -the degree of tenderness contingent on the prevailing weather-  my introduction to the benefits of Omega-3 Krill Oil, which the Journal of Lipid Research claims is 48 times more potent than fish oil, was simply a business-driven fluke. Yet, while there are no research studies to back me up, I have found exceptional relief (reduced pain, inflammation, functional impairment, stiffness) since the summer of 2014 when I started taking Omega-3 Krill Oil in capsule (500 mg per day) and more recently in syrup format. In fact, of late, since finishing the bottle of Omega-3 Krill Oil (300 ml) syrup in late January (2015), once again I can now feel both bone and joint pain levels starting to give me a hard time.

The Omega-3 Krill Oil capsule and syrup products I used are from CleanMarine (http://www.cleanmarine.ie/), who also produce a Krill Oil syrup for kids.

4. Homeopathy

Advocates of homeopathy for HME contend that surgical excision of exostoses does not remove the cause of HME, as it cannot guarantee further exostoses  from forming. Homeopathists aim to treat the patient (not HME) by strengthening his/her immune system to remove the disease and prevent recurrence.

5. Tablets / Capsules

I am not a fan of tablets, but at home I do keep  Solpadol Caplets handy. Unfortunately, these are codeine-based, so need a prescription for good reason. They have the effect of bring a Level 8 pain down to a more manageable Level 5 or 6.

For severe pain doctors have also prescribed OxyNorm and Tramadol, but these are really heavy pain-killers and  I’d rather deal with the pain in my own way than have to take these for a prolonged period

HME NEWS FROM 2017

“Preclinical study demonstrates promising treatment for rare bone disease

Data supports clinical investigations of palovarotene to treat multiple hereditary exostoses”

La Jolla, Calif., November 20, 2017 – Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) have led a preclinical study demonstrating that the drug palovarotene suppresses the formation of bony tumors (osteochondromas) in models of multiple hereditary exostoses (MHE). The research, published in the Journal of Bone and Mineral Research, is an important step toward an effective pharmacological treatment for MHE, a rare genetic condition that affects about 1 in 50,000 people worldwide.

MHE (also known as multiple osteochondromas, or MO) is an inherited genetic disorder in which multiple benign bone tumors covered with cartilage grow at active areas of bone growth. The condition is caused by mutations in two genes: EXT1 and EXT2. Individuals with these mutations develop painful, debilitating tumors, often repeatedly during their childhood and adolescence. Surgery and pain management are currently the only treatment options for MHE patients.

“Our study shows that palovarotene is a remarkably potent inhibitor of osteochondromas, says Yu Yamaguchi, M.D., Ph.D., professor at SBP. “In our mouse model of MHE, we were able to reduce bone tumors by more than 90 percent, which is a significant improvement over the previous drugs we have tested in the same mouse model.”

“Especially promising is that palovarotene has been tested for toxicity and side effects in humans and has been shown to be well tolerated,” says Yamaguchi. “This means that time line for getting the drug to the clinic for MHE may be shortened.”

Clementia Pharmaceuticals licensed palovarotene from Roche Pharmaceuticals, which previously investigated the compound as a possible treatment for chronic pulmonary disease and evaluated its safety in more than 800 healthy volunteers and patients. Clementia Pharmaceuticals is planning to initiate a Phase 2/3 clinical trial in 2018 for patients with MHE.

“This is first time we are seeing a clear path toward a therapy that will improve the lives of MHE patients and their families,” says Sarah Ziegler, vice-president of the MHE Research Foundation. “The long awaited first clinical trial for a drug to treat MHE is now a reality. This breakthrough comes after years of working with medical professionals and scientists like Dr. Yamaguchi to achieve something we have all been desperately striving for, for many years.”

Source: https://www.mherf.org/

Shania’s HME

Prognosis – The Good News

Through gene mapping studies scientists, as previously noted, have linked HME with mutations in three genes:  EXT1, which maps to Chromosome 8q24.1; EXT2 which maps to Chromosome 11p13;  and EXT3 which maps to the short arm of Chromosome 19 (though its precise location is still unclear). 

