, Volume 61, Issue 8, pp 949–952 | Cite as

Hypothalamic malformations in patients with X-linked deafness and incomplete partition type 3

  • Ata Siddiqui
  • Alessandra D’Amico
  • Giovanna Stefania Colafati
  • Domenico Cicala
  • Giacomo Talenti
  • Kaukab Rajput
  • Lorenzo Pinelli
  • Felice D’ArcoEmail author
Short Report


Patients with X-linked deafness carry mutations in the POU3F4 gene and have pathognomonic inner ear malformations characterised by symmetrical incomplete partition type 3 (absent modiolus and lamina spiralis but preserved interscalar septum in a normal-sized cochlea) and large internal auditory meatus (IAM) with an increased risk of gusher during stapes surgery. We describe a range of fairly characteristic malformations in the hypothalamus of some patients with this rare condition, ranging from subtle asymmetric appearance and thickening of the tuber cinereum to more marked hypothalamic enlargement. We discuss the role of POU3F4 in the normal development of both the inner ear and hypothalamus and the proposed pathophysiology of incomplete partition type 3.


X-linked deafness Hypothalamic hamartoma Magnetic resonance imaging Gusher Incomplete partition 



No funding was received for this study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional research committee (Clinical Research Adoption Committee) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study or legal authorized representatives (LAR).

Supplementary material

234_2019_2230_Fig3_ESM.png (2.3 mb)

(PNG 2399 kb)

234_2019_2230_MOESM1_ESM.tif (916 kb)
High resolution image (TIF 915 kb)


  1. 1.
    Bitner-Glindzicz M, Turnpenny P, Höglund P, Kääriäinen H, Sankila EM, van der Maarel SM, de Kok YJM, Ropers HH, Cremers FPM, Pembrey M, Malcolm S (1995) Further mutations in brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3. Hum Mol Genet 4:1467–1469CrossRefPubMedGoogle Scholar
  2. 2.
    Talenti G, Manara R, Brotto D, D’Arco F (2018) High-resolution 3 T magnetic resonance findings in cochlear hypoplasias and incomplete partition anomalies: a pictorial essay. Br J Radiol 91:20180120CrossRefPubMedGoogle Scholar
  3. 3.
    Andersen B, Rosenfeld MG (2001) POU domain factors in the neuroendocrine system: lessons from developmental biology provide insights into human disease. Endocr Rev 22:2–35. PubMedGoogle Scholar
  4. 4.
    Sennaroglu L (2016) Histopathology of inner ear malformations: do we have enough evidence to explain pathophysiology? Cochlear Implants Int 17:3–20CrossRefPubMedGoogle Scholar
  5. 5.
    Valdueza JM, Cristante L, Dammann O et al (1994) Hypothalamic hamartomas: with special reference to gelastic epilepsy and surgery. Neurosurgery 34(6):949–958PubMedGoogle Scholar
  6. 6.
    Bach I, Robinson D, Thomas N, Ropers HH, Cremers FP (1992) Physical fine mapping of genes underlying X-linked deafness and non fra (X)-X-linked mental retardation at Xq21. Hum Genet 89:620–624CrossRefPubMedGoogle Scholar
  7. 7.
    Olson NR, Lehman RH (1968) Cerebrospinal fluid otorrhea and the congenitally fixed stapes. Laryngoscope 78:352–360CrossRefPubMedGoogle Scholar
  8. 8.
    D’Arco F, Talenti G, Lakshmanan R, Stephenson K, Siddiqui A, Carney O (2017) Do measurements of inner ear structures help in the diagnosis of inner ear malformations? A review of literature. Otol Neurotol 38:e384–e392CrossRefPubMedGoogle Scholar
  9. 9.
    Whitehead MT, Vezina G (2014) Interhypothalamic adhesion: a series of 13 cases. AJNR Am J Neuroradiol 35(10):2002–2006CrossRefPubMedGoogle Scholar
  10. 10.
    Avula S, Alam N, Roberts E (2012) Cochlear abnormality in a case of Pallister-Hall syndrome. Pediatr Radiol 42:1502–1505CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NeuroradiologyKing’s College HospitalLondonUK
  2. 2.Department of Advanced Biomedical SciencesUniversity of Naples “Federico II”NaplesItaly
  3. 3.Oncological Neuroradiology Unit, Department of ImagingIRCCS Bambino Gesù Children’s HospitalRomeItaly
  4. 4.Neuroradiology UnitSantobono-Pausilipon Children’s HospitalNaplesItaly
  5. 5.Neuroradiology UnitVerona University HospitalVeronaItaly
  6. 6.Cochlear Implant DepartmentGreat Ormond Street HospitalLondonUK
  7. 7.Neuroradiology UnitPediatric Neuroradiology Section, ASST Spedali CiviliBresciaItaly
  8. 8.Radiology DepartmentGreat Ormond Street HospitalLondonUK

Personalised recommendations