McKusick-Kaufman syndrome is a human developmental anomaly syndrome comprising 
mesoaxial or postaxial polydactyly, congenital heart disease and 
hydrometrocolpos. This syndrome is diagnosed most frequently in the Old Order 
Amish population and is inherited in an autosomal recessive pattern with reduced 
penetrance and variable expressivity. Homozygosity mapping and linkage analyses 
were conducted using two pedigrees derived from a larger pedigree published in 
1978. The PedHunter software query system was used on the Amish Genealogy 
Database to correct the previous pedigree, derive a minimal pedigree connecting 
those affected sibships that are in the database and determine the most recent 
common ancestors of the affected persons. Whole genome short tandem repeat 
polymorphism (STRP) screening showed homozygosity in 20p12, between D20S162 and 
D20S894 , an area that includes the Alagille syndrome critical region. The peak 
two-point LOD score was 3.33, and the peak three-point LOD score was 5.21. The 
physical map of this region has been defined, and additional polymorphic markers 
have been isolated. The region includes several genes and expressed sequence 
tags (ESTs), including the jagged1 gene that recently has been shown to be 
haploinsufficient in the Alagille syndrome. Sequencing of jagged1 in two 
unrelated individuals affected with McKusick-Kaufman syndrome has not revealed 
any disease-causing mutations.