- Email: [email protected]
Osteogenesis imperfecta type VIII: A case report
Journal of Neonatal Nursing (2012) 18, 217e220
www.elsevier.com/jneo
Osteogenesis imperfecta type VIII: A case report Stacy Hines-Dowell b, Shirleatha Lee a,*, Susie Baskin b, Ana Janecek b, Leslie Rhodes b, Flotyl Gresham b a
The University of Memphis, Newport Hall 210, 610 Goodman, Memphis, TN 38152, USA University of TN Le Bonheur Pediatric Specialist (ULPS), Le Bonheur Children’s Hospital, Memphis, TN, USA
b
Available online 3 December 2011
KEYWORDS Osteogenesis; Imperfecta; Bone; Genetic
Abstract Osteogenesis imperfecta is a genetic bone disorder that requires a multi-disciplinary healthcare team to achieve optimal patient outcomes. It is most recognized by excessive brittleness of the bones, and has several classification types, with varying levels of severity. In 2007, type VIII was added to the classification system as a severely deforming and lethal autosomal recessive gene associated with mutations of CRTAP and LEPRE1 genes. The purpose of this case report is to describe a rare case of osteogenesis imperfecta type VIII in the neonate and the multi-disciplinary approach required to manage the patient’s care; that includes a variety of nursing specialties. ª 2011 Neonatal Nurses Association. Published by Elsevier Ltd. All rights reserved.
Introduction This case report describes the multi-disciplinary care of a neonatal patient diagnosed with osteogenesis imperfecta type VIII. Osteogenesis imperfecta is a rare group of heritable metabolic bone disorders characterized by varying degrees of skeletal fragility (Kocher and Shapiro, 1998). It is the most common genetic disorder of the bones with wide-ranging clinical presentations (Monti et al., 2010). Because of the various clinical
* Corresponding author. Tel.: þ1 901 678 2036. E-mail address: [email protected] (S. Lee).
presentations of osteogenesis imperfecta, there are several systems of classification. The original classification system was proposed by Sillence and colleagues in 1979 and has continued to expand over the years with the discovery of new information about the disorder (Arundel and Bishop, 2010). In 2007, the identification of specific clinical features and differences in genetic mutations among some patients with osteogenesis imperfecta led to a proposal to add type VIII to the osteogenesis imperfecta classification system (Dijk et al., 2010). This proposal by Cabral and colleagues was made based on the identification of mutations due to LEPRE1 in patients with osteogenesis imperfecta (Cabral et al., 2007).
1355-1841/$ - see front matter ª 2011 Neonatal Nurses Association. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jnn.2011.11.009
218 Shapiro and Sponseller (2009) classify osteogenesis imperfecta Type VIII as a severe and lethal autosomal recessive gene associated with mutations of CRTAP and LEPRE1 genes that primarily affects South African blacks. The clinical presentation of patients with osteogenesis imperfecta type VIII is one of severe growth and mineralization deficiencies and accounts for fewer than 10% of patients with the disorder. It is important that nurses are able to assess and treat patients effectively in the neonatal period with a diagnosis of osteogenesis imperfecta Type VIII using a multi-disciplinary approach. However, this fairly new classification of heritable bone disorders is extremely severe in nature and few cases have been reported in the literature. Therefore, the purpose of this case report is to describe a rare case of neonatal osteogenesis imperfecta type VIII and the multi-disciplinary approach required to manage the patient’s care. Institutional Review Board approval was obtained for the retrospective chart review utilized to present this report. To protect the identity of the neonate and family the name of the child will not be displayed and dates will be not be utilized.
