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
Di Salvo DN
Radiographics 2001 Jul-Aug;21(4):943-55. doi: 10.1148/radiographics.21.4.g01jl14943. PMID: 11452069

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
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
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
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
Turleau C
Orphanet J Rare Dis 2008 Feb 19;3:4. doi: 10.1186/1750-1172-3-4. PMID: 18284672Free PMC Article
Fitz CR
Neuroimaging Clin N Am 1994 May;4(2):263-81. PMID: 8081628

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
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
Caba L, Rusu C, Butnariu L, Panzaru M, Braha E, Volosciuc M, Popescu R, Gramescu M, Bujoran C, Martiniuc V, Covic M, Gorduza EV
Rev Med Chir Soc Med Nat Iasi 2013 Apr-Jun;117(2):321-7. PMID: 24340511
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

Demir M, Sertel E, Ture MZ
Eur J Obstet Gynecol Reprod Biol 2021 May;260:64-69. Epub 2021 Mar 15 doi: 10.1016/j.ejogrb.2021.03.016. PMID: 33743359
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
Syngelaki A, Guerra L, Ceccacci I, Efeturk T, Nicolaides KH
Ultrasound Obstet Gynecol 2017 Jul;50(1):45-48. Epub 2017 Apr 23 doi: 10.1002/uog.17286. PMID: 27558969
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
Turleau C
Orphanet J Rare Dis 2008 Feb 19;3:4. doi: 10.1186/1750-1172-3-4. PMID: 18284672Free PMC Article

Clinical prediction guides

Fujino S, Enokizono M, Ihara S, Kono T, Miyama S
BMC Neurol 2022 Aug 25;22(1):316. doi: 10.1186/s12883-022-02764-5. PMID: 36008788Free PMC Article
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
Yamada S
Congenit Anom (Kyoto) 2006 Dec;46(4):164-71. doi: 10.1111/j.1741-4520.2006.00123.x. PMID: 17096815
Bennett JL
J Neuroophthalmol 2002 Dec;22(4):286-96. doi: 10.1097/00041327-200212000-00006. PMID: 12464733
Carstens MH
J Craniofac Surg 2002 Jan;13(1):129-87; discussion 188-90. doi: 10.1097/00001665-200201000-00032. PMID: 11887012

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...