Neuropediatrics 2018; 49(04): 256-261
DOI: 10.1055/s-0038-1649500
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Neonatal Alexander Disease: Novel GFAP Mutation and Comparison to Previously Published Cases

Oula Knuutinen*
1   PEDEGO Research Unit, University of Oulu, Finland
2   Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland
3   Biocenter Oulu, University of Oulu, Finland
,
Maria Kousi*
4   Folkhälsan Institute of Genetics, Helsinki, Finland
5   Center for Human Disease Modeling, Duke University Medical Center, Durham, North Carolina, United States
,
Maria Suo-Palosaari
2   Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland
6   Department of Diagnostic Radiology, Oulu University Hospital, Finland
,
Jukka S. Moilanen
1   PEDEGO Research Unit, University of Oulu, Finland
2   Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland
7   Department of Clinical Genetics, Oulu University Hospital, Finland
,
Hannu Tuominen
8   Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu and Oulu University Hospital, Finland
,
Leena Vainionpää
9   Clinic for Children and Adolescents, Oulu University Hospital, Finland
,
Tarja Joensuu
4   Folkhälsan Institute of Genetics, Helsinki, Finland
10   Neuroscience Center, University of Helsinki, Finland
11   Research Programs Unit, Molecular Neurology, University of Helsinki, Finland
,
Anna-Kaisa Anttonen
4   Folkhälsan Institute of Genetics, Helsinki, Finland
10   Neuroscience Center, University of Helsinki, Finland
11   Research Programs Unit, Molecular Neurology, University of Helsinki, Finland
12   Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Finland
,
Johanna Uusimaa
1   PEDEGO Research Unit, University of Oulu, Finland
2   Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland
3   Biocenter Oulu, University of Oulu, Finland
9   Clinic for Children and Adolescents, Oulu University Hospital, Finland
,
Anna-Elina Lehesjoki#
4   Folkhälsan Institute of Genetics, Helsinki, Finland
10   Neuroscience Center, University of Helsinki, Finland
11   Research Programs Unit, Molecular Neurology, University of Helsinki, Finland
,
Päivi Vieira#
1   PEDEGO Research Unit, University of Oulu, Finland
2   Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland
9   Clinic for Children and Adolescents, Oulu University Hospital, Finland
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Publikationsverlauf

14. Januar 2018

24. März 2018

Publikationsdatum:
25. Mai 2018 (online)

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Abstract

Alexander disease (AxD) is a genetic leukodystrophy caused by GFAP mutations leading to astrocyte dysfunction. Neonatal AxD is a rare phenotype with onset in the first month of life. The proband, belonging to a large pedigree with dominantly inherited benign familial neonatal epilepsy (BFNE), had a phenotype distinct from the rest of the family, with hypotonia and macrocephaly in addition to drug-resistant neonatal seizures. The patient deteriorated and passed away at 6 weeks of age. The pathological and neuroimaging data were consistent with the diagnosis of AxD. Genetic analysis of the proband identified a novel de novo GFAP missense mutation and a KCNQ2 splice site mutation segregating with the BFNE phenotype in the family. The GFAP mutation was located in the coil 2B region of GFAP protein, similar to most neonatal-onset AxD cases with an early death. The clinical and neuroradiological features of the previously published neonatal AxD patients are presented. This study further supports the classification of neonatal-onset AxD as a distinct phenotype based on the age of onset.

Note

The work was performed at Oulu University Hospital, the University of Oulu, and the University of Helsinki.


* Knuutinen and Kousi contributed equally (first author).


# Lehesjoki and Vieira contributed equally (senior author).