Case presentation An African American male was delivered at 39.1 weeks of gestation to a gravida three para one, 23 year-old female. His birth weight was 3373 gm (3e5th %), head circumference 34.5 cm (10th %), and his length was not obtained due to difficulty, secondary to his abnormal skeletal structure. The neonate was born by cesarean section due to multiple in utero fractures and bowing identified by prenatal ultrasound. His APGAR scores were seven and nine at one and 5 min consecutively. There was a three vessel cord. He remained in the newborn nursery for monitoring and evaluation, but required no intubation. On physical examination there was no obvious facial dysmorphia, no blue sclera, and no short neck. The patient also did not have a cleft lip or palate. His arms and legs were shortened, and he had circumferential fat pads. The right hip was flexed to the chest and was also dislocated. He was also noted to have long flexible fingers and toes. The genitourinary exam appeared normal. He also appropriately cried to stimulus. He was not manipulated extensively therefore his spine was not examined. Genetics was consulted due to the possibility of lethal skeletal dysplasia and a significant history of a previously affected female sibling born three years prior to this pregnancy. He was subsequently followed by a Geneticist and an Advanced Practice
S. Hines-Dowell et al. Nurse with a Genetics specialty. A skeletal survey and orthopedics consult were also ordered. The skeletal survey revealed “popcorn” like epiphyses. In addition, an echocardiogram revealed no evidence of pulmonary hypertension, a small patent foramen ovale with left to right shunting, and small patent ductus arteriosus with left to right shunting. He was discharged home with hospice care on his eighth day of life. He did well, until his twenty-first day of life when he developed a cough and respiratory distress. He was then taken to the emergency department for evaluation and was admitted to the pediatric intensive care unit for monitoring. At this time palliative care was consulted for goal clarification, and on the second day of this hospital admission he was intubated for respiratory distress. At that time, testing for influenza type A was positive. Due to extreme fragility and a high risk for fractures; splinting, immobilization, or bracing were not considered. The patient was ordered a Z-flow mattress to assist in positioning and to provide comfort. Palliative care was consulted for support, pain management, clarification of goals based on his parents’ wishes for his care and for code status discussion. He recovered from his viral infection but repeated attempts to extubate were unsuccessful. At nine months of age, he was discharged home on ventilator support. Currently, he remains at home. He has no evidence of subsequent fractures, and is attaining some developmental milestones with saying “dada”, lifting his shoulders from his bed, reaching and holding toys, and he is able to be held and rocked without evidence of pain or discomfort. The palliative care team was involved early after discharge with home visits to assess pain with the patient’s parents and hospice nursing staff. This has since been transitioned to hospice and the primary pediatrician to allow those therapeutic relationships to develop. The child’s full female sibling was confirmed postmortem by DNA analysis to have two heterozygous for mutations in LEPRE1, the gene that encodes prolyl-3-hydroxylase 1 (P3H1). These mutations are consistent with the clinical diagnosis of osteogenesis imperfecta type VIII. The African American male child being examined was also tested by DNA and was found to carry the same two heterozygous mutations in LEPRE1 gene. The splice site mutation identified in this family has been seen in several African American families and originates in West Africa. The second mutation found in both siblings has not been reported in other families but is expected to result in very unstable mRNA and no protein product. According to Baldridge et al. (2008) the clinical features resulting from CRTAP or LEPRE1 loss of function mutations are difficult to distinguish
Case study at birth due to varying phenotypes. The precise mechanisms by which these mutations are translated into clinical phenotypes remain to be identified. Osteogenesis imperfecta type VIII is a recessive disorder therefore, the recurrence risk for the parents with each pregnancy is 25% (1 out of 4). Parents were counseled regarding the availability of prenatal testing with any subsequent pregnancies. A multi-disciplinary approach is required in order to meet these goals and to adapt treatment needs to the disease severity and the patient’s age (Monti et al., 2010).
