STUDY DESIGN: A cohort of 145 patients with adolescent idiopathic scoliosis 
(AIS) were identified and contacted to determine whether they had a family 
history of scoliosis. These results were submitted to an internal genealogical 
database to screen for potential connections to other AIS families. The severity 
and incidence of AIS in extended family groups were also analyzed.
OBJECTIVES: Our objectives were to quantify the genetic effect in AIS, determine 
the expressivity and penetrance of AIS in large family groupings, and examine 
larger scoliosis pedigrees for evidence of multiple genes.
SUMMARY OF BACKGROUND DATA: Previous reports have suggested an 80% connectedness 
among scoliosis families, but no clear evidence of multiple genes. It is not 
known if there are major gene(s).
METHODS: A cohort of 145 AIS probands were identified and contacted to ascertain 
whether they had a family history of AIS. Their medical records and spine 
radiographs were reviewed to confirm the diagnosis and determine the disease 
severity. Using an internal genealogical database, the cases were screened for 
potential connections that would produce larger extended pedigrees.
RESULTS: Overall, 131 of the probands were in the database and 127 showed 
connections to other scoliosis families, a 97% connectedness. These results 
suggest a major scoliosis gene, as more than 50% of the probands were connected 
by founders that all resided in England in the mid 1500s. The differences in 
penetrance (41% vs. 34%) and expressivity (38% vs. 61%) between seemingly 
unrelated large family groupings might suggest that two different genes are a 
major influence for AIS in these families.
CONCLUSIONS: Nearly all (97%) AIS patients have familial origins. There appears 
to be at least one major gene, and the differences in penetrance and 
expressivity in two large unconnected pedigrees might suggest the presence of 
more than one gene.