Epidemiology of holoprosencephaly and phenotypic characteristics of affected children: New York state, 1984–1989

Abstract

Holoprosencephaly is a congenital defect of the median structures of the brain and face. The epidemiology is poorly known due to the paucity of population-based studies. This study describes the epidemiology of holoprosencephaly in a large population, using cases identified through the New York State Congenital Malformations Registry, and born in 1984-1989. We describe the craniofacial abnormalities present, their frequency, and their cooccurrence, and we examine the correspondence between the severity of craniofacial abnormalities, chromosomal abnormalities, and severity of the brain defect. Liveborn cases totaled 78, yielding a prevalence of 4.8 per 100,000 live births. Prevalence among girls was nearly double that in boys, and was 4.2 times higher among infants of mothers under age 18 compared to infants of older mothers. Only 9.8% of all cases had no craniofacial abnormalities other than the brain defect. Eye malformations were present in 76.8%, nose malformations in 69.5%, ear malformations in 50%, and oral clefts in 41.5%. These malformations arise at different times during gestation. The variability in patterns of cooccurrence suggests variability in the developmental pathways and/or timing of developmental derangements which result in holoprosencephaly. This, in turn, is consistent with a model of multiple causes. Children with alobar holoprosencephaly tended to have the most severe craniofacial anomalies, but the correspondence was not 100%. Craniofacial phenotype does not consistently discriminate between cytogenetically normal and abnormal cases.

Disorders of prosencephalic development

“…The identified causes are chromosomal, monogenic, and teratogenic. Chromosomal abnormalities are present in 24 to 47% of all cases Table 7) Autosomal recessive X-linked Non syndromic HPE (See Table 6 (Croen et al, 1996;Olsen et al, 1997;Bullen et al, 2001;Ong et al, 2007), most commonly trisomy 13. Monogenic inheritance of non-syndromic HPE (Table 6) includes most commonly autosomal dominant transmission with variable expressivity and incomplete penetrance; autosomal recessive transmission and X-linked transmission have been also reported.…”

“…-Approximately 50% of children with alobar HPE die before age four to five months and 20% live past the first year of life (Barr and Cohen, 1999). -More than 50% of children with isolated semilobar or lobar HPE without associated significant malformations of other organs are alive at age 12 months (Olsen et al, 1997;Barr and Cohen, 1999). Almost all have apparently normal vision and hearing (Barr and Cohen, 1999).…”

Targeted Disruption of Tgif, the Mouse Ortholog of a Human Holoprosencephaly Gene, Does Not Result in Holoprosencephaly in Mice

“…HPE is the most common congenital malformation of the developing human forebrain, in which the two cerebral hemispheres fail to separate and the two lateral ventricles are fused into one (13,30,39,41). Heterozygous nonsense and missense mutations in the genes SIX3, SHH, TGIF, ZIC2, and PTCH have been identified to be responsible for familial HPE2, HPE3, HPE4, HPE5, and HPE7, respectively (3,7,16,33,47).…”

Holoprozensefali: Bir Olgu Sunumu

“…Ağır holoprozensefalide, tek bir göz (siklopi) ve tek burun deliği (sebosefali), burnun gözlerin ortasında yer alması (etmosefali), premaksillanın agenezi ve fasiyal dismorfik bulgular saptanırken, daha hafif olgularda ise mikrosefali, mental retardasyon, oküler hipoteleorizm, dudak damak yarığı ve tek maksiller santral kesici diş gözlenen bulgular arasındadır (3,6,7,8). Holoprozensefalinin prognozu, hastalığın tipine ve ilgili anomalilerin varlığına bağlı olarak değişmektedir.…”