Discussion According to Bishop (2010) frequent follow up is needed in the early stages of the diagnosis in order to help the family address the patient’s daily needs such as feeding, positioning and handling. Treating children with osteogenesis imperfecta is a very difficult task for providers and family members who care for them. The main goal for treatment should be focused on providing the best functions for long-term care as well as the most autonomy possible while minimizing fractures and deformities. Care should focus on keeping the patient as comfortable as possible while minimizing pain and allowing the patient to achieve independence in completing day-to-day activities. The plan of care for patients with osteogenesis imperfecta could also include a combination of both surgical and non-surgical treatments and rehabilitation. Surgical interventions may include fracture repair with the use of rods. Non-surgical interventions may include pharmaceutical therapy or bracing. The role of bracing in the treatment of osteogenesis imperfecta is limited as the deformed bones are generally not improved permanently by bracing. Bracing may be more uncomfortable for these patients and may cause more problems (Shapiro and Sponseller, 2009). Rehabilitation initially consists of proper positioning and handling and is followed up with formal exercises focusing on function and strength. The main goals of rehabilitation should focus on improving motor development, strength of muscles and joint range of motion, contracture prevention, and enhancing functional ability. At times the optimal, essential and compassionate care of children requires more than surgical and non-surgical interventions. Palliative care may be necessary. According to the American Academy of Pediatrics, “the goal of palliative care is to improve the child’s quality of life, and the aim is to add life to the child’s years, not simply years to the child’s life” (Foster, 2007, p. 215). There is
219 every reason to integrate palliative care into the mainstream of medical treatment of all children suffering from chronic, life-threatening, and life-limiting illnesses such as osteogenesis imperfecta type VIII, regardless of the curative intent of therapy. Palliative care provides an alternative to interventional therapy and is often preferred. A multi-disciplinary approach is essential in the management of patients with osteogenesis imperfecta to improve patient outcomes (Arundel and Bishop, 2010; Hackley and Merritt, 2008). In conjunction with the medical and pharmaceutical staff, Registered Nurses and Advanced Practice Nurses from multiple disciplines were involved in the care of this patient. Advanced Practice Nurses in neonatology, genetics, orthopedics, and palliative care all had an intricate role in the care of the patient with osteogenesis imperfecta type VIII. The nurse’s role as patient advocate and educator are vital among these disciplines (Hackley and Merritt, 2008). Therefore, the necessity for case reports that describe clinical findings in patients with osteogenesis imperfecta type VIII are required to enhance patient care and teaching.
Conclusion Osteogenesis imperfecta type VIII is a rare disorder, so as patients present with this disorder, healthcare providers can utilize new cases to build on the current literature available to gain a better understanding of the disease process. This is important because the healthcare provider is faced with a difficult challenge to identify and diagnose osteogenesis imperfecta type VIII using a very detailed physical assessment and extensive and accurate history (Hackley and Merritt, 2008). In addition, the nurse plays a vital role in providing safe and effective care, advocating for the patient and family, and providing education to improve patient outcomes. It is important to continue to examine new neonatal cases of osteogenesis imperfecta type VIII as they develop, to contribute to the nursing literature. Our case report provides valuable findings to assist the nurse by describing the clinical presentation of osteogenesis imperfecta type VIII and highlighting the multi-disciplinary approach warranted for treating this disorder in the neonate.
Acknowledgements To the patient and family, Dr. Eniko Pivnick, Dr. Jewell Ward, and Dr. Melody Cunningham.
220
S. Hines-Dowell et al.
References Arundel, P., Bishop, N., 2010. Diagnosing osteogenesis imperfecta. Pediatrics and Child Health 20 (5), 225e231. Baldridge, D., Schwarze, U., Morello, R., Lennington, J., et al., 2008. CRTAP and LEPRE1 mutations in recessive osteogenesis imperfecta. Human Mutation 29 (12), 1435e1442. Bishop, N., 2010. Characterising and treating osteogenesis imperfecta. Early Human Development 86 (11), 743e746. Cabral, W., Chang, W., Barnes, A., Weis, M., et al., 2007. Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta. National Genetics 39 (3), 359e365.
Dijk, V., Pals, G., Van Rijn, R., Nikkels, P., et al., 2010. Classification of osteogenesis imperfecta revisited. European Journal of Medical Genetics 53 (1), 1e5. Foster, T.L., 2007. Pediatric palliative care revisited: a vision to add life. Journal of Hospice & Palliative Nursing 9, 212e219. Hackley, L., Merritt, L., 2008. Osteogenesis imperfecta in the neonate. Advances in Neonatal Care 8 (1), 21e30. Kocher, M., Shapiro, F., 1998. Osteogenesis imperfecta. Journal of the American Academy of Orthpaedic Surgeons 6 (4), 224. Monti, E., Mottes, M., Fraschini, P., Brunelli, P., Forlino, A., Venturi, G., et al., 2010. Current and emerging treatments for the management of osteogenesis imperfecta. Therapeutics and Clinical Risk Management 6, 367e381. Shapiro, J., Sponseller, P., 2009. Osteogenesis imperfecta: questions and answers. Current Opinion in Pediatrics 21 (6), 709e716.
