Hypomyelination with atrophy of the basal ganglia and cerebellum: follow-up and pathology.
OBJECTIVE
Hypomyelination with atrophy of the basal ganglia and cerebellum is a recently defined disorder. Only a few patients have been described. We report on 11 additional patients and new MRI findings and provide histopathologic confirmation of the MRI interpretation.


METHODS
We reviewed the patients' clinical history and present findings. We scored the MRI abnormalities. The histopathology of one patient was re-examined.


RESULTS
The patients' early psychomotor development was normal or delayed, followed by increasing extrapyramidal movement abnormalities, ataxia, and spasticity. Mental capacities were variably affected. MRI showed hypomyelination with, on follow-up, evidence of further myelin loss and variable white matter atrophy. The putamen was small or, more often, absent; the head of the caudate nucleus was decreased in size. In contrast, the thalamus and globus pallidus remained normal. Cerebellar atrophy was invariably present. Histopathology confirmed the myelin deficiency, probably related to both lack of deposition and low-grade further loss. The degeneration of putamen was subtotal. The cerebellar cortex was affected, particularly the granular layer.


CONCLUSIONS
Hypomyelination with atrophy of the basal ganglia and cerebellum is a syndrome diagnosed by distinctive MRI findings. Histopathology confirms hypomyelination, low-grade further myelin loss, subtotal degeneration of the putamen, and cerebellar cortical atrophy. All known patients are sporadic, and the mode of inheritance is unclear.
van der Knaap
M S
MS
Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands. ms.vanderknaap@vumc.nl
Linnankivi
T
T
Paetau
A
A
Feigenbaum
A
A
Wakusawa
K
K
Haginoya
K
K
Köhler
W
W
Henneke
M
M
Dinopoulos
A
A
Grattan-Smith
P
P
Brockmann
K
K
Schiffmann
R
R
Blaser
S
S
D001284:Atrophy / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D001479:Basal Ganglia / Q000473:pathology* / Q000503:physiopathology; D001480:Basal Ganglia Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D002526:Cerebellar Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D002531:Cerebellum / Q000473:pathology* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D020271:Heredodegenerative Disorders, Nervous System / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D011237:Predictive Value of Tests; D013577:Syndrome