Polygenic threshold model with sex dimorphism in adolescent idiopathic scoliosis: the Carter effect

Adolescent idiopathic scoliosis occurs between two and ten times more frequently in females than in males. The exact cause of this sex discrepancy is unknown, but it may represent a difference in susceptibility to the deformity. If this difference is attributable to genetic factors, then males with adolescent idiopathic scoliosis would need to inherit a greater number of susceptibility genes compared with females to develop the deformity. Males would also be more likely to transmit the disease to their children and to have siblings with adolescent idiopathic scoliosis. Such a phenomenon is known as the Carter effect, and the presence of such an effect would support a multifactorial threshold model of inheritance.

One hundred and forty multiplex families in which more than one individual was affected with adolescent idiopathic scoliosis were studied. These families contained 1616 individuals, including 474 individuals with adolescent idiopathic scoliosis and 1142 unaffected relatives. The rates of transmission from the 122 affected mothers and from the twenty-eight affected fathers were calculated, and the prevalence among siblings was determined in the nuclear families of affected individuals.

The prevalence of adolescent idiopathic scoliosis in these multiplex families was lowest in sons of affected mothers (36%, thirty-eight of 105) and highest in daughters of affected fathers (85%, twenty-two of twenty-six). Affected fathers transmitted adolescent idiopathic scoliosis to 80% (thirty-seven) of forty-six children, whereas affected mothers transmitted it to 56% (133) of 239 children (p < 0.001). Siblings of affected males also had a significantly higher prevalence of adolescent idiopathic scoliosis (55%, sixty-one of 110) compared with siblings of affected females (45%, 206 of 462) (p = 0.04).

This study demonstrates the presence of the Carter effect in adolescent idiopathic scoliosis. This pattern can be explained by polygenic inheritance of adolescent idiopathic scoliosis, with a greater genetic load required for males to be affected.