Continuing research of the HME genes will likely establish an accurate prevalence for each of the three gene types, thus providing greater insight into the growth of cells, which is really what HME is all about. With such rapid advances in science, particularly in terms of gene mapping, it not inconceivable that such as understanding will sooner rather than later provide the knowledge leading to a tangible treatment for HME.

Recently, Chinese scientists, supported by the Ministry of Science and Technology, have also started conducting extensive research into HME. One such research paper published in 2014 concluded that in China:

“HME starts earlier and becomes more severe and extensive with each successive generation in members of the pedigree analyzed”

[For more about HME in China refer to ‘10. Instances of Hereditary Multiple Exostoses (HME) in China, from 1990 – 2013′  in the research segment at the bottom of this blog.

In addition, ‘11. The link http://www.cancerindex.org/geneweb//X0205.htm‘ in the research segment below provides a detailed overview of the latest HME-related research worldwide.]. 

As it stands, gene mapping can serve as a basis for testing children at risk with HME and the information gleaned from such testing will hopefully lead to the prevention of the development of exostoses and their associated complications. There is good reason for optimism: the day when our doctors are equipped to undertake such testing is near.

Multiple Hereditary Osteochondromatosis (MHO)* – Suzie’s Story

*Multiple Hereditary Osteochondromatosis is the official World Health Organisation term for HME / MHE

Osteochondroma… this is My story

HME and Autism / Asperger Syndrome Linkage?

Heparan Sulphate and MHE – Dr. Yu Yamaguchi. Many parents of children with MHE / HME / MHO frequently observe autism and Asperger Syndrome like social issues in their children

HME and Animals?

St. Bernard dog http://onlinelibrary.wiley.com/doi/10.1111/vru.12066/abstract Domestic pig  http://vdi.sagepub.com/content/early/2013/06/27/1040638713495545.full

Bone Lengthening Surgery?

“….“The bumps themselves are not so much a problem, what tends to cause the issue in children or even in adults is if [the bumps] are causing deformity,” explains Dr. Carmen Brauer, an orthopediatric surgeon with the Alberta Children’s Hospital. “Bone lengthening in the upper extremity is fairly rare compared to the lower extremity, and here at the Alberta Children’s Hospital we hadn’t done any lengthening of the upper extremity,” Dr. Brauer says. A team was assembled to perform the first procedure on Dunbar last June. His bone was cut and a device was implanted to apply tension over time to help the bone to grow. “We slowly distract and the bone then heals under the tension we’re applying. By doing that we can lengthen the bone up to a millimeter a day,” Dr. Brauer explains…….” Source / read more and view the Video: http://globalnews.ca/news/907083/bone-lengthening-surgery-saves-calgary-boy-from-disability/

Dorsal Foot Exostosis

Dorsal foot exostosis is a bony growth on the dorsum (top) of the foot.  It can occur where the first metatarsal joint meets the big toe, causing the toe to lose its ability to bend. This is also known as Hallux rigidus (inability to move the joint) or Hallux limitus (limited movement of the big toe). Acute or chronic pain on the top of the foot happens in the morning and as the day progresses, more so the longer a person is standing. Metatarsal Cuneiform Exostoses crop up in the midfoot area, where the first metatarsal shaft meets the cuneiform, while a forefoot version of Haglund’s Deformity is where the throat line of the shoe meeting the foot causes pressure and rubbing which results in the fleshy area behind the toes..

Is that a Bunion or an Exostosis protruding from your foot?

– “A large exostosis was the source of a bunion deformity in a 60-year-old woman. Its unusual clinical and radiographic features were suggestive of a bizarre parosteal osteochondromatous proliferation. However, histologic features were most consistent with a benign osteocartilaginous exostosis…..” Source / read more: http://www.ncbi.nlm.nih.gov/pubmed/11482512

Orthopaedic / Neurological  Consultant / Surgeon HME Knowhow in Ireland

Unfortunately, GPs / HSE in Ireland have little or no knowledge of HME. Best to have a GP refer you to a consultant orthopedic surgeon specialising in the specific area that causes most discomfort. No one consultant will cover all areas affected by HME. I ended up doing the research myself and then asking the GP to contact the consultants I deemed applicable to my needs.

