Holoprosencephaly 1; Hpe1

Description

Holoprosencephaly (HPE) is the most common structural malformation of the human forebrain and occurs after failed or abbreviated midline cleavage of the developing brain during the third and fourth weeks of gestation. HPE occurs in up to 1 in 250 gestations, but only 1 in 8,000 live births (Lacbawan et al., 2009). Classically, 3 degrees of severity defined by the extent of brain malformation have been described. In the most severe form, 'alobar HPE,' there is a single ventricle and no interhemispheric fissure. The olfactory bulbs and tracts and the corpus callosum are typically absent. In 'semilobar HPE,' the most common type of HPE in neonates who survive, there is partial cortical separation with rudimentary cerebral hemispheres and a single ventricle. In 'lobar HPE,' the ventricles are separated, but there is incomplete frontal cortical separation (Corsello et al., 1990). An additional milder form, called 'middle interhemispheric variant' (MIHV) has also been delineated, in which the posterior frontal and parietal lobes are incompletely separated and the corpus callosum may be hypoplastic (Lacbawan et al., 2009). Finally, microforms of HPE include a single maxillary median incisor or hypotelorism without the typical brain malformations (summary by Mercier et al., 2011). Cohen (2001) discussed problems in the definition of holoprosencephaly, which can be viewed from 2 different perspectives: anatomic (fixed) and genetic (broad). When the main interest is description, the anatomic perspective is appropriate. In genetic perspective, a fixed definition of holoprosencephaly is not appropriate because the same mutational cause may result in either holoprosencephaly or some microform of holoprosencephaly. Cohen (2001) concluded that both fixed and broad definitions are equally valid and depend on context.Munke (1989) provided an extensive review of the etiology and pathogenesis of holoprosencephaly, emphasizing heterogeneity.See also schizencephaly (OMIM ), which may be part of the phenotypic spectrum of HPE. Genetic Heterogeneity of HoloprosencephalySeveral loci for holoprosencephaly have been mapped to specific chromosomal sites and the molecular defects in some cases of HPE have been identified. Holoprosencephaly-1 (HPE1) maps to chromosome 21q22. HPE2 (OMIM ), caused by mutation in the SIX3 gene (OMIM ), maps to 2p21. HPE3 (OMIM ), caused by mutation in the Sonic hedgehog gene (SHH ), maps to 7q36. HPE4 (OMIM ), caused by mutation in the TGIF gene (OMIM ), maps to 18p11. HPE5 (OMIM ), caused by mutation in the ZIC2 gene (OMIM ), maps to 13q32. HPE6 (OMIM ) maps to 2q37. HPE7 (OMIM ), caused by mutation in the PTCH1 gene (OMIM ), maps to 9q22. HPE8 (OMIM ) maps to 14q13. HPE9 (OMIM ), caused by mutation in the GLI2 gene (OMIM ), maps to 2q14. HPE10 (OMIM ) maps to 1q41-q42. HPE11 (OMIM ) is caused by mutation in the CDON gene (OMIM ) on chromosome 11q24.Wallis and Muenke (2000) gave an overview of mutations in holoprosencephaly. They indicated that at least 12 different loci had been associated with HPE.

Clinical Features

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia
• Microcephaly
• Strabismus
• Ptosis
• Low-set ears
• Hydrocephalus

And another 34 symptoms. If you need more information about this disease we can help you.