Clinical progression and genetic analysis in hereditary spastic paraplegia with thin corpus callosum in spastic gait gene 11 (SPG11).
BACKGROUND
Hereditary spastic paraplegia (HSP) with thin corpus callosum (CC) is a rare neurodegenerative disorder classified as a complicated form of spastic paraplegia. Some patients with HSP with thin CC have previously been described in Japanese families, and the genetic locus was linked to chromosome 15q13-15.


OBJECTIVE
Our objective was to further clinically and genetically characterize HSP with thin CC.


METHODS
We describe the clinical, structural, and functional follow-up and the genetic characterization of 2 sisters aged 26 and 31 years who had severe spastic paraplegia and cognitive impairment.


RESULTS
Magnetic resonance imaging revealed a thin CC with progressing frontoparietal cortical atrophy paralleled by cognitive decline. Using transcranial magnetic stimulation, we delineated a lack of transcallosal inhibition. Images obtained with(18)fluorodeoxyglucose positron emission tomography showed reduced cortical and thalamic hypometabolism that decreased further within 4 years. Additionally, combined axonal loss and demyelinating sensorimotor polyneuropathy were present. Because other family members were not affected, autosomal recessive inheritance was considered likely. Genetic analysis of this autosomal recessive HSP was consistent with the linkage to 15q13-15 (markers D15S971, D15S118, D15S994, and D15S659). No mutation was found within the SLC12A6 gene.


CONCLUSIONS
Progressive axonal degeneration occurs in the corticocortical projections, corticospinal tract, and peripheral nerves in HSP with thin CC linking to chromosome 15q13-15 in a German pedigree.
Winner
Beate
B
Department of Neurology, University of Regensburg, Universitätsstrasse 84, D-93053 Regensburg, Germany.
Uyanik
Goekhan
G
Gross
Claudia
C
Lange
Max
M
Schulte-Mattler
Wilhelm
W
Schuierer
Gerhard
G
Marienhagen
Joerg
J
Hehr
Ute
U
Winkler
Juergen
J
D000328:Adult; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics; D003337:Corpus Callosum / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D020233:Gait Disorders, Neurologic / Q000235:genetics; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology; D010375:Pedigree; D011115:Polyneuropathies / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D014055:Tomography, Emission-Computed