Below is what I would consider to be the best neuro / orthopaedic surgeon team in Ireland: Perfectionists, professional, friendly beside manner. They really listen.

These guys are very well grounded, I cannot rate them highly enough, they know the score and have the know-how when it comes to dealing with HME. Interestingly, they mentioned they tended to deal more with cases of single exostosis, and that multiple exostoses was still quite rare in Ireland.

Typically, the first consultant you engage with should take the lead in calling in other neuro / orthopaedic specialists either to verify a particular prognosis or to advise on specific areas beyond his area of  expertise.

• Mr. Hannan Mullett (Shoulder), Blackrock Clinic, Beaumont Hospital, Sports Surgery Clinic, Cappagh National Orthopedic Hospital
• Mr. Philip P. Grieve (Elbow, Hand, and Wrist), Blackrock  Clinic
• Mr. Alan Liang (Foot and Ankle), Blackrock Clinic, Beacon Hospital
• Mr. Fintan Doyle (Hip and knee), Blackrock Clinic
• Mr. Eoin Fenton   (Neurosurgery, Spine), Blackrock Clinic
• Dr. Sean Connelly (Neurophysiology), Blackrock  Clinic

Tip: Make sure you have health insurance. MRIs at Blackrock Clinic should be fully covered by VHI, but not CTs. CTs are fully covered by VHI at the Affidea clinics. For x-rays public hospitals have walk in services, which cost about €50.00, rather than €100.00 + in the private hospitals

Useful Support Resources for HMEers and their families

Five Facebook Support Groups

MHE & HME & MO Support Group

Chondrosarcoma Support Group Community

MHE Awareness Group

HME – The New Generation

HME

USA / International

• The MHE Coalition http://www.mhecoalition.org/ Facebook page appears to be more active: https://www.facebook.com/pages/MHE-Coalition/112229608822423 –Excellent particularly with respect to ongoing research and contributions from medical experts.
• MHE and Me http://www.mheandme.com –A support group for children with MHE / HME, which also publishes a useful handbook [A member of the MHE Coalition].

United Kingdom / International

• Hereditary Multiple Exostoses (HME) Support Group http://www.hmesg.org.uk/ Facebook Page: https://www.facebook.com/pages/HME-Support-Group/129536527204525

– This support group has a very instructive web site and hosts an international notice board.

Netherlands (Dutch and English)

• Hereditaire Multiple Exostosen Lotgenotencontactgroep / HME-MO Vereniging Nederland http://www.hme-mo.nl/

– The Dutch HME-MO Association website provides an all encompassing platform which features an English section.

Australia (English)

• MHE 4 Aussies  https://www.facebook.com/groups/187166979593/

– Hereditary Multiple Exostoses (HME) support in Australia.

New Zealand (English)

• HME / MHE 4 NZ Multiple Hereditary Exostoses Group  https://www.facebook.com/NZMHE/

– Hereditary Multiple Exostoses (HME) support group in New Zealand. 

France / Belgium (French)

• L’AMem – Association de la Maladie des Exostoses Multiples http://www.amem.fr

– This support group offers support for almost 400 families in France (and some also from Belgium)

Spain (Spanish)

• AEOMC – Asociación Española de Osteocondromas Múltiples Congénitos https://www.facebook.com/groups/28347088874/

– This support blog offers support for families in Spain.

Germany (German)

• Multiple Kartilaginare Exostosen http://www.exostosen.de/cms/front_content.php

– This support group offers a German translation of The MHE and Me Handbook

Norway (Norwegian)

• Norsk MO-forening http://norskmheforening.no/

– This support group offers support for families in Norway

Ireland

• Hereditary Multiple Exostoses (HME) and Me HME Support in Ireland

– Despite evidence of HME occurring in 4 ancient Irish skeletal remains (“Ballyhanna Man“) of only 16 ancient skeletal remains worldwide diagnosed with HME bone growth disorder, Ireland doesn’t have an official HME information support group, hence this blog.

