Journal of Neurology

, Volume 264, Issue 1, pp 11–20 | Cite as

ALS and MMN mimics in patients with BSCL2 mutations: the expanding clinical spectrum of SPG17 hereditary spastic paraplegia

  • Thomas Musacchio
  • Ann-Kathrin Zaum
  • Nurcan Üçeyler
  • Claudia Sommer
  • Nora Pfeifroth
  • Karlheinz Reiners
  • Erdmute Kunstmann
  • Jens Volkmann
  • Simone Rost
  • Stephan KlebeEmail author
Original Communication


Silver syndrome/SPG17 is a motor manifestation of mutations in the BSCL2 gene and usually presents as a complicated form of hereditary spastic paraplegia (HSP). We present clinical data, follow-up, and genetic results of seven patients with Silver syndrome/SPG17 including a family with a variable intrafamilial phenotype ranging from subclinical signs to a severe and rapidly progressing amyotrophic lateral sclerosis (ALS)-like phenotype. For molecular diagnosis of the family, we used the TruSight Exome sequencing panel consisting of 2761 genes. We filtered for variants common to affected family members and for exclusive variants in the ALS-like index patient to find possible modifier mutations. We found that de novo mutations and/or incomplete penetrance in BSCL2 has been taken into account for Silver syndrome/SPG17 and confirm the large phenotypical heterogeneity of BSCL2 mutations. Our findings broaden the reported spectrum of the disease to an ALS-like and multifocal motor neuropathy phenotype and underline the need for further research for genetic modifiers due to the striking interindividual and intrafamilial variability.


Hereditary spastic paraplegia SPG17 BSCL2 


Compliance with ethical standards

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standard

This study followed ethical standards in conducting all diagnostic procedures. The patients were informed about the Intention to publish the cases report and gave their written consent.

Supplementary material

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Supplementary material 1 (MP4 24101 kb)
415_2016_8301_MOESM2_ESM.docx (30 kb)
Supplementary material 2 (DOCX 29 kb)
415_2016_8301_MOESM3_ESM.docx (16 kb)
Supplementary material 3 (DOCX 15 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Thomas Musacchio
    • 1
  • Ann-Kathrin Zaum
    • 2
  • Nurcan Üçeyler
    • 1
  • Claudia Sommer
    • 1
  • Nora Pfeifroth
    • 1
  • Karlheinz Reiners
    • 1
  • Erdmute Kunstmann
    • 2
  • Jens Volkmann
    • 1
  • Simone Rost
    • 2
  • Stephan Klebe
    • 1
    • 3
    Email author
  1. 1.Department of NeurologyUniversity Hospital WürzburgWürzburgGermany
  2. 2.Department of Human GeneticsUniversity of WürzburgWürzburgGermany
  3. 3.Department of NeurologyUniversity Hospital FreiburgFreiburgGermany

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