CONFERENCE REPORT
Summary Of The 2nd International Symposium On Arthrogryposis, St. Petersburg, Russia, September 17-19, 2014 Judith G. Hall,1* Alga Ogranovich,2 Ava Ponte´n,3 and Harold J. P. van Bosse4 1
Departments of Medical Genetics and Pediatrics, University of British Columbia and BC Children’s Hospital Vancouver, British Columbia, Canada 2
Arthrogrpyosos Clinic, Turner Scientific and Research Institute for Children’s Orthopedics, Saint-Petersburg, Russia Department of Pediatric Orthopedic Surgery, Karolinska University Hospital, Stockholm, Sweden
3 4
Department of Orthopedic Surgery, Shriners Hospital for Children, Philadephia, Pennsylvania
Manuscript Received: 20 November 2014; Manuscript Accepted: 7 December 2014
Enormous progress has been made in understanding the etiology and therapies for arthrogryposis (multiple congenital contractures). A 2nd International Symposium on Arthrogryposis was sponsored by the Turner Institute in St. Petersburg, Russia. Olga Agranovich, Head of the Arthrogryposis Department of the Turner Institute, organized this special meeting. Care providers from multiple disciplines from all over the world representing 18 nations attended. Participants included: Pediatric orthopedic specialists, rehabilitation physicians, occupational therapists, physical therapists, medical geneticists, neurologists, craniofacial physicians, psychologists, developmental biologists, as well as representatives from parent support groups. The 1st symposium established the need for a collaborative and interdisciplinary approach to the treatment of arthrogryposis, engagement of parent support organizations, and the aim for more research. The Second Symposium highlighted the continuing need for more research on various therapies, identification of different types of arthrogryposis, standardized descriptions of severity, development of new orthotics, improved prenatal diagnosis, and studying adult outcome. Major progress has been made on both upper and lower limb treatments. Ó 2015 Wiley Periodicals, Inc.
Key words: arthrogryposis; multiple congenital contractures; international symposium; treatment; therapy; classification; support group; adults; children; newborns; Ponseti method; prenatal diagnosis; genetic basis; natural history; epidemiology
INTRODUCTION Enormous progress has been made in understanding the etiology and therapies for arthrogryposis (multiple congenital contractures). The symposium was sponsored by the Turner Institute in St. Petersburg, Russia partly because of the enormous progress that has been made through the multi-disciplinary approach taken by that institution. Dr. Ruth Lester, who organized the 1st International Symposium on Arthrogryposis in Birmingham, UK, and
Ó 2015 Wiley Periodicals, Inc.
How to Cite this Article: Hall JG, Ogranovich A, Ponte´n A, van Bosse HJP. 2015. Summary of the 2nd international symposium on arthrogryposis, St. Petersburg, Russia, September 17-19, 2014. Am J Med Genet Part A 9999A:1–3.
Olga Agranovich, Head of the Arthrogryposis Department of the Turner Institute, organized this very special meeting. Care providers from multiple disciplines from all over the world attended. Eighteen nations were involved. Attendees included: pediatric orthopedic specialists, rehabilitation physicians, occupational therapists, physical therapists, medical geneticists, neurologists, craniofacial physicians, psychologists, developmental biologists, as well as representatives from parent support groups. The 1st International Symposium established the need for a collaborative and interdisciplinary approach to the treatment of arthrogryposis, engagement of parent support organizations, and the need for more research. Those issues were highlighted again, as well as an emphasis on uniqueness of each affected individual’s situation, the need for knowledge about outcomes in adults with arthrogryposis, and a re-emphasis on a definition of arthrogryposis as including multiple congenital contractures in two or more body areas (even though familial types of arthrogryposis may have great Conflict of interest: None. Correspondence to: Judith G. Hall, O.C., M.D., FRSC, FCAHS, Department of Pediatrics, British Columbia’s Children’s Hospital, 4500 Oak Street, Room C234, Vancouver, BC, Canada, V6H 3N1. E-mail: [email protected] Article first published online in Wiley Online Library (wileyonlinelibrary.com): 00 Month 2015 DOI 10.1002/ajmg.a.36938
1
2 variability within a family). In addition, there was a recognition that although Amyoplasia is the most common type of arthrogryposis, the hundreds of other types of arthrogryposis often require similar therapies, but many have different natural histories, need to be distinguished and identified, and need to have any specific therapies that are needed determined.
