U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Lobar holoprosencephaly
MedGen UID:
96559
Concept ID:
C0431362
Congenital Abnormality
A type of holoprosencephaly in which most of the right and left cerebral hemispheres and lateral ventricles are separated but the most rostral aspect of the telencephalon, the frontal lobes, are fused, especially ventrally.
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.
Aplasia of the olfactory tract
MedGen UID:
1696405
Concept ID:
C5209227
Congenital Abnormality
Aplasia (congenital absence) of the olfactory tract, which causes anosmia, a complete loss of the sense of smell.
Absent nasal septal cartilage
MedGen UID:
867277
Concept ID:
C4021638
Anatomical Abnormality
Lack of the cartilage of the nasal septum.
Aplasia of the premaxilla
MedGen UID:
869286
Concept ID:
C4023712
Finding
Absence of the premaxilla, which is the embryonic structure that forms the anterior part of the maxilla.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
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.
Diabetes insipidus
MedGen UID:
8349
Concept ID:
C0011848
Disease or Syndrome
A state of excessive water intake and hypotonic (dilute) polyuria. Diabetes insipidus may be due to failure of vasopressin (AVP) release (central or neurogenic diabetes insipidus) or to a failure of the kidney to respond to AVP (nephrogenic diabetes insipidus).
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

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
Chen CP
Ultrasound Obstet Gynecol 2002 Apr;19(4):421-2. doi: 10.1046/j.1469-0705.2002.00533_5.x. PMID: 11952980

Recent clinical studies

Etiology

O'Neil LM, Pollaers K, Sale P, Vijayasekaran S, Herbert H
Int J Pediatr Otorhinolaryngol 2023 Aug;171:111654. Epub 2023 Jul 11 doi: 10.1016/j.ijporl.2023.111654. PMID: 37467582
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
Rodriguez N, Casasbuenas A, Andreeva E, Odegova N, Wong AE, Sepulveda W
J Ultrasound Med 2019 Mar;38(3):805-809. Epub 2018 Aug 31 doi: 10.1002/jum.14759. PMID: 30171631
Pourebrahim R, Houtmeyers R, Ghogomu S, Janssens S, Thelie A, Tran HT, Langenberg T, Vleminckx K, Bellefroid E, Cassiman JJ, Tejpar S
J Biol Chem 2011 Oct 28;286(43):37732-40. Epub 2011 Sep 9 doi: 10.1074/jbc.M111.242826. PMID: 21908606Free PMC Article
Turleau C
Orphanet J Rare Dis 2008 Feb 19;3:4. doi: 10.1186/1750-1172-3-4. PMID: 18284672Free PMC Article

Diagnosis

Brauner R, Bignon-Topalovic J, Bashamboo A, McElreavey K
PLoS One 2023;18(12):e0292664. Epub 2023 Dec 14 doi: 10.1371/journal.pone.0292664. PMID: 38096238Free PMC Article
Rodriguez N, Casasbuenas A, Andreeva E, Odegova N, Wong AE, Sepulveda W
J Ultrasound Med 2019 Mar;38(3):805-809. Epub 2018 Aug 31 doi: 10.1002/jum.14759. PMID: 30171631
Blaas HG, Eik-Nes SH
Prenat Diagn 2009 Apr;29(4):312-25. doi: 10.1002/pd.2170. PMID: 19194866
Sanlaville D, Verloes A
Eur J Hum Genet 2007 Apr;15(4):389-99. Epub 2007 Feb 14 doi: 10.1038/sj.ejhg.5201778. PMID: 17299439
Coll Masfarré S, Majós Torró C, Aguilera Grijalvo C, Pons Irazazábal LC
Eur Radiol 1998;8(4):631-3. doi: 10.1007/s003300050450. PMID: 9569338

Therapy

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
Eleftheriou G, Butera R, Manzo L
Clin Exp Obstet Gynecol 2012;39(4):535-6. PMID: 23444763
Cohen MM Jr, Shiota K
Am J Med Genet 2002 Apr 15;109(1):1-15. doi: 10.1002/ajmg.10258. PMID: 11932986
De Wals P, Bloch D, Calabro A, Calzolari E, Cornel MC, Johnson Z, Ligutic I, Nevin N, Pexieder I, Stoll C
Paediatr Perinat Epidemiol 1991 Oct;5(4):445-7. doi: 10.1111/j.1365-3016.1991.tb00730.x. PMID: 1754503
Ohtsuka Y, Matsuda M, Ogino T, Kobayashi K, Ohtahara S
Brain Dev 1987;9(4):418-21. doi: 10.1016/s0387-7604(87)80116-x. PMID: 3434717

Prognosis

Karl K, Kainer F, Heling KS, Chaoui R
Ultraschall Med 2011 Aug;32(4):342-61. Epub 2011 Aug 1 doi: 10.1055/s-0031-1273463. PMID: 21809236
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
Fadel HE
J Child Neurol 1989;4 Suppl:S107-12. doi: 10.1177/0883073889004001s16. PMID: 2681372
Byrd SE
J Natl Med Assoc 1989 Aug;81(8):873-81. PMID: 2671396Free PMC Article

Clinical prediction guides

Brauner R, Bignon-Topalovic J, Bashamboo A, McElreavey K
PLoS One 2023;18(12):e0292664. Epub 2023 Dec 14 doi: 10.1371/journal.pone.0292664. PMID: 38096238Free PMC Article
Laure-Kamionowska M, Szymanska K, Klepacka T
Folia Neuropathol 2015;53(4):387-94. doi: 10.5114/fn.2015.56553. PMID: 26785373
Savastano CP, Bernardi P, Seuánez HN, Moreira MÂ, Orioli IM
Birth Defects Res A Clin Mol Teratol 2014 Apr;100(4):300-6. Epub 2014 Feb 12 doi: 10.1002/bdra.23216. PMID: 24677696
Ming JE, Kaupas ME, Roessler E, Brunner HG, Golabi M, Tekin M, Stratton RF, Sujansky E, Bale SJ, Muenke M
Hum Genet 2002 Apr;110(4):297-301. Epub 2002 Mar 2 doi: 10.1007/s00439-002-0695-5. PMID: 11941477
Sarnat HB
J Pediatr 1978 Apr;92(4):624-6. doi: 10.1016/s0022-3476(78)80307-2. PMID: 633025

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

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...