title: A retrospective survey of perinatal risk factors of 104 living children with holoprosencephaly.
abstract: Holoprosencephaly (HPE) is a brain malformation resulting from a primary defect in development of the basal forebrain during early gestation. Prenatal genetic and environmental factors and birth outcomes were described in a population of 104 children with holoprosencephaly referred to three clinical centers from 1998 through 2002. The mean child age was 4 years. Of cases karyotyped, 9% presented with a chromosomal abnormality. This study of living children with holoprosencephaly, the majority of whom are cytogenetically normal, provides new information on the subsample of children with a less severe phenotype. Most children were born at term; about 51% were microcephalic at birth. Consistent with previous research, the association between HPE and maternal history of diabetes merits further investigation. Several findings have important implications for future research. Only 22% of the children in this study sample were diagnosed with holoprosencephaly prenatally. The vast majority of children (72%) were diagnosed with HPE between birth and 1 year of age. Also, 19% of the cases referred to the Carter Centers with HPE were not confirmed on scan review. When possible, future population-based epidemiological studies should emphasize mechanisms that identify children with HPE outside of the newborn period and confirm the diagnosis by review of MRI or high quality CT brain scan.
authors.affiliation: Department of Neurology and Developmental Medicine, Kennedy Krieger Institute and Johns Hopkins University, Baltimore, Maryland 21205, USA. stashinko@kennedykrieger.org
authors.forename: Elaine E
authors.initials: EE
authors.lastname: Stashinko
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Clegg
authors.forename: Heather A
authors.initials: HA
authors.lastname: Kammann
authors.forename: Vicki T
authors.initials: VT
authors.lastname: Sweet
authors.forename: Mauricio R
authors.initials: MR
authors.lastname: Delgado
authors.forename: Jin S
authors.initials: JS
authors.lastname: Hahn
authors.forename: Eric B
authors.initials: EB
authors.lastname: Levey
mesh_terms: D000293:Adolescent; D001921:Brain / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D004777:Environment; D005260:Female; D005865:Gestational Age; D016142:Holoprosencephaly / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D008831:Microcephaly / Q000453:epidemiology; D010641:Phenotype; D011247:Pregnancy; D011256:Pregnancy Outcome; D011295:Prenatal Care; D011296:Prenatal Diagnosis; D016548:Prosencephalon / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016216:Ultrasonography, Prenatal