Highlights of the Symposium and Take Home Messages Included: 1. There is a great need for more research with controls or blinded studies which engage specific subtypes of affected individuals. The need for multicenter trials and collaborations was emphasized because of the relative rarity of most types of arthrogryposis. 2. Over 150 genes have been recognized to be related to different types of arthrogryposis. Developmental and molecular genetics are providing insight into the pathways of specific genes and may provide insight into therapies in the future. The unusual patient or responses are important to report since they may provide new insights or particular precautions. 3. It was agreed that consensus needs to be developed by those providing therapy concerning the classification(s) of severity in order to be able to properly assess short term and long term outcomes and compare studies. 4. There was a great deal of discussion about how to manage affected individuals in the newborn period and during the first six months. Studies are needed as to whether early mobilization in arms and legs allow for identification and preserve functional muscle where as immediate casting or surgery may lead to muscle atrophy. However, there was general agreement that Ponseti type casting should begin by 1–2 months of age for clubfeet and knee dislocations should be casted. 5. The issue of how much muscle is present at birth and what happens to muscle under various therapies needs greater exploration. Early imaging of muscle by ultrasound or MRI would seem to be important as a baseline for determination of best therapy and long term outcomes (for instance as to whether or not walking can be anticipated). 6. Dramatic improvement in the upper limbs of individuals with amyoplasia utilizing vigorous physical therapy and muscle transfers was reported from several centres. Studies need to be undertaken to identify which patients and which procedures will be most effective in various types of arthrogryposis. 7. Concerning orthotics for adults with arthrogryposis, many need them for stabilization during walk, and a carbon spring built into an ankle-foot-orthosis may function as muscle when muscles are absent or very weak. 8. The new use of the “8-plate” provides temporary hemiephysiodesis with a small plate and screws. It has revolutionized the
AMERICAN JOURNAL OF MEDICAL GENETICS PART A treatment of malaligned knees in the older child, since it is less traumatic than osteotomies and spares muscle tissue. 9. In individuals with arthrogryposis and scoliosis, growing rods have been very useful. 10. Some discussions occurred about the depositions of extra connective tissue around affected joints and the thickening of the joint capsule in affected individuals. This extra connective tissue seems most responsive to physical therapy during the first few months—whether this is related to early infant physiology or remaining maternal hormones is not clear. However, stretching with the Ilizarov apparatus and early utilization of the Ponseti successive casting both seem to have important non-surgical affects on the extra connective tissue suggesting they both lead to the release of cytokines that could be identified and utilized in the future in therapy for arthrogryposis. 11. To date, very little data exist on adult outcomes. It is clear that the therapies utilized 20–30 years ago are now associated in older affected individuals with degenerative arthritis and pain in affected joints in most adults. In addition, immobilization of adults with arthrogryposis (even for short periods of time) seems to lead to disproportionate weakness and muscle atrophy. Becoming overweight is also a problem for adults with arthrogryposis (as it can be for children). Thus, adults with arthrogryposis should keep as active as possible. Most community ambulators continue to require bracing for support. 12. Improved prenatal diagnosis should be attainable since most types of arthrogryposis already have developed joint contractures during the second trimester which can be identified using real time ultrasound prenatally. Unfortunately, leg and arm movement (much less the movement of feet and hands) is not examined routinely by prenatal ultrasoundography and the available data suggests that less than 25% of cases of Amyoplasia are diagnosed prenatally. The failure to make a diagnosis prenatally prevents parents and clinicians the opportunity for appropriate decision making, the possibility of in utero therapy (increasing movement in utero), or early delivery at a time when lungs are mature and the contractures may not be so severe. 13. Epidemiologic studies and more specific ICD codes are needed for all types of multiple congenital contractures (including among terminations and stillborns). The occurrence of arthrogryposis appears to be in the range of 1 in 3,000–4,000 births. However, ICD codes do not, at this time, allow for surveillance and monitoring of specific subtypes. 14. Limited jaw opening and malignant hyperthermia are known to complicate anaesthesia in arthrogryposis, and since multiple surgeries are often needed, better understanding of these complications or any other increased risks is desirable.
HALL ET AL. 15. With advances in stem cell research, it seems possible that stem cell therapy, both involving muscle and nerve, cells may eventually play a role in the treatment of arthrogryposis. 16. There was general consensus that guidelines regarding various therapies, for sub-classification of severity, and for the order of various therapies need to be developed. Perhaps before the next
3 meeting in 2018, working groups can be undertaken to define and develop these complex issues.
ACKNOWLEDGMENTS Particular thanks to Dr. Ruth Lester, Dr. Olga Agranovich, and the Turner Institute for organizing this outstanding scientific meeting.
