Highlights
- •Thumb abnormalities in patients with SYNE1 mutations.
- •Lobulated myonuclei were a consistent ultrastructural feature.
- •Nuclear envelope pathology not only in myonuclei but also in Schwann cells nuclei.
- •Schwann cell nuclei are affected, indicating the neurodegenerative phenotype.
Abstract
Aims
To define the neurological and neuropathological alterations caused by SYNE1 mutations.
Methods
We describe 5 patients (3 males, 2 females; age 3–24 years) from 3 families. The diagnostic
work-up included three muscle biopsies and two nerve biopsies in three of the cases.
Results
Three different phenotypes were discerned. Two patients showed progressive ataxia,
mental retardation, neuropathy and radially deviated thumbs (spinocerebellar ataxia,
SCAR, type 8 phenotype). Two patients had mild congenital myopathy with restrictive
lung disease, clubfeet and thumb anomalies (myopathic arthrogryposis). One patient
had congenital myopathy with dilated cardiomyopathy and adducted thumbs (Emery-Dreifuss
Muscular Dystrophy, EDMD, type 4). Light microscopy of the three muscle biopsies revealed
chronic non-necrotizing myopathy without rimmed vacuoles in all cases combined with
neurogenic atrophy in one case. The two nerve biopsies showed predominantly axonal
neuropathy with demyelinating features. Nuclear alterations, most notably lobulation
and focal widening of the space between inner and outer leaflet of the nuclear envelope,
were a prominent consistent feature of myonuclei and Schwann cell nuclei in each of
the three muscle specimens and one nerve specimen that could be examined by electron
microscopy.
Conclusion
Thumb abnormalities and nuclear envelope alterations are characteristic for SYNE 1 mutations. Schwann cell nuclei are affected, indicating that such nuclear envelope
changes in glial cells contribute to the neurodegenerative phenotype in human nesprinopathies.
Keywords
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Article info
Publication history
Published online: December 29, 2018
Accepted:
December 22,
2018
Received in revised form:
December 18,
2018
Received:
August 25,
2018
Identification
Copyright
© 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
