European Radiology

, Volume 29, Issue 2, pp 770–782 | Cite as

The spectrum of brainstem malformations associated to mutations of the tubulin genes family: MRI and DTI analysis

  • Filippo Arrigoni
  • Romina Romaniello
  • Denis Peruzzo
  • Andrea Poretti
  • Maria Teresa Bassi
  • Carlo Pierpaoli
  • Enza Maria Valente
  • Sara Nuovo
  • Eugen Boltshauser
  • Thierry André Gerard Marie Huisman
  • Fabio Triulzi
  • Renato Borgatti



To describe the spectrum of brainstem malformations associated to mutations in the tubulin genes taking advantage of magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI).


Fifteen patients (six males; median age, 1.25 years; range, 1 month to 31 years) with mutations in the tubulin genes (TUBA1A = 8, TUBB2B = 4, TUBB3 = 3) studied with MRI and DTI were included in the study. Brain MR exams were reviewed to describe the malformative aspects of the brainstem. Malformations of the supratentorial brain and cerebellum were also recorded. Tractography was performed in seven selected cases.


Fourteen patients (93%) showed complex malformations of the brainstem. Most common findings, apparent on anatomical MR sequences, were brainstem asymmetry (12 cases, 5 of which with a crossed pattern characterised by a hypertrophic right medulla oblongata and hypertrophic left pons), short and small pons on midline (10 cases) and anterior brainstem clefting (6 cases). DTI revealed abnormal transverse pontine fibres (13 cases), fusion of corticospinal tracts and medial lemnisci (9 cases) and a small decussation of the superior cerebellar peduncles (7 cases).


Conventional/anatomical MRI and DTI reveal a complex pattern of brainstem malformations associated with tubulin genes mutations.

Key Points

• Brainstem malformations affect 93% patients with mutated tubulin genes

• MRI shows homolateral and crossed brainstem asymmetries, clefts and pons hypoplasia

• DTI demonstrates irregular representation of transverse pontine fibres and fusion of corticospinal tracts


Nervous system malformations Brain stem Tubulin Diffusion tensor imaging Neurological rehabilitation 



Cortico-spinal tract


Directionally encoded colour


Diencephalic-mesencephalic junction dysplasia


Diffusion tensor imaging


Fractional anisotropy


High angular resolution diffusion imaging


Horizontal gaze palsy and progressive scoliosis


Mean diffusivity


Pontine tegmental cap dysplasia


Transverse pontine fibres



This paper is dedicated to the memory of our dear friend and colleague, Andrea Poretti, an incredibly gifted and talented clinician, scientist and teacher who worked with us on the manuscript before his untimely demise. He will be in our memories forever.

We would like to thank Amritha Nayak for help in preparing Fig. 3.


This study has received funding by the European Research Council (ERC Starting Grant 260888), the Pierfranco and Luisa Mariani Foundation (PADAPORT project) and the Italian Ministry of Health (Ricerca Corrente 2015-2016, Ricerca Finalizzata 2013 NET-2013-02356160, 5X MILLE fundings).

Compliance with ethical standards:


The scientific guarantor of this publication is Dr. Filippo Arrigoni.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

Some study subjects or cohorts have been previously reported in Romaniello R et al. (2017) Tubulin-related cerebellar dysplasia: definition of a distinct pattern of cerebellar malformation. Eur Radiol 27:5080-5092.


• retrospective

• cross-sectional

• multicentre study

Supplementary material

330_2018_5610_MOESM1_ESM.docx (19 kb)
ESM 1 (DOCX 19 kb)


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Copyright information

© European Society of Radiology 2018

Authors and Affiliations

  • Filippo Arrigoni
    • 1
  • Romina Romaniello
    • 2
  • Denis Peruzzo
    • 1
  • Andrea Poretti
    • 3
  • Maria Teresa Bassi
    • 4
  • Carlo Pierpaoli
    • 5
  • Enza Maria Valente
    • 6
    • 7
  • Sara Nuovo
    • 7
    • 8
  • Eugen Boltshauser
    • 9
  • Thierry André Gerard Marie Huisman
    • 3
  • Fabio Triulzi
    • 10
  • Renato Borgatti
    • 2
  1. 1.Neuroimaging LabScientific Institute, IRCCS E. MedeaBosisio PariniItaly
  2. 2.Neuropsychiatry and Neurorehabilitation UnitScientific Institute, IRCCS E. MedeaLeccoItaly
  3. 3.Section of Pediatric Neuroradiology, Division of Pediatric Radiology, Russell H. Morgan Department of Radiology and Radiological ScienceThe Johns Hopkins University School of MedicineBaltimoreUSA
  4. 4.Laboratory of Molecular BiologyScientific Institute, IRCCS E. MedeaLeccoItaly
  5. 5.Quantitative Medical Imaging SectionNational Institute of Biomedical Imaging and Bioengineering, National Institutes of HealthBethesdaUSA
  6. 6.Department of Molecular MedicineUniversity of PaviaPaviaItaly
  7. 7.Neurogenetics Lab, IRCCS Santa Lucia FoundationRomeItaly
  8. 8.Department of Medicine and SurgeryUniversity of SalernoSalernoItaly
  9. 9.Department of Paediatric NeurologyUniversity Children’s HospitalZurichSwitzerland
  10. 10.Neuroradiology DepartmentFondazione IRCCS Ca’ Granda, Ospedale Maggiore PoliclinicoMilanoItaly

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