Summary Of The 2nd International Symposium On Arthrogryposis, St. Petersburg, Russia, September 17-19, 2014 Judith G. Hall,1* Alga Ogranovich,2 Ava Ponte´n,3 and Harold J. P. van Bosse4 1
Departments of Medical Genetics and Pediatrics, University of British Columbia and BC Children’s Hospital Vancouver, British Columbia, Canada 2
Arthrogrpyosos Clinic, Turner Scientific and Research Institute for Children’s Orthopedics, Saint-Petersburg, Russia Department of Pediatric Orthopedic Surgery, Karolinska University Hospital, Stockholm, Sweden
3 4
Department of Orthopedic Surgery, Shriners Hospital for Children, Philadephia, Pennsylvania
Manuscript Received: 20 November 2014; Manuscript Accepted: 7 December 2014
Enormous progress has been made in understanding the etiology and therapies for arthrogryposis (multiple congenital contractures). A 2nd International Symposium on Arthrogryposis was sponsored by the Turner Institute in St. Petersburg, Russia. Olga Agranovich, Head of the Arthrogryposis Department of the Turner Institute, organized this special meeting. Care providers from multiple disciplines from all over the world representing 18 nations attended. Participants included: Pediatric orthopedic specialists, rehabilitation physicians, occupational therapists, physical therapists, medical geneticists, neurologists, craniofacial physicians, psychologists, developmental biologists, as well as representatives from parent support groups. The 1st symposium established the need for a collaborative and interdisciplinary approach to the treatment of arthrogryposis, engagement of parent support organizations, and the aim for more research. The Second Symposium highlighted the continuing need for more research on various therapies, identification of different types of arthrogryposis, standardized descriptions of severity, development of new orthotics, improved prenatal diagnosis, and studying adult outcome. Major progress has been made on both upper and lower limb treatments. Ó 2015 Wiley Periodicals, Inc.
Key words: arthrogryposis; multiple congenital contractures; international symposium; treatment; therapy; classification; support group; adults; children; newborns; Ponseti method; prenatal diagnosis; genetic basis; natural history; epidemiology
INTRODUCTION Enormous progress has been made in understanding the etiology and therapies for arthrogryposis (multiple congenital contractures). The symposium was sponsored by the Turner Institute in St. Petersburg, Russia partly because of the enormous progress that has been made through the multi-disciplinary approach taken by that institution. Dr. Ruth Lester, who organized the 1st International Symposium on Arthrogryposis in Birmingham, UK, and
Ó 2015 Wiley Periodicals, Inc.
How to Cite this Article: Hall JG, Ogranovich A, Ponte´n A, van Bosse HJP. 2015. Summary of the 2nd international symposium on arthrogryposis, St. Petersburg, Russia, September 17-19, 2014. Am J Med Genet Part A 9999A:1–3.
Olga Agranovich, Head of the Arthrogryposis Department of the Turner Institute, organized this very special meeting. Care providers from multiple disciplines from all over the world attended. Eighteen nations were involved. Attendees included: pediatric orthopedic specialists, rehabilitation physicians, occupational therapists, physical therapists, medical geneticists, neurologists, craniofacial physicians, psychologists, developmental biologists, as well as representatives from parent support groups. The 1st International Symposium established the need for a collaborative and interdisciplinary approach to the treatment of arthrogryposis, engagement of parent support organizations, and the need for more research. Those issues were highlighted again, as well as an emphasis on uniqueness of each affected individual’s situation, the need for knowledge about outcomes in adults with arthrogryposis, and a re-emphasis on a definition of arthrogryposis as including multiple congenital contractures in two or more body areas (even though familial types of arthrogryposis may have great Conflict of interest: None. Correspondence to: Judith G. Hall, O.C., M.D., FRSC, FCAHS, Department of Pediatrics, British Columbia’s Children’s Hospital, 4500 Oak Street, Room C234, Vancouver, BC, Canada, V6H 3N1. E-mail: [email protected] Article first published online in Wiley Online Library (wileyonlinelibrary.com): 00 Month 2015 DOI 10.1002/ajmg.a.36938
1
2 variability within a family). In addition, there was a recognition that although Amyoplasia is the most common type of arthrogryposis, the hundreds of other types of arthrogryposis often require similar therapies, but many have different natural histories, need to be distinguished and identified, and need to have any specific therapies that are needed determined.
