Abstract
Acrocallosal syndrome (ACS) is an autosomal recessive disorder characterized by craniofacial dysmorphism, agenesis or hypoplasia of the corpus callosum, duplication of the phalanges of the hallux, more rarely the thumbs, post-axial polydactyly, syndactyly and severe mental retardation. Here we report the two first descriptions of acrocallosal syndrome in fetus with extensive neuropathological study and provide new data regarding additional brain abnormalities in ACS. The first case was a 25-gestational week male fetus displaying craniofacial and limb abnormalities, with bilateral syndactyly of the fourth and fifth fingers, preaxial polydactyly of the left foot and an inter-frontal extra-bone. The second fetus was a 33-gestational week male fetus. His left hand displayed a broad thumb and 4/5 syndactyly. In both cases, gross examination of the brain showed an absence of corpus callosum associated with interhemispheric cysts. The cerebral cortex in front of the cysts was nodular. Upon microscopic examination, the nodular masses corresponded to large dysplastic areas represented by clusters of undifferentiated neurons in the white matter. The cyst wall showed arachnoidal and ependymal covering and contained numerous choroid plexus, suggesting a developmental abnormality of the ventricles. The pons and the cerebellum were hypoplastic. The dentate nuclei were fragmented. Numerous neuronal heterotopias associated with ectopic ependymal cavities were observed in the vermis in one case. The olivary nuclei were severely dysplastic too. We hope that these new data will make both the ante- and post-natal diagnosis easier, facilitate comparisons with animal models and encourage the identification of the genes responsible for this syndrome.
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References
Brueton LA, Chotai KA, van Herwerden L, Schinzel A, Winter RM (1992) The acrocallosal syndrome and Greig syndrome are not allelic disorders. J Med Genet 29:635–637
Casamassima AC, Beneck D, Gewitz MH, Horowitz MA, Woolf PK, Pettersen IM, Shapiro LR (1989) Acrocallosal syndrome: additional manifestations. Am J Med Genet 32:311–317
Chiang C, Litingtung Y, Lee E, Young KE, Corden JL, Westphal H, Beachy PA (1996) Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383:407–413
Christianson AL, Venter PA, Du Toit JL, Shipalana N, Gericke GS (1994) Acrocallosal syndrome in two African brothers born to consanguineous parents. Am J Med Genet 51:98–101
Courtens W, Vamos E, Christophe C, Schinzel A (1997) Acrocallosal syndrome in an Algerian boy born to consanguineous parents: review of the literature and further delineation of the syndrome. Am J Med Genet 69:17–22
Dahmane N, Sanchez P, Gitton Y, Palma V, Sun T, Beyna M, Weiner H, Ruiz i Altaba A (2001) The Sonic Hedgehog-Gli pathway regulates dorsal brain growth and tumorigenesis. Development 128:5201–5212
Docherty Z, Seller MJ (1993) Acrocallosal syndrome and 12p. Ann Genet 36:136
Elson E, Perveen R, Donnai D, Wall S, Black GC (2002) De novo GLI3 mutation in acrocallosal syndrome: broadening the phenotypic spectrum of GLI3 defects and overlap with murine models. J Med Genet 39:804–806
Gelman-Kohan Z, Antonelli J, Ankori-Cohen H, Adar H, Chemke J (1991) Further delineation of the acrocallosal syndrome. Eur J Pediatr 150:797–799
Hendriks HJ, Brunner HG, Haagen TA, Hamel BC (1990) Acrocallosal syndrome. Am J Med Genet 35:443–446
Hui CC, Joyner AL (1993) A mouse model of greig cephalopolysyndactyly syndrome: the extra-toesJ mutation contains an intragenic deletion of the Gli3 gene. Nat Genet 3:241–246
Johnston JJ, Olivos-Glander I, Turner J, Aleck K, Bird LM, Mehta L, Schimke RN, Heilstedt H, Spence JE, Blancato J, Biesecker LG (2003) Clinical and molecular delineation of the Greig cephalopolysyndactyly contiguous gene deletion syndrome and its distinction from acrocallosal syndrome. Am J Med Genet A 123:236–242
Kalff-Suske M, Wild A, Topp J, Wessling M, Jacobsen EM, Bornholdt D, Engel H, Heuer H, Aalfs CM, Ausems MG, Barone R, Herzog A, Heutink P, Homfray T, Gillessen-Kaesbach G, Konig R, Kunze J, Meinecke P, Muller D, Rizzo R, Strenge S, Superti-Furga A, Grzeschik KH (1999) Point mutations throughout the GLI3 gene cause Greig cephalopolysyndactyly syndrome. Hum Mol Genet 8:1769–1777
Koenig R, Bach A, Woelki U, Grzeschik KH, Fuchs S (2002) Spectrum of the acrocallosal syndrome. Am J Med Genet 108:7–11
Pfeiffer RA, Legat G, Trautmann U (1992) Acrocallosal syndrome in a child with de novo inverted tandem duplication of 12p11.2-p13.3. Ann Genet 35:41–46
Rauch A, Trautmann U, Pfeiffer RA (1996) Clinical and molecular cytogenetic observations in three cases of “trisomy 12p syndrome. Am J Med Genet 63:243–249
Ruiz i Altaba A (1999) Gli proteins encode context-dependent positive and negative functions: implications for development and disease. Development 126:3205–3216
Schinzel A (1988) The acrocallosal syndrome in first cousins: widening of the spectrum of clinical features and further support for autosomal recessive inheritance. J Med Genet 25:332–336
Schinzel A (1982) Four patients including two sisters with the acrocallosal syndrome (agenesis of the corpus callosum in combination with preaxial hexadactyly). Hum Genet 62:382
Schinzel A (1979) Postaxial polydactyly, hallux duplication, absence of the corpus callosum, macrencephaly and severe mental retardation: a new syndrome? Helv Paediatr Acta 34:141–146
Schinzel A, Kaufmann U (1986) The acrocallosal syndrome in sisters. Clin Genet 30:399–405
Sueldo G, Fernandes MC (1993) Fronto-nasal dysostosis, callosal agenesis, crossed-fused ectopia, tibial hemimelia, and preaxial polydactyly of feet: severe expression of the acrocallosal syndrome? Am J Med Genet 46:355–357
Thyen U, Aksu F, Bartsch O, Herb E (1992) Acrocallosal syndrome: association with cystic malformation of the brain and neurodevelopmental aspects. Neuropediatrics 23:292–296
Vortkamp A, Franz T, Gessler M, Grzeschik KH (1992) Deletion of GLI3 supports the homology of the human Greig cephalopolysyndactyly syndrome (GCPS) and the mouse mutant extra toes (Xt). Mamm Genome 3:461–463
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We thank M. Auphan and P. Morando for excellent technical assistance.
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Fernandez, C., Soulier, M., Coulibaly, B. et al. Acrocallosal syndrome in fetus: focus on additional brain abnormalities. Acta Neuropathol 115, 151–156 (2008). https://doi.org/10.1007/s00401-007-0249-y
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DOI: https://doi.org/10.1007/s00401-007-0249-y