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

Oula Knuutinen; Maria Kousi; Maria Suo-Palosaari; Jukka S. Moilanen; Hannu Tuominen; Leena Vainionpää; Tarja Joensuu; Anna-Kaisa Anttonen; Johanna Uusimaa; Anna-Elina Lehesjoki; Päivi Vieira

doi:10.1055/s-0038-1649500

Neuropediatrics, Table of Contents

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^*

¹PEDEGO Research Unit, University of Oulu, Finland

²Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland

³Biocenter Oulu, University of Oulu, Finland

,

Maria Kousi^*

⁴Folkhälsan Institute of Genetics, Helsinki, Finland

⁵Center for Human Disease Modeling, Duke University Medical Center, Durham, North Carolina, United States

,

Maria Suo-Palosaari

²Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland

⁶Department of Diagnostic Radiology, Oulu University Hospital, Finland

,

Jukka S. Moilanen

¹PEDEGO Research Unit, University of Oulu, Finland

²Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland

⁷Department of Clinical Genetics, Oulu University Hospital, Finland

,

Hannu Tuominen

⁸Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu and Oulu University Hospital, Finland

,

Leena Vainionpää

⁹Clinic for Children and Adolescents, Oulu University Hospital, Finland

,

Tarja Joensuu

⁴Folkhälsan Institute of Genetics, Helsinki, Finland

¹⁰Neuroscience Center, University of Helsinki, Finland

¹¹Research Programs Unit, Molecular Neurology, University of Helsinki, Finland

,

Anna-Kaisa Anttonen

⁴Folkhälsan Institute of Genetics, Helsinki, Finland

¹⁰Neuroscience Center, University of Helsinki, Finland

¹¹Research Programs Unit, Molecular Neurology, University of Helsinki, Finland

¹²Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Finland

,

Johanna Uusimaa

¹PEDEGO Research Unit, University of Oulu, Finland

²Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland

³Biocenter Oulu, University of Oulu, Finland

⁹Clinic for Children and Adolescents, Oulu University Hospital, Finland

,

Anna-Elina Lehesjoki^#

⁴Folkhälsan Institute of Genetics, Helsinki, Finland

¹⁰Neuroscience Center, University of Helsinki, Finland

¹¹Research Programs Unit, Molecular Neurology, University of Helsinki, Finland

,

Päivi Vieira^#

¹PEDEGO Research Unit, University of Oulu, Finland

²Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland

⁹Clinic for Children and Adolescents, Oulu University Hospital, Finland

› Author Affiliations

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.

Keywords

drug-resistant seizures - hydrocephalus - neuroimaging - leukodystrophy

Full Text

References

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