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Ethmocephaly

MedGen UID:
452352
Concept ID:
C0266680
Congenital Abnormality
Synonym: Ethmocephalus
SNOMED CT: Ethmocephalus (55709000); Ethmocephaly (55709000)
 
HPO: HP:0030779

Definition

Ethmocephaly is the rarest form of holoprosencephaly, which occurs due to an incomplete cleavage of the forebrain. Clinically, the disease presents with a proboscis, hypotelorism, microphthalmos and malformed ears. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVEthmocephaly

Conditions with this feature

Holoprosencephaly 1
MedGen UID:
78617
Concept ID:
C0266667
Congenital Abnormality
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. See also HPE2 (157170), caused by mutation in the SIX3 gene (603714) on 2p21; HPE3 (142945), caused by mutation in the SHH gene (600725) on 7q36; HPE4 (142946), caused by mutation in the TGIF gene (602630) on 18p11; HPE5 (609637), caused by mutation in the ZIC2 gene (603073) on 13q32; HPE6 (605934), mapped to 2q37; HPE7 (610828), caused by mutation in the PTCH1 gene (601309) on 9q22; HPE8 (609408), mapped to 14q13; HPE9 (610829), caused by mutation in the GLI2 gene (165230) on 2q14; HPE10 (612530), mapped to 1q41-q42; HPE11 (614226), caused by mutation in the CDON gene (608707) on 11q24; HPE12 (618500), caused by mutation in the CNOT1 gene (604917) on 16q21; HPE13 (301043), caused by mutation in the STAG2 gene (300826) on Xq25; and HPE14 (619895), caused by mutation in the PLCH1 gene (612835) on 3q25. Wallis and Muenke (2000) gave an overview of mutations in holoprosencephaly. They indicated that at least 12 different loci had been associated with HPE. Mutations in genes involved in the multiprotein cohesin complex, including STAG2, have been shown to be involved in midline brain defects such as HPE. Mutations in some of those genes cause Cornelia de Lange syndrome (CDLS; see 122470), and some patients with severe forms of CDLS may have midline brain defects. See, for example, CDLS2 (300590), CDLS3 (610759), and CDLS4 (614701).

Recent clinical studies

Etiology

Orioli IM, Castilla EE
Am J Med Genet A 2007 Dec 15;143A(24):3088-99. doi: 10.1002/ajmg.a.32104. PMID: 17987642
McGahan JP, Nyberg DA, Mack LA
AJR Am J Roentgenol 1990 Jan;154(1):143-8. doi: 10.2214/ajr.154.1.2104699. PMID: 2104699
Cohen MM Jr
Teratology 1989 Sep;40(3):211-35. doi: 10.1002/tera.1420400304. PMID: 2688166

Diagnosis

Ionescu CA, Calin D, Navolan D, Matei A, Dimitriu M, Herghelegiu C, Ples L
Medicine (Baltimore) 2018 Jul;97(29):e11521. doi: 10.1097/MD.0000000000011521. PMID: 30024536Free PMC Article
Das G, Gayen S, Bandyopadhyay S, Das D
Middle East Afr J Ophthalmol 2012 Oct;19(4):429-31. doi: 10.4103/0974-9233.102769. PMID: 23248551Free PMC Article
Kitova TT, Aida M, Dorra Z, Dalenda C, Gaigi SS
Folia Med (Plovdiv) 2011 Jul-Sep;53(3):39-44. doi: 10.2478/v10153-011-0055-0. PMID: 22359981
Orioli IM, Castilla EE
Am J Med Genet A 2007 Dec 15;143A(24):3088-99. doi: 10.1002/ajmg.a.32104. PMID: 17987642
Goldstein I, Weissman A, Brill-Zamir R, Laevsky I, Drugan A
Prenat Diagn 2003 Oct;23(10):788-90. doi: 10.1002/pd.689. PMID: 14558020

Prognosis

Das G, Gayen S, Bandyopadhyay S, Das D
Middle East Afr J Ophthalmol 2012 Oct;19(4):429-31. doi: 10.4103/0974-9233.102769. PMID: 23248551Free PMC Article

Clinical prediction guides

Ionescu CA, Calin D, Navolan D, Matei A, Dimitriu M, Herghelegiu C, Ples L
Medicine (Baltimore) 2018 Jul;97(29):e11521. doi: 10.1097/MD.0000000000011521. PMID: 30024536Free PMC Article
Yamada S
Congenit Anom (Kyoto) 2006 Dec;46(4):164-71. doi: 10.1111/j.1741-4520.2006.00123.x. PMID: 17096815

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