Skip to main content
SpringerLink
Log in

Holoprosencephaly

  • Reference work entry
  • First Online:
Atlas of Genetic Diagnosis and Counseling

  • 198 Accesses

Abstract

Holoprosencephaly (HPE) is a heterogeneous entity of CNS anomalies caused by the impaired midline cleavage of the embryonic forebrain. The incidence is estimated to be 1 in 16,000 live births and observed in 1 of 250 spontaneous abortions (Roessler and Muenke 2001).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Araúz, R. F., Solomon, B. D., Pineda-Alvarez, D. E., et al. (2010). A hypomorphic allele in the FGF8 gene contributes to holoprosencephaly and is allelic to gonadotropin-releasing hormone deficiency in humans. Molecular Syndromology, 1(2), 59–66.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bae, G. U., Domené, S., Roessler, E., et al. (2011). Mutations in CDON, encoding a hedgehog receptor, result in holoprosencephaly and defective interactions with other hedgehog receptors. American Journal of Human Genetics, 89, 231–240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bangma, M., Lunshof, S., van Opstal, D., et al. (2011). Prenatal diagnosis of alobar holoprosencephaly, cyclopia, proboscis and isochromosome 18q in the second trimester. American Journal of Perinatology Reports, 1, 73–76.

    Article  PubMed  PubMed Central  Google Scholar 

  • Barkovich, A. J., & Quint, D. J. (1993). Middle interhemispheric fusion: Anunusual variant of holoprosencephaly. AJNR. American Journal of Neuroradiology, 14, 431–440.

    CAS  PubMed  Google Scholar 

  • Barr, M., & Cohen, M. M., Jr. (1999). Holoprosencephaly survival and performance. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics, 89, 116–120.

    Article  Google Scholar 

  • Bendavid, C., Rochard, L., Dubourg, C., et al. (2009). Array-CGH analysis indicates a high prevalence of genomic rearrangements in holoprosencephaly: An updated map of candidate loci. Human Mutation, 30, 1175–1182.

    Article  CAS  PubMed  Google Scholar 

  • Bendavid, C., Dupé, V., Rochard, L., et al. (2010). Holoprosencephaly an update on cytogenetic abnormalities. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics, 154C, 86–92.

    Article  PubMed  Google Scholar 

  • Berry, S. A., Pierpont, M. E., & Gorlin, R. J. (1984). Single central incisor in familial holoprosencephaly. Journal of Pediatrics, 104, 877–880.

    Article  CAS  PubMed  Google Scholar 

  • Berry, S. M., Gosden, C., Snijders, R. J., et al. (1990). Fetal holoprosencephaly: Associated malformations and chromosomal defects. Fetal Diagnosis and Therapy, 5, 92–99.

    Article  CAS  PubMed  Google Scholar 

  • Bertolacini, C. D. P., Richieri-Costa, A., & Ribeiro-Bicudo, L. A. (2010). Sonic hedgehog (SHH) mutation in patients within the spectrum of holoprosencephaly. Brain & Development, 32, 217–222.

    Article  Google Scholar 

  • Blass, H.-G. K., Eik-Nes, S. H., Vainio, T., et al. (2000). Alobar holoprosencephaly at 9 weeks gestational age visualized by two- and three-dimensional ultrasound. Ultrasound in Obstetrics & Gynecology, 15, 62–65.

    Article  Google Scholar 

  • Blaas, H.-G. K., Eriksson, A. G., Salvesen, K. Å., et al. (2002). Brain and faces in holoprosencephaly: Pre- and postnatal description of 30 cases. Ultrasound in Obstetrics & Gynecology, 19, 24–38.

    Article  CAS  Google Scholar 

  • Brown, S. A., Warburton, D., Brown, L. Y., et al. (1998). Holoprosencephaly due to mutations in ZIC2, a homologue of Drosophila odd-paired. Nature Genetics, 20, 180–183.

    Article  CAS  PubMed  Google Scholar 

  • Chen, H., Rightmire, D., Zapata, C., et al. (1992). Frontonasal dysplasia and arhinencephaly resulting from unbalanced segregation of a maternal t(2;7)(q31;q36). Dysmorphology and Clinical Genetics, 6, 99–106.

    Google Scholar 

  • Chen, C.-P., Liu, F.-F., Jan, S.-W., et al. (1996). Prenatal diagnosis of terminal deletion 7q and partial trisomy 3p in fetuses with holoprosencephaly. Clinical Genetics, 50, 321–326.

    Article  CAS  PubMed  Google Scholar 

  • Chen, C.-P., Devriendt, K., Lee, C.-C., et al. (1999). Prenatal diagnosis of partial trisomy 3p(3p23 → pter) and monosomy 7q(7q36 → qter) in a fetus with microcephaly, alobar holoprosencephaly and cyclopia. Prenatal Diagnosis, 19, 986–989.

