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Holoprosencephaly 4(HPE4)

MedGen UID:
374488
Concept ID:
C1840528
Disease or Syndrome
Synonym: HPE4
 
Gene (location): TGIF1 (18p11.31)
 
Monarch Initiative: MONDO:0007734
OMIM®: 142946

Definition

A rare disorder caused by mutations in the TGIF gene mapped to chromosome 18p11.3. It is characterized by semilobar holoprosencephaly, hypotelorism, and ptosis. [from NCI]

Clinical features

From HPO
Semilobar holoprosencephaly
MedGen UID:
199694
Concept ID:
C0751617
Congenital Abnormality
A type of holoprosencephaly in which the left and right frontal and parietal lobes are fused and the interhemispheric fissure is only present posteriorly.
Absent nasal septal cartilage
MedGen UID:
867277
Concept ID:
C4021638
Anatomical Abnormality
Lack of the cartilage of the nasal septum.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Median cleft upper lip
MedGen UID:
342454
Concept ID:
C1850256
Congenital Abnormality
A type of cleft lip presenting as a midline (median) gap in the upper lip.
Median cleft palate
MedGen UID:
340670
Concept ID:
C1850968
Congenital Abnormality
Cleft palate of the midline of the palate.
Depressed nasal tip
MedGen UID:
347214
Concept ID:
C1859717
Finding
Decreased distance from the nasal tip to the nasal base.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Hypotelorism
MedGen UID:
96107
Concept ID:
C0424711
Finding
Interpupillary distance less than 2 SD below the mean (alternatively, the appearance of an decreased interpupillary distance or closely spaced eyes).

Professional guidelines

PubMed

Bardi F, Bergman JEH, Siemensma-Mühlenberg N, Elvan-Taşpınar A, de Walle HEK, Bakker MK
Paediatr Perinat Epidemiol 2022 Nov;36(6):804-814. Epub 2022 Jul 12 doi: 10.1111/ppe.12914. PMID: 35821640Free PMC Article
Voutetakis A, Sertedaki A, Dacou-Voutetakis C
Curr Opin Pediatr 2016 Aug;28(4):545-50. doi: 10.1097/MOP.0000000000000378. PMID: 27386973
Bellone S, De Rienzo F, Prodam F, Savastio S, Busti A, Genoni G, Aimaretti G, Bona G
Panminerva Med 2010 Dec;52(4):345-54. PMID: 21183895

Recent clinical studies

Etiology

Fouda MA, Kim TY, Cohen AR
World Neurosurg 2022 Mar;159:48-53. Epub 2021 Dec 22 doi: 10.1016/j.wneu.2021.12.062. PMID: 34954057
Syngelaki A, Hammami A, Bower S, Zidere V, Akolekar R, Nicolaides KH
Ultrasound Obstet Gynecol 2019 Oct;54(4):468-476. doi: 10.1002/uog.20844. PMID: 31408229
Petryk A, Graf D, Marcucio R
Wiley Interdiscip Rev Dev Biol 2015 Jan-Feb;4(1):17-32. Epub 2014 Oct 22 doi: 10.1002/wdev.161. PMID: 25339593Free PMC Article
Turleau C
Orphanet J Rare Dis 2008 Feb 19;3:4. doi: 10.1186/1750-1172-3-4. PMID: 18284672Free PMC Article
Kelberman D, Dattani MT
Pituitary 2007;10(4):393-407. doi: 10.1007/s11102-007-0055-5. PMID: 17587179

Diagnosis

Fouda MA, Kim TY, Cohen AR
World Neurosurg 2022 Mar;159:48-53. Epub 2021 Dec 22 doi: 10.1016/j.wneu.2021.12.062. PMID: 34954057
Syngelaki A, Hammami A, Bower S, Zidere V, Akolekar R, Nicolaides KH
Ultrasound Obstet Gynecol 2019 Oct;54(4):468-476. doi: 10.1002/uog.20844. PMID: 31408229
Toufaily MH, Roberts DJ, Westgate MN, Holmes LB
Am J Clin Pathol 2016 Jan;145(1):86-95. doi: 10.1093/ajcp/aqv012. PMID: 26712875
Volpe P, Campobasso G, De Robertis V, Rembouskos G
Prenat Diagn 2009 Apr;29(4):340-54. doi: 10.1002/pd.2208. PMID: 19184971
Turleau C
Orphanet J Rare Dis 2008 Feb 19;3:4. doi: 10.1186/1750-1172-3-4. PMID: 18284672Free PMC Article

Therapy

Coi A, Santoro M, Pierini A, Rankin J, Glinianaia SV, Tan J, Reid AK, Garne E, Loane M, Given J, Ballardini E, Cavero-Carbonell C, de Walle HEK, Gatt M, García-Villodre L, Gissler M, Jordan S, Kiuru-Kuhlefelt S, Kjaer Urhoj S, Klungsøyr K, Lelong N, Lutke LR, Neville AJ, Rahshenas M, Scanlon I, Wellesley D, Morris JK
Orphanet J Rare Dis 2022 Mar 29;17(1):142. doi: 10.1186/s13023-022-02292-y. PMID: 35351164Free PMC Article
Shannon P
Clin Neuropathol 2020 Nov/Dec;39(6):288-299. doi: 10.5414/NP301266. PMID: 32589127
Guillen-Sacoto MJ, Martinez AF, Abe Y, Kruszka P, Weiss K, Everson JL, Bataller R, Kleiner DE, Ward JM, Sulik KK, Lipinski RJ, Solomon BD, Muenke M
J Hepatol 2017 Oct;67(4):809-817. Epub 2017 Jun 21 doi: 10.1016/j.jhep.2017.06.008. PMID: 28645738Free PMC Article
Cohen MM Jr, Shiota K
Am J Med Genet 2002 Apr 15;109(1):1-15. doi: 10.1002/ajmg.10258. PMID: 11932986
Johnston MC, Bronsky PT
J Craniofac Genet Dev Biol 1991 Oct-Dec;11(4):277-91. PMID: 1812129

Prognosis

Bellone S, De Rienzo F, Prodam F, Savastio S, Busti A, Genoni G, Aimaretti G, Bona G
Panminerva Med 2010 Dec;52(4):345-54. PMID: 21183895
Volpe P, Campobasso G, De Robertis V, Rembouskos G
Prenat Diagn 2009 Apr;29(4):340-54. doi: 10.1002/pd.2208. PMID: 19184971
Turleau C
Orphanet J Rare Dis 2008 Feb 19;3:4. doi: 10.1186/1750-1172-3-4. PMID: 18284672Free PMC Article
Hahn JS, Pinter JD
Semin Pediatr Neurol 2002 Dec;9(4):309-19. doi: 10.1053/spen.2002.32507. PMID: 12523555
Campos P, Cruz G, Lizarraga R, Bancalari E, Guillen D, Castañeda C
Arq Neuropsiquiatr 1994 Dec;52(4):515-22. doi: 10.1590/s0004-282x1994000400010. PMID: 7611945

Clinical prediction guides

Tekendo-Ngongang C, Owosela B, Muenke M, Kruszka P
Am J Med Genet C Semin Med Genet 2020 Mar;184(1):154-158. Epub 2020 Feb 5 doi: 10.1002/ajmg.c.31770. PMID: 32022405
Orioli IM, Castilla EE
Am J Med Genet C Semin Med Genet 2010 Feb 15;154C(1):13-21. doi: 10.1002/ajmg.c.30233. PMID: 20104599
Yamada S
Congenit Anom (Kyoto) 2006 Dec;46(4):164-71. doi: 10.1111/j.1741-4520.2006.00123.x. PMID: 17096815
Carstens MH
J Craniofac Surg 2002 Jan;13(1):129-87; discussion 188-90. doi: 10.1097/00001665-200201000-00032. PMID: 11887012
Osaka K, Tanimura T, Hirayama A, Matsumoto S
J Neurosurg 1978 Nov;49(5):711-24. doi: 10.3171/jns.1978.49.5.0711. PMID: 712393

Recent systematic reviews

Zhang TN, Huang XM, Zhao XY, Wang W, Wen R, Gao SY
PLoS Med 2022 Feb;19(2):e1003900. Epub 2022 Feb 1 doi: 10.1371/journal.pmed.1003900. PMID: 35104296Free PMC Article
Omar AT 2nd, Khu KJO
Childs Nerv Syst 2019 Jul;35(7):1165-1171. Epub 2019 Mar 30 doi: 10.1007/s00381-019-04137-9. PMID: 30929071

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