Holoprosencephaly (HPE) is a spectrum of brain and facial malformations primarily reflecting genetic factors, such
as chromosomal abnormalities and gene mutations. Here, we present a clinical and molecular analysis of 195
probands with HPE or microforms; approximately 72% of the patients were derived from the Latin American Collabo-rative Study of Congenital Malformations (ECLAMC), and 82% of the patients were newborns. Alobar HPE was the
predominant brain defect in almost all facial defect categories, except for patients without oral cleft and median or lat-eral oral clefts. Ethmocephaly, cebocephaly, and premaxillary agenesis were primarily observed among female pa-tients. Premaxillary agenesis occurred in six of the nine diabetic mothers. Recurrence of HPE or microform was
approximately 19%. The frequency of microdeletions, detected using Multiplex Ligation-dependant Probe Amplifica-tion (MLPA) was 17% in patients with a normal karyotype. Cytogenetics or QF-PCR analyses revealed chromosomal
anomalies in 27% of the probands. Mutational analyses in genesSHH,ZIC2,SIX3andTGIFwere performed in 119
patients, revealing eight mutations inSHH,two mutations inSIX3and two mutations inZIC2. Thus, a detailed clinical
description of new HPE cases with identified genetic anomalies might establish genotypic and phenotypic correla-tions and contribute to the development of additional strategies for the analysis of new cases
