Spinocerebellar ataxia type 2 (SCA2): identification of early brain degeneration in one monozygous twin in the initial disease stage.
Spinocerebellar ataxia type 2 (SCA2) is a progressive autosomal dominantly inherited cerebellar ataxia and is assigned to the CAG repeat or polyglutamine diseases. Recent morphological studies characterized the pathoanatomical features in heterozygous SCA2 patients and revealed severe neuronal loss in a large variety of cerebellar and extra-cerebellar brain sites. In the present study, we examined the brain pathoanatomy of a monozygous twin of a large Hungarian SCA2 family with pathologically extended CAG repeats in both SCA2 alleles. This unique patient was in the initial clinical stage of SCA2 and died almost 3 years after SCA2 onset. Upon pathoanatomical investigation, we observed loss of giant Betz pyramidal cells in the primary motor cortex, degeneration of sensory thalamic nuclei, the Purkinje cell layer, and deep cerebellar nuclei, as well as select brainstem nuclei (i.e., substantia nigra, oculomotor nucleus, reticulotegmental nucleus of the pons, facial, lateral vestibular, and raphe interpositus nuclei, inferior olive). All of these degenerated brain gray matter structures are known as consistent targets of the underlying pathological process in heterozygous SCA2 patients. Since they were already involved in our patient within 3 years after disease onset, we think that we were for the first time able to identify the early brain targets of the pathological process of SCA2.
Institute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Goethe-University, 60590, Frankfurt am Main, Germany.
Franziska
F
Hoche
Laszlo
L
Balikó
Wilfred
W
den Dunnen
Katalin
K
Steinecker
Laszlo
L
Bartos
Eniko
E
Sáfrány
Georg
G
Auburger
Thomas
T
Deller
Horst-Werner
HW
Korf
Thomas
T
Klockgether
Udo
U
Rüb
Bela
B
Melegh
D000230:Adenocarcinoma / Q000150:complications; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000067528:Ataxins; D001921:Brain / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000150:complications; D020754:Spinocerebellar Ataxias / Q000150:complications / Q000235:genetics / Q000473:pathology*; D019680:Trinucleotide Repeat Expansion; D014430:Twins, Monozygotic
D000067528:Ataxins; D009419:Nerve Tissue Proteins