    Article  CAS  PubMed  Google Scholar 

  • Chen, C.-P., Chern, S.-R., Wang, W., et al. (2001). Prenatal diagnosis of partial monosomy 18p(18p11.2 → pter) and trisomy 21q(q22.3 → qter) with alobar holoprosencephaly and premaxillary agenesis. Prenatal Diagnosis, 21, 346–350.

    Article  CAS  PubMed  Google Scholar 

  • Chen, C.-P., Chern, S.-R., Du, S.-H., et al. (2002). Molecular diagnosis of a novel heterozygous 268 C → T (R90C) mutation in TGIF gene in a fetus with holoprosencephaly and premaxillary agenesis. Prenatal Diagnosis, 22, 5–7.

    Article  CAS  PubMed  Google Scholar 

  • Cohen, M. M., Jr. (1982). An update on the holoprosencephalic disorders. Journal of Pediatrics, 101, 865–869.

    Article  PubMed  Google Scholar 

  • Cohen, M. M., Jr. (1989a). Perspectives on holoprosencephaly: Part I. Epidemiology, genetics and syndromology. Teratology, 40, 211–235.

    Article  PubMed  Google Scholar 

  • Cohen, M. M., Jr. (1989b). Perspectives on holoprosencephaly. Part III. Spectra, distinctions, continuities, and discontinuities. American Journal of Medical Genetics, 34, 271–288.

    Article  PubMed  Google Scholar 

  • Cohen, M. M., Jr. (2006). Holoprosencephaly: Clinical, anatomical, and molecular dimensions. Birth Defects Research (Part A), 76, 658–673.

    Article  CAS  Google Scholar 

  • Cohen, M. M., Jr., & Shiota, K. (2002). Teratogenesis of holoprosencephaly. American Journal of Medical Genetics, 109, 1–15.

    Article  PubMed  Google Scholar 

  • Cohen, M. M., & Sulik, K. (1992). Perspectives on holoprosencephaly: Part II. Central nervous system, craniofacial anatomy, syndrome commentary, diagnostic approach, and experimental studies. Journal of Craniofacial Genetics and Developmental Biology, 12, 196–244.

    PubMed  Google Scholar 

  • de la Cruz, J. M., Bamford, R. N., Burdine, R. D., et al. (2002). A loss-of-function mutation in the CFC domain of TDGF1 is associated with human forebrain defects. Human Genetics, 110, 422–428.

    Article  PubMed  Google Scholar 

  • Delezoide, A. L., Narcy, F., & Larroche, J. C. (1990). Cerebral midline developmental anomalies: Spectrum and associated features. Genetic Counseling, 1, 197–210.

    CAS  PubMed  Google Scholar 

  • DeMyer, W., & Zeman, W. (1963). Alobar holoprosencephaly (arhinencephaly) with median cleft lip and palate. Clinical nosologic and electroencephalographic considerations. Confinia Neurologica, 23, 1–36.

    Article  CAS  PubMed  Google Scholar 

  • DeMyer, W., Zeman, W., & Palmer, C. G. (1964). The face predicts the brain. Diagnostic significance of median facial anomalies for holoprosencephaly arhinencephaly. Pediatrics, 43, 256–263.

    Google Scholar 

  • Dubourg, C., Lazaro, L., Pasquier, L., et al. (2004). Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: Mutation review and genotype/phenotype correlations. Human Mutation, 241, 43–51.

    Article  Google Scholar 

  • Dubourg, C., Bendavid, C., Pasquier, L., et al. (2007). Holoprosencephaly. Orphanet Journal of Rare Diseases, 2, 8–21.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dupé, V., Rochard, L., Mercier, S., et al. (2011). NOTCH, a new signaling pathway implicated in holoprosencephaly. Human Molecular Genetics, 20, 1122–1131.

    Article  PubMed  Google Scholar 

  • Ebina, Y., Yamada, H., Kato, E. H., et al. (2001). Prenatal diagnosis of agnathia-holoprosencephaly: Three-dimensional imaging by helical computed tomography. Prenatal Diagnosis, 21, 68–71.

    Article  CAS  PubMed  Google Scholar 

  • Frints, S. G. M., Schoenmakers, E. F. P. M., Smeets, E., et al. (1998). De novo 7q36 deletions: Breakpoint analysis and types of holoprosencephaly. American Journal of Medical Genetics, 75, 153–158.

    Article  CAS  PubMed  Google Scholar 

  • Gripp, K. W., Edwards, M. C., Mowat, D., et al. (1998). Mutations in the transcription factor TGIF in holoprosencephaly. American Journal of Human Genetics, 63, A32.

