A study published in the Journal of Bone and Joint Surgery (USA) indicates that men with scoliosis are 3.28 times more likely to transmit scoliosis to their children than women with scoliosis, demonstrating the possibility of the Carter effect in adolescent idiopathic scoliosis.
Lisa Kruse, Department of Orthopaedic Surgery, Washing University School of Medicine, St Louis, and others reported that the “Carter effect” is a genetic model in which males need to inherit a greater number of susceptible genes or risk factors to develop a specific trait. They added that there is evidence that the Carter effect is present in adolescent idiopathic scoliosis (AIS) because the female to male ratio for scoliosis ranges from 2:1 to 10:1. Kruse et al reported: “We hypothesised that adolescent idiopathic scoliosis is a disease with multigenetic, multifactorial, inheritance in which males require a higher genetic and environmental load to be affected.” They explained that if a Carter effect was present in AIS, there would be a higher rate of AIS in children and siblings of affected males than of affected females.
Kruse et al evaluated data for 140 families in which more than one member was affected by AIS. They found that fathers transmitted AIS to 80.4% of their children but affected mothers only transmitted AIS to 55.6% of their children. The investigators reported: “Assessed on the basis of the odds ratio, an affected father was 3.28 more likely to than an affected mother to have an affected child.”
After analysing female children separately, Kruse et al found that the risk of transmission did not significantly differ between affected mothers and daughters and affected fathers and daughters. However, the risk of transmission was significantly higher in affected fathers and sons than in affected mothers and sons. Kruse et al wrote: “This represents a 5.29-fold increased risk of AIS to males from affected fathers compared with affected mothers.”
In the study, the authors also reviewed the prevalence of AIS in siblings of affected individuals. They found that siblings of an affected male had a 1.55-fold increased risk of AIS than a sibling of an affected female. Additionally, they found that compared with sisters of affected females, sisters of affected males had a 2.26-fold increased risk of AIS and brothers of affected males had a 2.49 increased risk compared with brothers of affected females.
Kruse et al commented that their data would be “useful in monitoring children and siblings of affected individuals and in advising families regarding the risk of their other children developing AIS.” However, they added their data could potentially “inflate the overall risk” to siblings and children of individuals with AIS because it excluded families in which only one member was affected by the condition.
In an accompanying editorial, William Cole (University of Alberta, Edmonton, Canada) said that Kruse et al’s study “offers some exciting possibilities” for ongoing studies to characterise the underlying genetic variants that account for the different malformation thresholds in men and women. He added: “Further genetic analysis, based on the report by Kruse et al, and those by other investigators, may reveal genetic variants in signalling or other pathways that suppress the progression and severity of AIS.”
Study author Christina Gurnett, associate professor, Department of Neurology, Division Pediatric Neurology Washington University School of Medicine, St Louis, USA, told Spinal News International: “Our study solidifies the evidence in favour of polygenic inheritance of adolescent idiopathic scoliosis. Fortunately, we are now poised with new genetic techniques that will allow us to investigate the role for both common and rare genetic variants in scoliosis aetiology. Once we understand the various pathways that lead to the development and progression of scoliosis, we can provide better counselling and treatment for these patients.”