HME Research

1. MHE Research Foundation http://www.mheresearchfoundation.org/ –  Dedicated to researching for the cure to Hereditary Multiple Exostoses / Multiple Osteochondroma.

1. National Center for Biotechnology Information (NCBI) http://www.ncbi.nlm.nih.gov/sites/ga?disorder=multiple%20hereditary%20exostoses – Up to date website with detailed information on Hereditary Multiple Exostoses (HME). Includes: * Links to introductory material about Multiple Hereditary Exostoses and genetics. * NCBI Book sections and chapters about Multiple Hereditary Exostoses and genetics. * Recent scientific articles about Multiple Hereditary Exostoses. * Links to resources for screening, genetic testing, and directories of specialists.

1. PAPER – Cervical spinal cord compression in hereditary multiple exostoses Abstract– Spinal cord compression is an extremely serious complication of hereditary multiple exostoses (HME). A case of HME with compression of the cervical spinal cord is reported. Complete recovery following surgery was achieved. A review of the relevant literature revealed 51 previous cases of HME with cord/cauda equina compression. Most patients were under 30 years of age with more men affected than women. The family history was positive in 60%. The cervical and thoracic areas were predominantly affected, with the symptoms usually developing slowly. Recovery following surgery is to be expected in the majority of cases. In patients with HME and suffering from neurological symptoms, the possibility of spinal cord compression should be considered. Prompt diagnosis and surgical excision provide the best prognosis. Source / read more: http://www.ncbi.nlm.nih.gov/pubmed/9006779

1. ONGOING RESEARCH – Call for participants – Gene Mutations and Orthopaedic Symptoms Correlation of Multiple Hereditary Exostoses: Multicentre Project.

   Source / read more http://clinicaltrials.gov/show/NCT00474331 

1. PAPER (Chinese)- Ultrastructural features of hereditary multiple osteochondroma cartilage cap in children Abstract –目的观察儿童遗传性多发性骨软骨瘤（hereditary multiple exostoses, HME）软骨帽的超微结构，为儿童HME超微病理诊断提供可靠依据。方法实验组：切除18例HME患儿肋骨瘤体分离软骨帽；对照组：15例胸廓发育畸形患儿手术矫正切除的肋软骨；分别取其纵、横切面应用扫描电镜和透射电镜观察。结果对照组：冷冻断裂的软骨组织内见少量软骨细胞位于软骨陷窝内，软骨组织表面可见大量散乱、稀疏的胶原纤维；软骨细胞数量不多，细胞表面有少量短小的微绒毛，细胞核形状不规则，细胞质内可见到粗面内质网呈条索样分散在细胞质内，线粒体较小，糖原颗粒呈簇状分布。实验组：冷冻断裂的软骨组织内见大量不规则的软骨陷窝，每个软骨陷窝内均含有软骨细胞，细胞表面有丰富的细胞突起；软骨组织内见大量瘤样细胞增生，聚集分布，细胞核较大，细胞质内可见圆形或椭圆形的线粒体及扩张的粗面内质网；瘤细胞间可见毛细血管，其附近可见明显增多的软骨细胞，软骨细胞体积较对照组增大。结论儿童HME软骨帽的超微结构改变（细胞形态及细胞内部细胞器），不同于正常软骨细胞，可能与儿童HME的遗传、发病、发展、转归因素密切相关。 Source / read more: http://www.cjcep.com/oa/darticle.aspx?type=view&id=201302014
2. PAPER – Multiple osteochondromas in the archaeological record: a global review Abstract

…The paper undertakes the first synthesis study of the 16 known cases of the condition that have been identified in the international palaeopathological record. It also includes information derived from two newly discovered cases of the disease in two adult male individuals recovered from the Medieval cemetery at Ballyhanna, Co. Donegal, Ireland. Source / read more: http://www.qub.ac.uk/sites/Ballyhanna/FileStore/Filetoupload,216459,en.pdf