Highlights of the Symposium and Take Home Messages Included: 1. There is a great need for more research with controls or blinded studies which engage specific subtypes of affected individuals. The need for multicenter trials and collaborations was emphasized because of the relative rarity of most types of arthrogryposis. 2. Over 150 genes have been recognized to be related to different types of arthrogryposis. Developmental and molecular genetics are providing insight into the pathways of specific genes and may provide insight into therapies in the future. The unusual patient or responses are important to report since they may provide new insights or particular precautions. 3. It was agreed that consensus needs to be developed by those providing therapy concerning the classification(s) of severity in order to be able to properly assess short term and long term outcomes and compare studies. 4. There was a great deal of discussion about how to manage affected individuals in the newborn period and during the first six months. Studies are needed as to whether early mobilization in arms and legs allow for identification and preserve functional muscle where as immediate casting or surgery may lead to muscle atrophy. However, there was general agreement that Ponseti type casting should begin by 1–2 months of age for clubfeet and knee dislocations should be casted. 5. The issue of how much muscle is present at birth and what happens to muscle under various therapies needs greater exploration. Early imaging of muscle by ultrasound or MRI would seem to be important as a baseline for determination of best therapy and long term outcomes (for instance as to whether or not walking can be anticipated). 6. Dramatic improvement in the upper limbs of individuals with amyoplasia utilizing vigorous physical therapy and muscle transfers was reported from several centres. Studies need to be undertaken to identify which patients and which procedures will be most effective in various types of arthrogryposis. 7. Concerning orthotics for adults with arthrogryposis, many need them for stabilization during walk, and a carbon spring built into an ankle-foot-orthosis may function as muscle when muscles are absent or very weak. 8. The new use of the “8-plate” provides temporary hemiephysiodesis with a small plate and screws. It has revolutionized the
AMERICAN JOURNAL OF MEDICAL GENETICS PART A treatment of malaligned knees in the older child, since it is less traumatic than osteotomies and spares muscle tissue. 9. In individuals with arthrogryposis and scoliosis, growing rods have been very useful. 10. Some discussions occurred about the depositions of extra connective tissue around affected joints and the thickening of the joint capsule in affected individuals. This extra connective tissue seems most responsive to physical therapy during the first few months—whether this is related to early infant physiology or remaining maternal hormones is not clear. However, stretching with the Ilizarov apparatus and early utilization of the Ponseti successive casting both seem to have important non-surgical affects on the extra connective tissue suggesting they both lead to the release of cytokines that could be identified and utilized in the future in therapy for arthrogryposis. 11. To date, very little data exist on adult outcomes. It is clear that the therapies utilized 20–30 years ago are now associated in older affected individuals with degenerative arthritis and pain in affected joints in most adults. In addition, immobilization of adults with arthrogryposis (even for short periods of time) seems to lead to disproportionate weakness and muscle atrophy. Becoming overweight is also a problem for adults with arthrogryposis (as it can be for children). Thus, adults with arthrogryposis should keep as active as possible. Most community ambulators continue to require bracing for support. 12. Improved prenatal diagnosis should be attainable since most types of arthrogryposis already have developed joint contractures during the second trimester which can be identified using real time ultrasound prenatally. Unfortunately, leg and arm movement (much less the movement of feet and hands) is not examined routinely by prenatal ultrasoundography and the available data suggests that less than 25% of cases of Amyoplasia are diagnosed prenatally. The failure to make a diagnosis prenatally prevents parents and clinicians the opportunity for appropriate decision making, the possibility of in utero therapy (increasing movement in utero), or early delivery at a time when lungs are mature and the contractures may not be so severe. 13. Epidemiologic studies and more specific ICD codes are needed for all types of multiple congenital contractures (including among terminations and stillborns). The occurrence of arthrogryposis appears to be in the range of 1 in 3,000–4,000 births. However, ICD codes do not, at this time, allow for surveillance and monitoring of specific subtypes. 14. Limited jaw opening and malignant hyperthermia are known to complicate anaesthesia in arthrogryposis, and since multiple surgeries are often needed, better understanding of these complications or any other increased risks is desirable.
HALL ET AL. 15. With advances in stem cell research, it seems possible that stem cell therapy, both involving muscle and nerve, cells may eventually play a role in the treatment of arthrogryposis. 16. There was general consensus that guidelines regarding various therapies, for sub-classification of severity, and for the order of various therapies need to be developed. Perhaps before the next
3 meeting in 2018, working groups can be undertaken to define and develop these complex issues.
ACKNOWLEDGMENTS Particular thanks to Dr. Ruth Lester, Dr. Olga Agranovich, and the Turner Institute for organizing this outstanding scientific meeting.
