BMJ 2014;349:g4514 doi: 10.1136/bmj.g4514 (Published 15 July 2014)
Page 1 of 2
Editorials
EDITORIALS What causes cerebral palsy? A genetic or familial component now looks likely Peter Rosenbaum professor of paediatrics and Canada Research Chair in Childhood Disability CanChild Centre for Childhood Disability Research, McMaster University, 1400 Main Street West, Hamilton ON, Canada L8S 1C7
What causes neurodisabilities such as cerebral palsy? This is one of the most challenging questions facing affected families and the health professionals who advise and care for people with these disparate conditions.
Traditionally, we believed that if a mother had a “difficult” delivery and a newborn adapted poorly to postnatal life and was subsequently found to have cerebral palsy, these events were causally linked. The cerebral palsy was intuitively connected to adverse preceding events, and doctors and other health professionals were easily blamed for poor care that supposedly led to the poor outcome. As perinatal medicine advanced with the aid of new technologies such as prenatal imaging,1 we have realised that impairments in brain development, structure, and function very often precede adverse perinatal or postnatal events, and may even “cause” them.
The original work by Tollånes and colleagues (doi:10.1136/bmj. g4294) takes advantage of a remarkable resource—the Medical Birth Registry of Norway, with its links to the Norwegian social insurance scheme—to explore the risk of recurrence (and perhaps heritability) of cerebral palsy in a cohort of more than two million Norwegians born between 1967 and 2002.2 The researchers identified graded levels of increased risk after the birth of an index child with cerebral palsy compared with the risk after the birth of an unaffected child. They report a 15-fold increased risk of cerebral palsy in a second twin, a ninefold increased risk for a full sibling of the index child, and a threefold increased risk in half siblings. They also identified smaller, but still discernible, increases in risk among more distant blood relatives of a child with cerebral palsy, such as first cousins. Cerebral palsy is not a specific genetically determined biomedical condition like Duchenne muscular dystrophy. The term encompasses a group of conditions that have in common an impairment in brain function or structure that causes an enduring impairment in the development of motor control, often (but not invariably) with additional central nervous system impairments such as epilepsy, learning disabilities, and sensory difficulties.3 What do the findings of Tollånes and colleagues add to the elusive search for the cause of cerebral palsy? Being a twin is a well recognised risk factor, probably related to a combination of high rates of prematurity among twins as well as the risk of
sharing an intrauterine environment in which the ill health of one twin can adversely affect the other.4 We also know that prematurity is a powerful risk factor for the development of cerebral palsy,5 as are maternal iodine deficiency and Rh incompatibility.6 7 The last two biomedical factors are essentially modifiable. Where appropriate antenatal screening and management are available to women at risk, these interventions have probably prevented many cases of cerebral palsy. Yet the incidence and prevalence of cerebral palsy in most countries has remained largely unchanged for several decades. The Norwegian study suggests that genes, a shared early familial environment, or perhaps both, are important contributors to overall risk, although many other as yet unidentified causative factors remain. Aetiology is important because parents rightly want to know why their child has serious neurological impairments, whether something they did caused their child’s problems, and whether the same problems may recur in later children or grandchildren. Doctors and counsellors want to understand what causes neurodisabilities such as cerebral palsy so they can devise and test interventions to help prevent it. Epidemiological studies such as the one by Tollånes and colleagues are the cornerstone of research into the causes of cerebral palsy. They record incidence and prevalence and look for patterns across and within communities and populations, taking account of the many possible contributors to the genesis of these impairments. For example, the role of cerebral malaria has been recognised in many parts of the world as a cause of permanent brain childhood impairment—opening up valuable opportunities for the primary prevention of cerebral palsy and epilepsy.8
In their thoughtful discussion, Tollånes and colleagues recognise the reality of the shared early environments of people who are closely related genetically, so that “genetic” explanations alone are unlikely to account for the increased risks observed within families. They also comment on “selective fertility”—the idea that non-biological factors such as limited opportunities for social relationships and sex may in turn limit the number of children born to adults with cerebral palsy. Given the slow but continuing improvements in the social lives of young adults with developmental impairments, including cerebral palsy,
Correspondence to: [email protected] For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
BMJ 2014;349:g4514 doi: 10.1136/bmj.g4514 (Published 15 July 2014)
Page 2 of 2
EDITORIALS
selective fertility may be a moving target and will repay further evaluation over the next few decades.
As adults with cerebral palsy have more opportunities to become biological parents, researchers will be able to explore inheritance with greater certainty. Even very large studies currently identify relatively small numbers of children born to affected parents. Despite its size, Tollånes and colleagues’ study included only 151 parents with cerebral palsy. They had a total of 237 children, and just two had the same condition. As this excellent study illustrates, the elusive search for the causes of neurodisabilities such as cerebral palsy is far from over. While we wait, however, we must remember that cerebral palsy remains a relatively infrequent occurrence at about 2 per 1000 live births in developed countries. As the authors note, even family members with a 15-fold increase in risk of recurrence have a small absolute risk of cerebral palsy. This information should provide some reassurance to families in which cerebral palsy is already present.
For personal use only: See rights and reprints http://www.bmj.com/permissions
Competing interests: I have read and understood the BMJ policy on competing interests and declare the following interests: None. Provenance and peer review: Commissioned; not externally peer reviewed. 1 2 3 4 5 6 7 8
Glenn OA. MR imaging of the fetal brain. Pediatr Radiol 2010;40:68-81. Tollånes M, Wilcox A, Lie RT, Mosher D. Familial risk of cerebral palsy: population based cohort study. BMJ 2014;349:g4294. Rosenbaum P, Paneth N, Leviton A, Goldstein M, Bax M, Damiano D, et al. A report: the definition and classification of cerebral palsy. Dev Med Child Neurol Suppl 2007;109:8-14. Grether JK, Nelson KB, Cummins SK. Twinning and cerebral palsy: experience in four northern California counties, births 1983 through 1985. Pediatrics 1993;92:854-8. Nelson KB. Causative factors in cerebral palsy. Clin Obstet Gynecol 2008;51:749-62. Hong T, Paneth N. Maternal and infant thyroid disorders and cerebral palsy. Semin Perinatol 2008;32:438-45. Zipursky A, Israels LG. The pathogenesis and prevention of Rh immunization. Can Med Assoc J 1967;97:1245-7. Idro R, Marsh K, John CC, Newton CR. Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome. Pediatr Res 2010;68:267-74.
Cite this as: BMJ 2014;349:g4514 © BMJ Publishing Group Ltd 2014
Subscribe: http://www.bmj.com/subscribe
Page 1 of 2
Editorials
EDITORIALS What causes cerebral palsy? A genetic or familial component now looks likely Peter Rosenbaum professor of paediatrics and Canada Research Chair in Childhood Disability CanChild Centre for Childhood Disability Research, McMaster University, 1400 Main Street West, Hamilton ON, Canada L8S 1C7
What causes neurodisabilities such as cerebral palsy? This is one of the most challenging questions facing affected families and the health professionals who advise and care for people with these disparate conditions.
Traditionally, we believed that if a mother had a “difficult” delivery and a newborn adapted poorly to postnatal life and was subsequently found to have cerebral palsy, these events were causally linked. The cerebral palsy was intuitively connected to adverse preceding events, and doctors and other health professionals were easily blamed for poor care that supposedly led to the poor outcome. As perinatal medicine advanced with the aid of new technologies such as prenatal imaging,1 we have realised that impairments in brain development, structure, and function very often precede adverse perinatal or postnatal events, and may even “cause” them.
The original work by Tollånes and colleagues (doi:10.1136/bmj. g4294) takes advantage of a remarkable resource—the Medical Birth Registry of Norway, with its links to the Norwegian social insurance scheme—to explore the risk of recurrence (and perhaps heritability) of cerebral palsy in a cohort of more than two million Norwegians born between 1967 and 2002.2 The researchers identified graded levels of increased risk after the birth of an index child with cerebral palsy compared with the risk after the birth of an unaffected child. They report a 15-fold increased risk of cerebral palsy in a second twin, a ninefold increased risk for a full sibling of the index child, and a threefold increased risk in half siblings. They also identified smaller, but still discernible, increases in risk among more distant blood relatives of a child with cerebral palsy, such as first cousins. Cerebral palsy is not a specific genetically determined biomedical condition like Duchenne muscular dystrophy. The term encompasses a group of conditions that have in common an impairment in brain function or structure that causes an enduring impairment in the development of motor control, often (but not invariably) with additional central nervous system impairments such as epilepsy, learning disabilities, and sensory difficulties.3 What do the findings of Tollånes and colleagues add to the elusive search for the cause of cerebral palsy? Being a twin is a well recognised risk factor, probably related to a combination of high rates of prematurity among twins as well as the risk of
sharing an intrauterine environment in which the ill health of one twin can adversely affect the other.4 We also know that prematurity is a powerful risk factor for the development of cerebral palsy,5 as are maternal iodine deficiency and Rh incompatibility.6 7 The last two biomedical factors are essentially modifiable. Where appropriate antenatal screening and management are available to women at risk, these interventions have probably prevented many cases of cerebral palsy. Yet the incidence and prevalence of cerebral palsy in most countries has remained largely unchanged for several decades. The Norwegian study suggests that genes, a shared early familial environment, or perhaps both, are important contributors to overall risk, although many other as yet unidentified causative factors remain. Aetiology is important because parents rightly want to know why their child has serious neurological impairments, whether something they did caused their child’s problems, and whether the same problems may recur in later children or grandchildren. Doctors and counsellors want to understand what causes neurodisabilities such as cerebral palsy so they can devise and test interventions to help prevent it. Epidemiological studies such as the one by Tollånes and colleagues are the cornerstone of research into the causes of cerebral palsy. They record incidence and prevalence and look for patterns across and within communities and populations, taking account of the many possible contributors to the genesis of these impairments. For example, the role of cerebral malaria has been recognised in many parts of the world as a cause of permanent brain childhood impairment—opening up valuable opportunities for the primary prevention of cerebral palsy and epilepsy.8
In their thoughtful discussion, Tollånes and colleagues recognise the reality of the shared early environments of people who are closely related genetically, so that “genetic” explanations alone are unlikely to account for the increased risks observed within families. They also comment on “selective fertility”—the idea that non-biological factors such as limited opportunities for social relationships and sex may in turn limit the number of children born to adults with cerebral palsy. Given the slow but continuing improvements in the social lives of young adults with developmental impairments, including cerebral palsy,
Correspondence to: [email protected] For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
BMJ 2014;349:g4514 doi: 10.1136/bmj.g4514 (Published 15 July 2014)
Page 2 of 2
EDITORIALS
selective fertility may be a moving target and will repay further evaluation over the next few decades.
As adults with cerebral palsy have more opportunities to become biological parents, researchers will be able to explore inheritance with greater certainty. Even very large studies currently identify relatively small numbers of children born to affected parents. Despite its size, Tollånes and colleagues’ study included only 151 parents with cerebral palsy. They had a total of 237 children, and just two had the same condition. As this excellent study illustrates, the elusive search for the causes of neurodisabilities such as cerebral palsy is far from over. While we wait, however, we must remember that cerebral palsy remains a relatively infrequent occurrence at about 2 per 1000 live births in developed countries. As the authors note, even family members with a 15-fold increase in risk of recurrence have a small absolute risk of cerebral palsy. This information should provide some reassurance to families in which cerebral palsy is already present.
For personal use only: See rights and reprints http://www.bmj.com/permissions
Competing interests: I have read and understood the BMJ policy on competing interests and declare the following interests: None. Provenance and peer review: Commissioned; not externally peer reviewed. 1 2 3 4 5 6 7 8
Glenn OA. MR imaging of the fetal brain. Pediatr Radiol 2010;40:68-81. Tollånes M, Wilcox A, Lie RT, Mosher D. Familial risk of cerebral palsy: population based cohort study. BMJ 2014;349:g4294. Rosenbaum P, Paneth N, Leviton A, Goldstein M, Bax M, Damiano D, et al. A report: the definition and classification of cerebral palsy. Dev Med Child Neurol Suppl 2007;109:8-14. Grether JK, Nelson KB, Cummins SK. Twinning and cerebral palsy: experience in four northern California counties, births 1983 through 1985. Pediatrics 1993;92:854-8. Nelson KB. Causative factors in cerebral palsy. Clin Obstet Gynecol 2008;51:749-62. Hong T, Paneth N. Maternal and infant thyroid disorders and cerebral palsy. Semin Perinatol 2008;32:438-45. Zipursky A, Israels LG. The pathogenesis and prevention of Rh immunization. Can Med Assoc J 1967;97:1245-7. Idro R, Marsh K, John CC, Newton CR. Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome. Pediatr Res 2010;68:267-74.
Cite this as: BMJ 2014;349:g4514 © BMJ Publishing Group Ltd 2014
Subscribe: http://www.bmj.com/subscribe
