Clinical neurophysiology in GJA12-related hypomyelination vs Pelizaeus-Merzbacher disease.
BACKGROUND
Among the hypomyelinating leukoencephalopathies with onset in childhood, Pelizaeus-Merzbacher disease (PMD) and Pelizaeus-Merzbacher-like disease (PMLD) constitute a large subgroup with almost indistinguishable clinical and neuroradiologic features. Whereas PMD is due to X-linked PLP1 mutations, PMLD is genetically heterogeneous, with about 8% of patients carrying autosomal recessive GJA12/GJC2 mutations. The aim of this study was to evaluate whether neurophysiologic testing may separate PMD from GJA12/GJC2-associated PMLD.


METHODS
Retrospective data collection study with reevaluation of evoked potentials (EP) and nerve conduction studies (NCS) in 10 patients from 7 families with PMLD due to various GJA12/GJC2 mutations and 8 boys from 7 families with classic PMD caused by a PLP1 duplication or missense mutation.


RESULTS
In brainstem auditory EP, waves III-V were absent in all patients with PMD, but clearly recordable in 11 of 13 investigations in 8 patients with PMLD. Visual evoked potentials and somatosensory evoked potentials revealed conduction delay in both PMD and PMLD, without significant difference. NCS were normal in all patients with PMD and indicated mild peripheral neuropathy in only 2 of 10 patients with PMLD.


CONCLUSIONS
In a patient with clinical and neuroradiologic features of Pelizaeus-Merzbacher disease/Pelizaeus-Merzbacher-like disease and a pedigree consistent with both conditions, brainstem auditory evoked potentials provide good selectivity between these disorders and point in the right direction for identifying the primary genetic defect.
Department of Pediatrics and Pediatric Neurology, Georg August University, Robert Koch Str. 40, 37075 Göttingen, Germany.
M
M
Henneke
S
S
Gegner
A
A
Hahn
B
B
Plecko-Startinig
B
B
Weschke
J
J
Gärtner
K
K
Brockmann
D000293:Adolescent; D000328:Adult; D001933:Brain Stem / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D017630:Connexins / Q000235:genetics*; D005071:Evoked Potentials / Q000502:physiology; D005192:Family Health; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009431:Neural Conduction / Q000502:physiology; D020371:Pelizaeus-Merzbacher Disease / Q000503:physiopathology*; D010812:Physical Stimulation / Q000379:methods; D012189:Retrospective Studies; D055815:Young Adult
D017630:Connexins; C427305:connexin 47