7.  PAPER – Hereditary Multiple Exostoses: A Current Understanding of Clinical and Genetic Advances…Recent advances in understanding the molecular and genetic basis of this condition not only offer hope for patients and families with HME, but also offer clues to the underlying basis for the formation of the human musculoskeletal system… Source / read more: http://upoj.org/site/files/v14/v14_09.pdf

8. INFORMATION: Preimplantation genetic screening (PGS)

“In medicine and (clinical) genetics preimplantation genetic diagnosis (PGD or PIGD) (also known as embryo screening) refers to procedures that are performed on embryos prior to implantation, sometimes even on oocytes prior to fertilization. PGD is considered another way to prenatal diagnosis. Its main advantage is that it avoids selective pregnancy termination as the method makes it highly likely that the baby will be free of the disease under consideration. PGD thus is an adjunct to assisted reproductive technology, and requires in vitro fertilization (IVF) [Note: IVF costs around €4,000, with fertility drugs, if required, costing up to €3,000] to obtain oocytes or embryos for evaluation. 

PGD is also now being performed in a disease called Hereditary multiple exostoses (MHE / MO / HME).. 

The term preimplantation genetic screening (PGS) is used to denote procedures that do not look for a specific disease but use PGD techniques to identify embryos at risk. PGD is a poorly chosen phrase because, in medicine, to “diagnose” means to identify an illness or determine its cause. An oocyte or early-stage embryo has no symptoms of disease. They are not ill. Rather, they may have a genetic condition that could lead to disease. To “screen” means to test for anatomical, physiological, or genetic conditions in the absence of symptoms of disease. So both PGD and PGS should be referred to as types of embryo screening….” Source / read more: http://library.everyonehealthy.com/library/furthertest/In%20Vitro%20Fertilization%20With%20Preimplantation%20Genetic%20Diagnosis

9. NEW RESEARCH: How gene mutations lead to the abnormal bone growth that is Hereditary Multiple Exostoses (MHE)?

In humans, MHE is caused by a mutation in one of two genes, Ext1 or Ext2. Together, these genes encode an enzyme necessary to produce heparan sulfate—a long sugar chain that facilitates cell signals that direct bone cell growth and proliferation. But when these genes were inactivated in mice just as they are in human MHE patients, the mice failed to develop the symptoms of MHE. This had scientists scratching their heads.

Enter Dr. Yamaguchi and his colleagues, who took a different approach. Instead of knocking out the Ext1 gene in the whole mouse, they targeted the gene only in bone cells. Moreover, they deleted the gene in only a small fraction of these cells. Surprisingly, this minimalistic approach led to a mouse with all the physical manifestations of MHE, such as bony protrusions, short stature and other skeletal deformities.

The new mouse model answered some long-standing questions about MHE. Scientists had gone back and forth on whether the abnormal growths observed in MHE are true tumors or just malformations of the bone. In this study, the protrusions were made up of two cell types. A minority were mutant cells lacking Ext1, but, amazingly, most were normal bone cells. True tumors, in the strictest sense, arise from the proliferation of mutant cells only. Hence, MHE bone protrusions must result from a different – though still very serious – type of growth.

“I have been waiting 13 years for this breakthrough,” said Sarah Ziegler, vice president of The MHE Research Foundation, which has provided seed funding for Dr. Yamaguchi’s research. “My son had more than a 100 of these tumors and has gone through 15 surgeries. When your child has such a debilitating condition, and you know there’s nothing you can do, it’s petrifying. Now we have hope.”

While this study takes MHE research a giant step forward, more questions remain. For one, it is still unknown how a few mutant bone cells can convince normal cells to divide and proliferate abnormally. Researchers hope that this MHE model will help solve that mystery, as well as provide leads for new treatments.

“This new mouse system also provides a platform for screening potential drugs that inhibit bone growths in MHE,” Dr. Yamaguchi explained. “We are currently developing chemical inhibitors to block their formation.”

Source / read more: http://phys.org/news194606781.html

10. Instances of Hereditary Multiple Exostoses (HME) in China, from 1990 – 2013

“...Hereditary multiple exostoses (HME) are an autosomal dominant skeletal disease with wide variations in clinical manifestations among different ethnic groups. This study investigated the epidemiology, clinical presentations, pathogenetic features and treatment strategies of HME in mainland China. We searched and reviewed the related cases published since 1990 by searching electronic databases, namely SinoMed database, Wanfang database, CNKI, Web of Science and PubMed as well as Google search engines. A total of 1051 cases of HME (male-to-female ratio 1.5:1) were investigated and the diagnosis was made in 83% before the age of 10 years. Approximately 96% patients had a family history. Long bones, ribs, scapula and pelvis were the frequently affected sites. Most patients were asymptomatic with multiple palpable masses. Common complications included angular deformities, impingement on neighbouring tissues and impaired articular function. Chondrosarcomas transformation occurred in 2% Chinese cases. Among the cases examined, about 18% had mutations in EXT1 and 28% in EXT2. Frameshift, nonsense and missense mutations represented the majority of HME-causing mutations. Diagnosis of HME was made based on the clinical presentations and radiological documentations. Most patients needed no treatment. Surgical treatment was often directed to remove symptomatic exostoses, particularly those of suspected malignancy degeneration, and correction of skeletal deformities. This study shows some variance from current literature regarding other ethnic populations and may provide valuable baseline assessment of the natural history of HME in mainland China.”

– Source: Guo XL, Deng Y, Liu HG, Clinical characteristics of hereditary multiple exostoses: a retrospective study of mainland chinese cases in recent 23 years. J Huazhong Univ Sci Technolog Med Sci. 2014; 34(1):42-50 – See more at: http://www.cancerindex.org/geneweb//X0205.htm

11. The following links http://www.cancerindex.org/geneweb//X0205.htm provides a detailed overview of ongoing HME-related research worldwide. A lot of research is now being conducted on mainland China with conclusions (as per the attached) highlighting that:

– “HME starts earlier and becomes more severe and extensive with each successive generation in members of the pedigree analyzed. A splicing mutation, IVS5+1G>A, of EXT1, first identified in Chinese population, may be responsible for HME in the studied pedigree. EXT1 and EXT2 mutation rates may be different between the Chinese and Western populations – See more at: http://www.cancerindex.org/geneweb//X0205.htm#sthash.JRl5abuL.dpuf“

12.  Hereditary Multiple Exostoses: New Insights into Pathogenesis, Clinical Complications, and Potential Treatments (June 2017)

“Hereditary multiple exostoses (HME) is a complex musculoskeletal pediatric disorder characterized by osteochondromas that form next to the growth plates of many skeletal elements, including long bones, ribs, and vertebrae. Due to its intricacies and unresolved issues, HME continues to pose major challenges to both clinicians and biomedical researchers. The purpose of this review is to describe and analyze recent advances in this field and point to possible targets and strategies for future biologically based therapeutic intervention.

RECENT FINDINGS:

Most HME cases are linked to loss-of-function mutations in EXT1 or EXT2 that encode glycosyltransferases responsible for heparan sulfate (HS) synthesis, leading to HS deficiency. Recent genomic inquiries have extended those findings but have yet to provide a definitive genotype-phenotype correlation. Clinical studies emphasize that in addition to the well-known skeletal problems caused by osteochondromas, HME patients can experience, and suffer from, other symptoms and health complications such as chronic pain and nerve impingement. Laboratory work has produced novel insights into alterations in cellular and molecular mechanisms instigated by HS deficiency and subtending onset and growth of osteochondroma and how such changes could be targeted toward therapeutic ends. HME is a rare and orphan disease and, as such, is being studied only by a handful of clinical and basic investigators. Despite this limitation, significant advances have been made in the last few years, and the future bodes well for deciphering more thoroughly its pathogenesis and, in turn, identifying the most effective treatment for osteochondroma prevention.”

Source / Author: https://www.ncbi.nlm.nih.gov/pubmed/28466453 2017 Translational Research Program in Pediatric Orthopaedics, Abramson Research Center, 902D, Division of Orthopaedic Surgery, Department of Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA. pacificim@email.chop.edu.

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2019

2019