Cerebellar Hypoplasia with Heterotopic Purkinje Cells in the Molecular Layer and Preservation of the Granule Layers Associated with Severe Encephalopathy. A New Entity?

Abstract

We present the case of an infant girl, born to first cousins, with a clinical phenotype consisting of microcephaly, hypotonia, strabismus and severe psychomotor retardation. Magnetic resonance imaging (MRI) showed global cerebellar atrophy involving the vermis and both hemispheres. The patient's serum transferrin levels were consistently unremarkable. Cerebellar biopsy, performed at 13 months of age, revealed heterotopic Purkinje cells in the molecular layer, but preservation of the external and internal granular layers. To our knowledge, this histological pattern of cerebellar cortical disorganization has not been described previously. The consanguinity of the parents suggests an autosomal recessive inheritance.

Cerebellum - hypoplasia - basket fibres - heterotopic Purkinje cells - mental retardation - hypotonia - calbindin-D_28k - tubulin - neurofilaments - psychomotor retardation

References

• 1 Arsenio Nunes M L, Sotelo C, Wehrle R. Organization of spinocerebellar projection map in three types of granular cerebellum: Purkinje cells vs. granule cells as organizer element.  J Comp Neurol. 1988;  273 120-136
• 2 Friede R L. Developmental Neuropathology. Berlin; Springer-Verlag 1989: 366-369
• 3 Goffinet A M. The embryonic development of the cerebellum in normal and reeler mutant mice.  Anat Embryol (Berl). 1983;  168 73-86
• 4 Goldowitz E, Hemre K. The cells and molecules that make a cerebellum.  Tends Neurosci. 1998;  21 375-382
• 5 Jaeken J, Carchon H. Congenital disorders of glycosylation: the rapidly growing tip of the iceberg.  Curr Opin Neurol. 2001;  14 811-815
• 6 Katsetos C SD, Frankfurter A, Christakos S, Mancall E L, Vlachos I N, Urich H. Differential localization of class III B-tubulin isotype and calbindin-D28 k defines distinct neuronal types in the developing human cerebellar cortex.  J Neuropathol Exp Neurol. 1993;  52 655-666
• 7 Millen K J, Millonig J H, Wingate R J, Alder J, Hatten M E. Neurogenetics of the cerebellar system.  J Child Neurol. 1999;  14 574-581
• 8 Norman R M. Primary degeneration of the granular layer of the cerebellum: An unusual form of familial cerebellar atrophy occurring in early life.  Brain. 1940;  63 365-379
• 9 Pascual-Castroviejo I, Gutierrez M, Morales C, Gonzalez-Mediero I, Martinez-Bermejo A, Pascual-Pascual S I. Primary degeneration of the granular layer of the cerebellum. A study of 14 patients and review of the literature.  Neuropediatrics. 1994;  25 185-190
• 10 Pascual-Castroviejo I. Congenital disorders of glycosylation syndromes.  Dev Med Child Neurol. 2002;  44 357-358
• 11 Sarnat H B, Menkes J H. How to construct a neural tube.  J Child Neurol. 2000;  15 110-124
• 12 Shiurba R A, Gessaga E C, Eng L F, Sternberger N H, Sternberger L A, Urich H. Lhermitte-Duclos disease. An inmunohistochemical study of the cerebellar cortex.  Acta Neuropathol (Berl). 1988;  75 474-480
• 13 Urich H. Malformations of the nervous system. Blackwood W, Corsellis JAN Grenfield's Neuropathology. 3rd ed. London; Edward Arnold 1977: 361-469
• 14 Zecevic N, Rakic P. Differentiation of Purkinje cells and their relationship to other components of developing cerebellar cortex in man.  J Comp Neurol. 1976;  167 27-47