    Google Scholar 

  • Gripp, K. W., Wotton, D., Edwards, M. C., et al. (2000). Mutations in TGIF cause holoprosencephaly and link NODAL signalling to human neural axis determination. Nature Genetics, 25, 205–208.

    Article  CAS  PubMed  Google Scholar 

  • Gurrieri, F., Trask, B. J., van den Engh, G., et al. (1993). Physical mapping of holoprosencephaly critical region of chromosome 7q36. Nature Genetics, 3, 247–251.

    Article  CAS  PubMed  Google Scholar 

  • Hahn, J. S., & Barnes, P. D. (2010). Neuroimaging advances in holoprosencephaly: Refining the spectrum of the midline malformation. American Journal of Medical Genetics. Part C, 154C, 120–132.

    Article  Google Scholar 

  • Hahn, J. S., & Plawner, L. L. (2004). Evaluation and management of children with holoprosencephaly. Pediatric Neurology, 31, 79–88.

    Article  PubMed  Google Scholar 

  • Hahn, J. S., Barnes, P. D., Clegg, N. J., et al. (2010). Septopreoptic holoprosencephaly: A mild subtype associated with midline craniofacial anomalies. AJNR. American Journal of Neuroradiology, 31, 1596–1601.

    Article  CAS  PubMed  Google Scholar 

  • Johnson, C. Y., & Rasmussen, S. A. (2010). Non-genetic risk factors for holoprosencephaly. American Journal of Medical Genetics. Part C, 154C, 73–85.

    Article  Google Scholar 

  • Kauvar, E. F., Solomon, B. D., Curry, C. J. R., et al. (2010). Holoprosencephaly and agnathia spectrum: Presentation of two new patients and review of the literature. American Journal of Medical Genetics. Part C, 154C, 158–169.

    Article  Google Scholar 

  • Lai, T.-H., Chang, C.-H., Yu, C.-H., et al. (2000). Prenatal diagnosis of alobar holoprosencephaly by two-dimensional and three-dimensional ultrasound. Prenatal Diagnosis, 20, 400–403.

    Article  CAS  PubMed  Google Scholar 

  • Levy, E. B., Stashinko, E., Clegg, N. J., et al. (2010). Management of children with holoprosencephaly. American Journal of Medical Genetics. Part C, 154C, 183–190.

    Article  Google Scholar 

  • Mercier, S., Dubourg, C., Belleguic, M., et al. (2010). Genetic counseling and “molecular” prenatal diagnosis of holoprosencephaly (HPE). American Journal of Medical Genetics. Part C, 154C, 191–196.

    Article  Google Scholar 

  • Mouden, C., de Tayrac, M., & Dubourg, C. (2015). Homozygous STIL mutation causes holoprosencephaly and microcephaly in two siblings. PloS One, 10, e1–e11.

    Article  Google Scholar 

  • Muenke, M. (1989). Clinical, cytogenetic and molecular approaches to the genetic heterogeneity of holoprosencephaly. American Journal of Medical Genetics, 34, 237–245.

    Article  Google Scholar 

  • Muenke, M., & Beachy, P. A. (2000). Genetics of ventral forebrain development and holoprosencephaly. Current Opinion in Genetics and Development, 10, 262–269.

    Article  CAS  PubMed  Google Scholar 

  • Muenke, M., & Cohen, M. M., Jr. (2000). Genetic approaches to understanding brain development: Holoprosencephaly as a model. Mental Retardation and Developmental Disabilities Research Reviews, 6, 15–21.

    Article  CAS  PubMed  Google Scholar 

  • Nanni, L., Roen, L. A., Lammer, E. J., et al. (2000). Holoprosencephaly: Molecular study of a California population. American Journal of Medical Genetics, 90, 315–319.

    Article  CAS  PubMed  Google Scholar 

  • Nyberg, D. A., Mack, L. A., Bronstein, A., et al. (1987). Holoprosencephaly: Prenatal sonographic diagnosis. American Journal of Roentgenology, 149, 1051–1058.

    Article  CAS  PubMed  Google Scholar 

  • Ouspenskaia, M. V., Karkera, J. D., Roessler, E., et al. (2002). Role of FAST1 gene in the development of holoprosencephaly (HPE) and congenital cardiac malformations in humans. In American Society of Human Genetics, 52nd annual meeting (p. 313), Baltimore. Abstract 822, 15–19 Oct 2002.