Available online at www.sciencedirect.com
www.elsevier.com/jneo
Osteogenesis imperfecta type VIII: A case report Stacy Hines-Dowell b, Shirleatha Lee a,*, Susie Baskin b, Ana Janecek b, Leslie Rhodes b, Flotyl Gresham b a
The University of Memphis, Newport Hall 210, 610 Goodman, Memphis, TN 38152, USA University of TN Le Bonheur Pediatric Specialist (ULPS), Le Bonheur Children’s Hospital, Memphis, TN, USA
b
Available online 3 December 2011
KEYWORDS Osteogenesis; Imperfecta; Bone; Genetic
Abstract Osteogenesis imperfecta is a genetic bone disorder that requires a multi-disciplinary healthcare team to achieve optimal patient outcomes. It is most recognized by excessive brittleness of the bones, and has several classification types, with varying levels of severity. In 2007, type VIII was added to the classification system as a severely deforming and lethal autosomal recessive gene associated with mutations of CRTAP and LEPRE1 genes. The purpose of this case report is to describe a rare case of osteogenesis imperfecta type VIII in the neonate and the multi-disciplinary approach required to manage the patient’s care; that includes a variety of nursing specialties. ª 2011 Neonatal Nurses Association. Published by Elsevier Ltd. All rights reserved.
Introduction This case report describes the multi-disciplinary care of a neonatal patient diagnosed with osteogenesis imperfecta type VIII. Osteogenesis imperfecta is a rare group of heritable metabolic bone disorders characterized by varying degrees of skeletal fragility (Kocher and Shapiro, 1998). It is the most common genetic disorder of the bones with wide-ranging clinical presentations (Monti et al., 2010). Because of the various clinical
* Corresponding author. Tel.: þ1 901 678 2036. E-mail address: [email protected] (S. Lee).
presentations of osteogenesis imperfecta, there are several systems of classification. The original classification system was proposed by Sillence and colleagues in 1979 and has continued to expand over the years with the discovery of new information about the disorder (Arundel and Bishop, 2010). In 2007, the identification of specific clinical features and differences in genetic mutations among some patients with osteogenesis imperfecta led to a proposal to add type VIII to the osteogenesis imperfecta classification system (Dijk et al., 2010). This proposal by Cabral and colleagues was made based on the identification of mutations due to LEPRE1 in patients with osteogenesis imperfecta (Cabral et al., 2007).
1355-1841/$ - see front matter ª 2011 Neonatal Nurses Association. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jnn.2011.11.009
218 Shapiro and Sponseller (2009) classify osteogenesis imperfecta Type VIII as a severe and lethal autosomal recessive gene associated with mutations of CRTAP and LEPRE1 genes that primarily affects South African blacks. The clinical presentation of patients with osteogenesis imperfecta type VIII is one of severe growth and mineralization deficiencies and accounts for fewer than 10% of patients with the disorder. It is important that nurses are able to assess and treat patients effectively in the neonatal period with a diagnosis of osteogenesis imperfecta Type VIII using a multi-disciplinary approach. However, this fairly new classification of heritable bone disorders is extremely severe in nature and few cases have been reported in the literature. Therefore, the purpose of this case report is to describe a rare case of neonatal osteogenesis imperfecta type VIII and the multi-disciplinary approach required to manage the patient’s care. Institutional Review Board approval was obtained for the retrospective chart review utilized to present this report. To protect the identity of the neonate and family the name of the child will not be displayed and dates will be not be utilized.
