University of Oulu

Gorcenco, S., Komulainen-Ebrahim, J., Nordborg, K., Suo-Palosaari, M., Andréasson, S., Krüger, J., Nilsson, C., Kjellström, U., Rahikkala, E., Turkiewicz, D., Karlberg, M., Nilsson, L., Cammenga, J., Tedgård, U., Davidsson, J., Uusimaa, J., Puschmann, A. (2017) Ataxia-pancytopenia syndrome with SAMD9L mutations. Neurology Genetics, 3 (5), e183. doi:10.1212/NXG.0000000000000183

Ataxia-pancytopenia syndrome with SAMD9L mutations

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Author: Gorcenco, Sorina1; Komulainen- Ebrahim, Jonna2,3,4,5; Nordborg, Karin6;
Organizations: 1Section of Neurology, Department of Clinical Sciences, Skåne University Hospital, Lund University
2Department of Children and Adolescents, Oulu University Hospital
3PEDEGO Research Unit, University of Oulu
4Medical Research Center Oulu, University of Oulu
5Biocenter Oulu, University of Oulu
6Section of Pediatric Neurology, Department of Clinical Sciences, Skåne University Hospital, Lund University
7Department of Diagnostic Radiology, Oulu University Hospital
8Section of Ophthalmology, Department of Clinical Sciences, Skåne University Hospital, Lund University
9Department of Neurology, Oulu University Hospital
10Research Unit of Clinical Neuroscience, University of Oulu
11Department of Clinical Genetics, Oulu University Hospital
12Section of Pediatric Oncology and Hematology, Department of Clinical Sciences, Skåne University Hospital, Lund University
13Section of Otorhinolaryngology, Department of Clinical Sciences, Skåne University Hospital, Lund University
14Section of Hematology, Department of Clinical Sciences, Skåne University Hospital, Lund University
15Department of Hematology, Linköping University Hospital
16IKE Linköping University
17Division of Molecular Hematology, Institution for Laboratory Medicine, Lund University
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
Persistent link:
Language: English
Published: Wolters Kluwer, 2017
Publish Date: 2017-10-04


Objective: We describe the neurologic, neuroradiologic, and ophthalmologic phenotype of 1 Swedish and 1 Finnish family with autosomal dominant ataxia-pancytopenia (ATXPC) syndrome and SAMD9L mutations.

Methods: Members of these families with germline SAMD9L c.2956C>T, p.Arg986Cys, or c.2672T>C, p.Ile891Thr mutations underwent structured interviews and neurologic and ophthalmologic examinations. Neuroimaging was performed, and medical records were reviewed. Previous publications on SAMD9L-ATXPC were reviewed.

Results: Twelve individuals in both families were affected clinically. All mutation carriers examined had balance impairment, although severity was very variable. All but 1 had nystagmus, and all but 1 had pyramidal tract signs. Neurologic features were generally present from childhood on and progressed slowly. Two adult patients, who experienced increasing clumsiness, glare, and difficulties with gaze fixation, had paracentral retinal dysfunction verified by multifocal electroretinography. Brain MRI showed early, marked cerebellar atrophy in most carriers and variable cerebral periventricular white matter T2 hyperintensities. Two children were treated with hematopoietic stem cell transplantation for hematologic malignancies, and the neurologic symptoms of one of these worsened after treatment. Three affected individuals had attention deficit hyperactivity disorder or cognitive problems. Retinal dysfunction was not previously reported in individuals with ATXPC.

Conclusions: The neurologic phenotype of this syndrome is defined by balance or gait impairment, nystagmus, hyperreflexia in the lower limbs and, frequently, marked cerebellar atrophy. Paracentral retinal dysfunction may contribute to glare, reading problems, and clumsiness. Timely diagnosis of ATXPC is important to address the risk for severe hemorrhage, infection, and hematologic malignancies inherent in this syndrome; regular hematologic follow-up might be beneficial.

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Series: Neurology. Genetics
ISSN: 2376-7839
ISSN-E: 2376-7839
ISSN-L: 2376-7839
Volume: 3
Issue: 5
Article number: e183
DOI: 10.​1212/​NXG.​0000000000000183
Type of Publication: A1 Journal article – refereed
Field of Science: 3112 Neurosciences
3111 Biomedicine
Dataset Reference: Supplementary material can be found at:
Copyright information: Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.