How is familial idiopathic scoliosis transmitted? Analysis of 26 pedigrees

Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of the spine, affecting 1-3 % of the population, predominantly female patients, especially for severe curves. Its etiology is still debated, but a genetic involvement is certain, alongside with epigenetic and environmental factors. Isolated or sporadic cases are frequent, but AIS also affect families, with a reported heritability up to 38%.

The main hypothesis of this study was that a particular form of AIS, familial AIS, displays specific forms of transmission, linked to gender.

Pedigree of 26 families with at least 2 confirmed cases of AIS were studied in affected individuals, as well as the absence of scoliosis signs in healthy relatives. The prevalence of AIS was calculated after correction for bias. The transmission was first analyzed globally, then according to the gender of the affected parents and children.

26 families were included, consisting of 94 patients affected with AIS, adjusted to 66 patients and 160 healthy relatives in the analysis corrected by the proband method, for a prevalence of 29.2%. The transmission of AIS was higher to daughters (49%) than to sons (17%) of affected parent, suggesting a Carter effect (differential transmission according to the gender). Moreover, out of 66 AIS patients in the proband-adjusted analysis, 49 (74.2%) were female and 17 (25.8%) male (ratio = 3), demonstrating the higher penetrance in female for familial AIS.

This study underlines an autosomic dominant mode of inheritance in familial idiopathic scoliosis, with an incomplete penetrance (transmission rate <50%). Clinicians should be aware of a specific form of familial AIS, to counsel families.

IV; Prognostic study.