Case presentation An African American male was delivered at 39.1 weeks of gestation to a gravida three para one, 23 year-old female. His birth weight was 3373 gm (3e5th %), head circumference 34.5 cm (10th %), and his length was not obtained due to difficulty, secondary to his abnormal skeletal structure. The neonate was born by cesarean section due to multiple in utero fractures and bowing identified by prenatal ultrasound. His APGAR scores were seven and nine at one and 5 min consecutively. There was a three vessel cord. He remained in the newborn nursery for monitoring and evaluation, but required no intubation. On physical examination there was no obvious facial dysmorphia, no blue sclera, and no short neck. The patient also did not have a cleft lip or palate. His arms and legs were shortened, and he had circumferential fat pads. The right hip was flexed to the chest and was also dislocated. He was also noted to have long flexible fingers and toes. The genitourinary exam appeared normal. He also appropriately cried to stimulus. He was not manipulated extensively therefore his spine was not examined. Genetics was consulted due to the possibility of lethal skeletal dysplasia and a significant history of a previously affected female sibling born three years prior to this pregnancy. He was subsequently followed by a Geneticist and an Advanced Practice
S. Hines-Dowell et al. Nurse with a Genetics specialty. A skeletal survey and orthopedics consult were also ordered. The skeletal survey revealed “popcorn” like epiphyses. In addition, an echocardiogram revealed no evidence of pulmonary hypertension, a small patent foramen ovale with left to right shunting, and small patent ductus arteriosus with left to right shunting. He was discharged home with hospice care on his eighth day of life. He did well, until his twenty-first day of life when he developed a cough and respiratory distress. He was then taken to the emergency department for evaluation and was admitted to the pediatric intensive care unit for monitoring. At this time palliative care was consulted for goal clarification, and on the second day of this hospital admission he was intubated for respiratory distress. At that time, testing for influenza type A was positive. Due to extreme fragility and a high risk for fractures; splinting, immobilization, or bracing were not considered. The patient was ordered a Z-flow mattress to assist in positioning and to provide comfort. Palliative care was consulted for support, pain management, clarification of goals based on his parents’ wishes for his care and for code status discussion. He recovered from his viral infection but repeated attempts to extubate were unsuccessful. At nine months of age, he was discharged home on ventilator support. Currently, he remains at home. He has no evidence of subsequent fractures, and is attaining some developmental milestones with saying “dada”, lifting his shoulders from his bed, reaching and holding toys, and he is able to be held and rocked without evidence of pain or discomfort. The palliative care team was involved early after discharge with home visits to assess pain with the patient’s parents and hospice nursing staff. This has since been transitioned to hospice and the primary pediatrician to allow those therapeutic relationships to develop. The child’s full female sibling was confirmed postmortem by DNA analysis to have two heterozygous for mutations in LEPRE1, the gene that encodes prolyl-3-hydroxylase 1 (P3H1). These mutations are consistent with the clinical diagnosis of osteogenesis imperfecta type VIII. The African American male child being examined was also tested by DNA and was found to carry the same two heterozygous mutations in LEPRE1 gene. The splice site mutation identified in this family has been seen in several African American families and originates in West Africa. The second mutation found in both siblings has not been reported in other families but is expected to result in very unstable mRNA and no protein product. According to Baldridge et al. (2008) the clinical features resulting from CRTAP or LEPRE1 loss of function mutations are difficult to distinguish
Case study at birth due to varying phenotypes. The precise mechanisms by which these mutations are translated into clinical phenotypes remain to be identified. Osteogenesis imperfecta type VIII is a recessive disorder therefore, the recurrence risk for the parents with each pregnancy is 25% (1 out of 4). Parents were counseled regarding the availability of prenatal testing with any subsequent pregnancies. A multi-disciplinary approach is required in order to meet these goals and to adapt treatment needs to the disease severity and the patient’s age (Monti et al., 2010).
