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Ataxia-pancytopenia syndrome with SAMD9L mutations

Authors :
Mikael Karlberg
Karin Nordborg
Andreas Puschmann
Ulrika Kjellström
Johanna Uusimaa
Jörg Cammenga
Christer Nilsson
Ulf Tedgård
Elisa Rahikkala
Josef Davidsson
Jonna Komulainen-Ebrahim
Johanna Krüger
Lennart Nilsson
Maria Suo-Palosaari
Sorina Gorcenco
Dominik Turkiewicz
Sten Andréasson
Source :
Neurology Genetics. 3:e183
Publication Year :
2017
Publisher :
Ovid Technologies (Wolters Kluwer Health), 2017.

Abstract

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.

Details

ISSN :
23767839
Volume :
3
Database :
OpenAIRE
Journal :
Neurology Genetics
Accession number :
edsair.doi.dedup.....a349af5c27fd6acd8f3bf925f994721c
Full Text :
https://doi.org/10.1212/nxg.0000000000000183