    Google Scholar 

  • Pasquier, L., Dubourg, C., Gonzales, M., et al. (2005). First occurrence of aprosencephaly/atelencephaly and holoprosencephaly in a family with a SIX3 gene mutation and phenotype/genotype correlation in our series of SIX3 mutations. Journal of Medical Genetics, 42, e4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pilu, G., Sandri, F., Perolo, A., et al. (1992). Prenatal diagnosis of lobar holoprosencephaly. Ultrasound in Obstetrics & Gynecology, 2, 88–92.

    Article  CAS  Google Scholar 

  • Pineda-Alvarez, D. E., Dubourg, C., David, V., et al. (2010). Current recommendations for the molecular evaluation of nearly diagnosed holoprosencephaly patients. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics, 154C, 93–101.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pineda-Alvarez, D. E., Roessler, E., Hu, P., et al. (2012). Missense substitutions in the GAS1 protein present in holoprosencephaly patients reduce the affinity for its ligand, SHH. Human Genetics, 131, 301–310.

    Article  CAS  PubMed  Google Scholar 

  • Rahimov, F., Ribeiro, L. A., de Miranda, E., et al. (2006). GLI2 mutations in four Brazilian patients: How wide is the phenotypic spectrum? American Journal of Medical Genetics. Part A, 140, 2571–2576.

    Article  PubMed  Google Scholar 

  • Ribeiro, L. A., Quiezi, R. G., Nascimento, A., et al. (2010). Holoprosencephaly and holoprosencephaly-like phenotype and GAS1 DNA sequence changes: Report of four Brazilian patients. American Journal of Medical Genetics A, 152A, 1688–1694.

    Article  CAS  Google Scholar 

  • Roessler, E., & Muenke, M. (2001). Midline and laterality defects: Left and right meet in the middle. BioEssays, 23, 888–900.

    Article  CAS  PubMed  Google Scholar 

  • Roessler, E., Belloni, E., Gaudenz, K., et al. (1996). Mutations in the human sonic hedgehog gene cause holoprosencephaly. Nature Genetics, 14, 357–360.

    Article  CAS  PubMed  Google Scholar 

  • Roessler, E., Ouspenskaia, M. V., Karkera, J. D., et al. (2008). Reduced NODAL signaling strength via mutation of several pathway members including FOXH1 is linked to human heart defects and holoprosencephaly. American Journal of Human Genetics, 83, 18–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roessler, E., Ma, Y., Ouspenskaia, M. V., Lacbawan, F., et al. (2009). Truncating loss-of-function mutations of DISP1 contribute to holoprosencephaly-like microform features in humans. Human Genetics, 125, 393–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simon, E. M., Hevner, R. F., Pinter, J. D., et al. (2002). The middle interhemispheric variant of holoprosencephaly. AJNR. American Journal of Neuroradiology, 23, 151–155.

    PubMed  Google Scholar 

  • Solomon, B. D., Gropman, A., & Muenke, M. (2013). Holoprosencephaly overview. GeneReviews. Updated 29 Aug 2013. http://www.ncbi.nlm.nih.gov/books/NBK1530

  • Srivastava, K., Solomon, B. D., Ming, J. E., et al. (2012). Molecular analysis of the Noggin (NOG) gene in holoprosencephaly patients. Molecular Genetics and Metabolism, 106, 241–243.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vance, G. H., Nickerson, C., Sarnat, L., et al. (1998). Molecular cytogenetic analysis of patients with holoprosencephaly and structural rearrangements of 7q. American Journal of Medical Genetics, 76, 51–57.

    Article  CAS  PubMed  Google Scholar 

  • Verlinsky, Y., Rechitsky, S., Verlinsky, O., et al. (2003). Preimplantation diagnosis for sonic hedgehog mutation causing familial holoprosencephaly. The New England Journal of Medicine, 348, 1449–1454.

    Article  CAS  PubMed  Google Scholar 

  • Wallis, D. E., & Muenke, M. (1999). Molecular mechanisms of holoprosencephaly. Molecular Genetics and Metabolism, 68, 126–138.

    Article  CAS  PubMed  Google Scholar 

  • Wallis, D. E., & Muenke, M. (2000). Mutations in holoprosencephaly. Human Mutation, 16, 99–108.

    Article  CAS  PubMed  Google Scholar 

  • Wallis, D. E., Roessler, E., Hehr, U., et al. (1999). Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly. Nature Genetics, 22, 196–198.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Genetics, Shriners Hospitals for Children, Perinatal and Clinical Genetics, Department of Pediatrics, LSU Health Sciences Center, Shreveport, LA, USA

    Harold Chen

Authors
  1. Harold Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media LLC

About this entry

Cite this entry

Chen, H. (2017). Holoprosencephaly. In: Atlas of Genetic Diagnosis and Counseling. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2401-1_119

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2401-1_119

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-2400-4

  • Online ISBN: 978-1-4939-2401-1

  • eBook Packages: MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation