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Proboscis

MedGen UID:
1684306
Concept ID:
C5194070
Congenital Abnormality
HPO: HP:0012806

Definition

A fleshy, tube-like structure usually located in the midline of the face or just to one side of the midline. [from HPO]

Term Hierarchy

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).
Holoprosencephaly 2
MedGen UID:
322517
Concept ID:
C1834877
Disease or Syndrome
A rare disorder characterized by the partial separation of the cerebral hemispheres. It is associated with mutations in the SIX3 gene.
Holoprosencephaly 3
MedGen UID:
327125
Concept ID:
C1840529
Disease or Syndrome
Any holoprosencephaly in which the cause of the disease is a mutation in the SHH gene.
Cerebrooculonasal syndrome
MedGen UID:
340138
Concept ID:
C1854108
Disease or Syndrome
A multisystem malformation syndrome that has been reported in about 10 patients. The clinical features include bilateral anophthalmia, abnormal nares, central nervous system anomalies, and neurodevelopmental delay. Additional features include brachycephaly and other facial anomalies. Non-facial anomalies have also been reported: postaxial polydactyly, genital hypoplasia. All cases reported so far have been sporadic, suggesting that the syndrome may be due to a new dominant mutation.
Holoprosencephaly 14
MedGen UID:
1811868
Concept ID:
C5676994
Disease or Syndrome
Holoprosencephaly-14 (HPE14) is an autosomal recessive condition characterized by severe developmental delay secondary to brain malformations within the holoprosencephaly spectrum (Drissi et al., 2022). For general phenotypic information and a discussion of genetic heterogeneity of holoprosencephaly, see HPE1 (236100).

Professional guidelines

PubMed

Aliev SA, Zeinalov BM, Aliev ES
Vestn Khir Im I I Grek 2016;175(2):80-6. PMID: 30427154
Smith SL, Lones MA, Bedder M, Alty JE, Cosgrove J, Maguire RJ, Pownall ME, Ivanoiu D, Lyle C, Cording A, Elliott CJ
IET Syst Biol 2015 Dec;9(6):226-33. doi: 10.1049/iet-syb.2015.0030. PMID: 26577157Free PMC Article
Nyberg DA, Mack LA, Bronstein A, Hirsch J, Pagon RA
AJR Am J Roentgenol 1987 Nov;149(5):1051-8. doi: 10.2214/ajr.149.5.1051. PMID: 3314428

Recent clinical studies

Etiology

Acharya SR, Hutapea P
Bioinspir Biomim 2023 Sep 28;18(6) doi: 10.1088/1748-3190/acfb65. PMID: 37726011
El-Dessouky SH, Aboulghar MM, Gaafar HM, Abdella RM, Sharaf MF, Ateya MI, Elarab AE, Zidan WH, Helal RM, Aboelsaud SM, Eid MM, Abdel-Salam GMH
Prenat Diagn 2020 Apr;40(5):565-576. Epub 2020 Feb 10 doi: 10.1002/pd.5649. PMID: 31955448
Galiè M, Clauser LC, Tieghi R, Kawamoto HK, Wolfe SA, Bianchi AE
J Craniomaxillofac Surg 2019 Sep;47(9):1410-1413. Epub 2018 Dec 27 doi: 10.1016/j.jcms.2018.12.013. PMID: 31420283
Tessier P, Ciminello FS, Wolfe SA
Scand J Plast Reconstr Surg Hand Surg 2009;43(4):177-96. doi: 10.1080/02844310802517259. PMID: 19401938
Lelli GJ Jr, Maher EA, Milite JP, Dyleski R
Ophthalmic Plast Reconstr Surg 2008 Nov-Dec;24(6):499-501. doi: 10.1097/IOP.0b013e31818b6e57. PMID: 19033859

Diagnosis

Martin S, Hogan E, Sorenson EP, Cohen-Gadol AA, Tubbs RS, Loukas M
Childs Nerv Syst 2013 Jun;29(6):885-91. Epub 2013 Jan 25 doi: 10.1007/s00381-012-1989-0. PMID: 23354442
Tessier P, Ciminello FS, Wolfe SA
Scand J Plast Reconstr Surg Hand Surg 2009;43(4):177-96. doi: 10.1080/02844310802517259. PMID: 19401938
Lelli GJ Jr, Maher EA, Milite JP, Dyleski R
Ophthalmic Plast Reconstr Surg 2008 Nov-Dec;24(6):499-501. doi: 10.1097/IOP.0b013e31818b6e57. PMID: 19033859
Hwang KS, Ding DC, Chang YK, Chen WH, Chu TY
J Chin Med Assoc 2007 Jul;70(7):298-301. doi: 10.1016/S1726-4901(07)70009-6. PMID: 17631468
Dubourg C, Bendavid C, Pasquier L, Henry C, Odent S, David V
Orphanet J Rare Dis 2007 Feb 2;2:8. doi: 10.1186/1750-1172-2-8. PMID: 17274816Free PMC Article

Therapy

Aliev SA, Zeinalov BM, Aliev ES
Vestn Khir Im I I Grek 2016;175(2):80-6. PMID: 30427154
Smith SL, Lones MA, Bedder M, Alty JE, Cosgrove J, Maguire RJ, Pownall ME, Ivanoiu D, Lyle C, Cording A, Elliott CJ
IET Syst Biol 2015 Dec;9(6):226-33. doi: 10.1049/iet-syb.2015.0030. PMID: 26577157Free PMC Article
Berenji F, Fata A, Hosseininejad Z
Korean J Parasitol 2007 Jun;45(2):145-8. doi: 10.3347/kjp.2007.45.2.145. PMID: 17570979Free PMC Article
Roessler E, Belloni E, Gaudenz K, Jay P, Berta P, Scherer SW, Tsui LC, Muenke M
Nat Genet 1996 Nov;14(3):357-60. doi: 10.1038/ng1196-357. PMID: 8896572
Kink J
J Cell Sci 1976 Jan;20(1):115-33. doi: 10.1242/jcs.20.1.115. PMID: 814127

Prognosis

Tessier P, Ciminello FS, Wolfe SA
Scand J Plast Reconstr Surg Hand Surg 2009;43(4):177-96. doi: 10.1080/02844310802517259. PMID: 19401938
Lelli GJ Jr, Maher EA, Milite JP, Dyleski R
Ophthalmic Plast Reconstr Surg 2008 Nov-Dec;24(6):499-501. doi: 10.1097/IOP.0b013e31818b6e57. PMID: 19033859
Dubourg C, Bendavid C, Pasquier L, Henry C, Odent S, David V
Orphanet J Rare Dis 2007 Feb 2;2:8. doi: 10.1186/1750-1172-2-8. PMID: 17274816Free PMC Article
Worku B
Ethiop Med J 2003 Oct;41(4):367-70. PMID: 15296419
Galguera M, Malave L, Leon A
Gynecol Obstet Invest 1996;42(1):70-2. doi: 10.1159/000291893. PMID: 8840183

Clinical prediction guides

Kaushik S, Kumar R, Kumar S, Sanghi S, Kain P
Sci Prog 2022 Jan-Mar;105(1):368504211067666. doi: 10.1177/00368504211067666. PMID: 34989256Free PMC Article
Weber JS, Ngomtcho SCH, Shaida SS, Chechet GD, Gbem TT, Nok JA, Mamman M, Achukwi DM, Kelm S
Parasit Vectors 2019 Oct 14;12(1):481. doi: 10.1186/s13071-019-3718-y. PMID: 31610794Free PMC Article
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
Dubourg C, Bendavid C, Pasquier L, Henry C, Odent S, David V
Orphanet J Rare Dis 2007 Feb 2;2:8. doi: 10.1186/1750-1172-2-8. PMID: 17274816Free PMC Article
Worku B
Ethiop Med J 2003 Oct;41(4):367-70. PMID: 15296419

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