Preferred Label : Holoprosencephaly 1;
Symbol : HPE1;
CISMeF acronym : HPEC; HPE1;
Type : Phenotype or locus, molecular basis unknown;
Alternative titles and symbols : Holoprosencephaly, familial alobar; CYCLOPIA; Hpe, familial; HPEC; Demyer sequence; ARHINENCEPHALY;
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 (269160), which may be part of the phenotypic spectrum of
HPE. - Genetic Heterogeneity of Holoprosencephaly Several 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 21q22.3.
HPE2 (157170), caused by mutation in the SIX3 gene (603714), maps to 2p21. HPE3 (142945),
caused by mutation in the Sonic hedgehog gene (SHH; 600725), maps to 7q36. HPE4 (142946),
caused by mutation in the TGIF gene (602630), maps to 18p11.3. HPE5 (609637), caused
by mutation in the ZIC2 gene (603073), maps to 13q32. HPE6 (605934) maps to 2q37.1.
HPE7 (610828), caused by mutation in the PTCH1 gene (601309), maps to 9q22.3. HPE8
(609408) maps to 14q13. HPE9 (610829), caused by mutation in the GLI2 gene (165230),
maps to 2q14. HPE10 (612530) maps to 1q41-q42. HPE11 (614226) is caused by mutation
in the CDON gene (608707) on chromosome 11q23-11q24. For associations pending confirmation,
see MOLECULAR GENETICS. Wallis and Muenke (2000) gave an overview of mutations in
holoprosencephaly. They indicated that at least 12 different loci had been associated
with HPE.;
Inheritance : Autosomal dominant; Isolated cases;
Prefixed ID : %236100;
Origin ID : 236100;
UMLS CUI : C0266667;
Automatic exact mappings (from CISMeF team)
- Currated CISMeF NLP mapping
- DO Cross reference
- HPO term(s)
- ORDO concept(s)
- Semantic type(s)
- UMLS correspondences (same concept)
