Search for genomic imbalances in a cohort of 20 patients with oral–facial–digital syndromes negative for mutations and large rearrangements in the OFD1 gene

Oral–facial–digital syndromes (OFDS) are characterized by theassociation of abnormal clinical features affecting the face(hypertelorism, epicanthic folds and/or down-slanting palpebralfissures, pseudocleft of the upper lip, cleft lip), the mouth (highlyarchedpalate,cleftpalate,oralfrenula,lingualhamartoma,bifidorcleft tongue, and/or tooth abnormalities), and the digits(brachydactyly,polydactyly,syndactyly,and/orclinodactylyofthehand and/or the feet). Other organ systems can be involved,defining a complex nosology including 13 specific subtypes ofOFDS [Gurrieri et al., 2007]. Types I and II are the most frequentOFDS.OFDIischaracterizedbyanX-linkeddominantinheritance,frequent renal polycystic disease, and corpus callosum agenesis[Donnai et al., 1987; Odent et al., 1998]. OFD VII is consideredidenticaltoOFDI[Nowaczyketal.,2003].OFDIIischaracterizedby frequent bilateral polysyndactyly of the halluces and autosomalrecessive inheritance [Gurrieri et al., 2007]. Other rare OFDS aredistinguished by specific extra-OFD manifestations: ceaseless see-saw winking of the eyes and/or myoclonic jerks (OFD III), severetibial dysplasia (OFD IV), cerebellar malformations and recurrentY-shaped metacarpals (OFD VI), and retinal coloboma (OFD IX)[Gurrieri etal.,2007]. TheOFDS X, XI, XII, and XIII present withmultiplecongenitalabnormalities(MCA)andhavebeendescribedinonlyoneortworeports.Moreover,afewcaseshavebeenreported