Development and developmental disorders of the human cerebellum

Abstract

The human cerebellum develops over a long time, extending from the early embryonic period until the first postnatal years. This protracted development makes the cerebellum vulnerable to a broad spectrum of developmental disorders. The development of the cerebellum occurs in four basic steps: 1) characterization of the cerebellar territory at the midbrain-hindbrain boundary; 2) formation of two compartments for cell proliferation: first, the Purkinje cells and the deep cerebellar nuclei arise from the ventricular zone of the metencephalic alar plate; second, granule cell precursors are formed from a second compartment of proliferation, i. e. the upper rhombic lip; 3) inward migration of the granule cells: granule precursor cells form the external granular layer, from which (and continuing into the first postnatal year), granule cells migrate inwards to their definite position in the internal granular layer, and 4) formation of cerebellar circuitry and further differentiation. The precerebellar nuclei, i. e. the pontine nuclei and the inferior olive, arise from the lower rhombic lip. Developmental disorders of the cerebellum are often accompanied by malformations of the precerebellar nuclei. In this review the development of the cerebellum and some of its more frequent developmental disorders, such as the Dandy-Walker and related midline malformations, and the pontocerebellar hypoplasias, are discussed.

Nomograms of the axial fetal cerebellar hemisphere circumference and area throughout gestation

“…Bromley et al established sonographically that at 14 weeks of gestation, 56% of fetuses had an open vermis, decreasing to 23% and 6% at 15 and 17 weeks, respectively 14 . Overall, development of the human cerebellum extends from the early embryonic period through the first postnatal years 15 . In addition, developmental disorders of the cerebellum are often accompanied by malformations of the precerebellar nuclei 15 .…”

“…Overall, development of the human cerebellum extends from the early embryonic period through the first postnatal years 15 . In addition, developmental disorders of the cerebellum are often accompanied by malformations of the precerebellar nuclei 15 . Congenital abnormalities of the cerebellum are associated with fetal aneuploidies 16 -20 , hypoplasia (including Dandy-Walker malformation) 21 -23 , congenital cytomegalic infection 24 , and a wide spectrum of syndromes (Meckel-Gruber, Neu-Laxova, Walker-Warburg, Joubert, Williams, and acrocallosal syndromes, among others) 25,26 .…”

A Newborn with Dandy-Walker Malformation and Aortic Coarctation

“…Dandy-Walker malformation (DWM), a congenital anomaly of the posterior cranial fossa, characterized by the triad of cystic dilatation of the fourth ventricle, enlarged posterior fossa, and complete or partial agenesis or absence of the cerebellar vermis and hydrocephalus (1,2). The malformation occurs in approximately 1 per 25.000 live births, more frequently in girls than in boys (3).…”

Malformação de Dandy-Walker

“…Porém, sabe-se que a natureza para tais malformações é o processo de desenvolvimento das estruturas da fossa posterior; 6 além disso, recentemente identificou-se um gene X-HPRT associado tanto à malformação de Dandy-Walker quanto às doenças de gânglios da base. 7,8 A teoria mais aceita para explicar sua patogenia envolve o processo de desenvolvimento da folha dos forames de Lushka e Magendie durante o quarto mês de vida fetal, o que leva ao abaulamento cístico do quarto ventrículo. 7 Murray et al enfatizaram a etiologia heterogênea relacionada à síndrome de Dandy Walker.…”

“…7,8 A teoria mais aceita para explicar sua patogenia envolve o processo de desenvolvimento da folha dos forames de Lushka e Magendie durante o quarto mês de vida fetal, o que leva ao abaulamento cístico do quarto ventrículo. 7 Murray et al enfatizaram a etiologia heterogênea relacionada à síndrome de Dandy Walker. Há um baixo risco de recorrência, em torno de 1 a 5%, quando a malformação ocorre isoladamente.…”