Aprosencephaly and cerebellar dysgenesis in sibs

Abstract

Aprosencephaly is a rare, lethal malformation sequence of the central nervous system that has been attributed to a postneuralation encephaloclastic process. We describe autopsy findings consistent with aprosencephaly in 2 fetuses conceived from a consanguineous mating (first cousins). Both showed anencephalic manifestations; however, the crania were intact, with fused sutures. The neuropathologic findings were essentially identical. Each fetus had complete absence of the telecephalon and pyramidal tracts, rudimentary diencephalic and mesencephalic structures, primitive cerebellar hemispheres, posterolateral clusters of primitive neural cells in the medullas suggesting an abnormality of neural migration, a normally‐formed spinal cord, and retinal dysplasia within normally‐formed globes. In addition, both fetuses manifested a peculiar perivascular mesenchymal proliferation seen only within the central nervous system. The similarity of these cases, coupled with parental consanguinity, suggests a primary malformation in brain development due to the homozygous representation of a mutant allele. We hypothesize that these patients may represent a defect in a gene important in brain development, the nature of which has yet to be elucidated. © 1996 Wiley‐Liss, Inc.

First occurrence of aprosencephaly/atelencephaly and holoprosencephaly in a family with a SIX3 gene mutation and phenotype/genotype correlation in our series of SIX3 mutations

“…Interestingly, craniofacial malformations similar to HPE are found in AP/AT and involve the fronto-nasal eminence (ranging from cyclopia/synophthalmia, cebocephaly, and midline cleft to mild hypotelorism or normal face). [11][12][13] Our neuropathological findings in the probands of family 'A' fulfil classical criteria for AP/AT and HPE. Classically in AP/AT and HPE, the midbrain and hindbrain are said to be normal.…”

Atelencephalic microcephaly: a case report and review of the literature

“…All cases with AAS reported so far, except for the two sibs with AAS and cerebellar dysgenesis [3,6], have occurred sporadically. Aprosencephaly and anencephaly in sibs has been described [26].…”

“…Agnathia tissue and that the ventricular system (except for the fourth ventricle) was absent. The cerebellum was intact in 14 cases studied; in two it was hypoplastic and two sibs had a dysgenesis of the cerebellum [3,6].…”

“…Aprosencephaly and anencephaly in sibs has been described [26]. Parental consanguinity was present in the above mentioned sibs [3,6] and in our patient.…”

Holoprosencephaly: Clinical, anatomic, and molecular dimensions

“…Aprosencephaly/atelencephaly is etiologically heterogeneous. It occurs sporadically for the most part, but is also found in the XK‐aprosencephaly syndrome (Renzetti et al,2005); in aneuploidy syndromes, such as del(13q) (Towfighi et al,1987) or r(13) mosaicism (Goldsmith et al,1993); and as a familial, presumably autosomal recessive trait (Townes et al,1988; Florell et al,1996; Labrune et al,1997). Renzetti et al (2005) reported XK‐aprosencephaly in 2 sibs of North African origin.…”