Discussion According to Bishop (2010) frequent follow up is needed in the early stages of the diagnosis in order to help the family address the patient’s daily needs such as feeding, positioning and handling. Treating children with osteogenesis imperfecta is a very difficult task for providers and family members who care for them. The main goal for treatment should be focused on providing the best functions for long-term care as well as the most autonomy possible while minimizing fractures and deformities. Care should focus on keeping the patient as comfortable as possible while minimizing pain and allowing the patient to achieve independence in completing day-to-day activities. The plan of care for patients with osteogenesis imperfecta could also include a combination of both surgical and non-surgical treatments and rehabilitation. Surgical interventions may include fracture repair with the use of rods. Non-surgical interventions may include pharmaceutical therapy or bracing. The role of bracing in the treatment of osteogenesis imperfecta is limited as the deformed bones are generally not improved permanently by bracing. Bracing may be more uncomfortable for these patients and may cause more problems (Shapiro and Sponseller, 2009). Rehabilitation initially consists of proper positioning and handling and is followed up with formal exercises focusing on function and strength. The main goals of rehabilitation should focus on improving motor development, strength of muscles and joint range of motion, contracture prevention, and enhancing functional ability. At times the optimal, essential and compassionate care of children requires more than surgical and non-surgical interventions. Palliative care may be necessary. According to the American Academy of Pediatrics, “the goal of palliative care is to improve the child’s quality of life, and the aim is to add life to the child’s years, not simply years to the child’s life” (Foster, 2007, p. 215). There is
219 every reason to integrate palliative care into the mainstream of medical treatment of all children suffering from chronic, life-threatening, and life-limiting illnesses such as osteogenesis imperfecta type VIII, regardless of the curative intent of therapy. Palliative care provides an alternative to interventional therapy and is often preferred. A multi-disciplinary approach is essential in the management of patients with osteogenesis imperfecta to improve patient outcomes (Arundel and Bishop, 2010; Hackley and Merritt, 2008). In conjunction with the medical and pharmaceutical staff, Registered Nurses and Advanced Practice Nurses from multiple disciplines were involved in the care of this patient. Advanced Practice Nurses in neonatology, genetics, orthopedics, and palliative care all had an intricate role in the care of the patient with osteogenesis imperfecta type VIII. The nurse’s role as patient advocate and educator are vital among these disciplines (Hackley and Merritt, 2008). Therefore, the necessity for case reports that describe clinical findings in patients with osteogenesis imperfecta type VIII are required to enhance patient care and teaching.
Conclusion Osteogenesis imperfecta type VIII is a rare disorder, so as patients present with this disorder, healthcare providers can utilize new cases to build on the current literature available to gain a better understanding of the disease process. This is important because the healthcare provider is faced with a difficult challenge to identify and diagnose osteogenesis imperfecta type VIII using a very detailed physical assessment and extensive and accurate history (Hackley and Merritt, 2008). In addition, the nurse plays a vital role in providing safe and effective care, advocating for the patient and family, and providing education to improve patient outcomes. It is important to continue to examine new neonatal cases of osteogenesis imperfecta type VIII as they develop, to contribute to the nursing literature. Our case report provides valuable findings to assist the nurse by describing the clinical presentation of osteogenesis imperfecta type VIII and highlighting the multi-disciplinary approach warranted for treating this disorder in the neonate.
Acknowledgements To the patient and family, Dr. Eniko Pivnick, Dr. Jewell Ward, and Dr. Melody Cunningham.
220
S. Hines-Dowell et al.
References Arundel, P., Bishop, N., 2010. Diagnosing osteogenesis imperfecta. Pediatrics and Child Health 20 (5), 225e231. Baldridge, D., Schwarze, U., Morello, R., Lennington, J., et al., 2008. CRTAP and LEPRE1 mutations in recessive osteogenesis imperfecta. Human Mutation 29 (12), 1435e1442. Bishop, N., 2010. Characterising and treating osteogenesis imperfecta. Early Human Development 86 (11), 743e746. Cabral, W., Chang, W., Barnes, A., Weis, M., et al., 2007. Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta. National Genetics 39 (3), 359e365.
Dijk, V., Pals, G., Van Rijn, R., Nikkels, P., et al., 2010. Classification of osteogenesis imperfecta revisited. European Journal of Medical Genetics 53 (1), 1e5. Foster, T.L., 2007. Pediatric palliative care revisited: a vision to add life. Journal of Hospice & Palliative Nursing 9, 212e219. Hackley, L., Merritt, L., 2008. Osteogenesis imperfecta in the neonate. Advances in Neonatal Care 8 (1), 21e30. Kocher, M., Shapiro, F., 1998. Osteogenesis imperfecta. Journal of the American Academy of Orthpaedic Surgeons 6 (4), 224. Monti, E., Mottes, M., Fraschini, P., Brunelli, P., Forlino, A., Venturi, G., et al., 2010. Current and emerging treatments for the management of osteogenesis imperfecta. Therapeutics and Clinical Risk Management 6, 367e381. Shapiro, J., Sponseller, P., 2009. Osteogenesis imperfecta: questions and answers. Current Opinion in Pediatrics 21 (6), 709e716.
Available online at www.sciencedirect.com