BACKGROUND AND PURPOSE: Although holoprosencephaly has been known for many years, few detailed analyses have been performed in a large series of patients to outline the range of morphology in this disorder, particularly regarding the deep gray nuclear structures. We reviewed a large patient cohort to elucidate the combinations of morphologic aberrations of the deep gray nuclei and to correlate those findings with recent discoveries in embryology and developmental neurogenetics. METHODS: A retrospective review of the imaging records of 57 patients (43 MR studies and 14 high-quality CT studies) to categorize the spectrum of deep gray nuclear malformations. The hypothalami, caudate nuclei, lentiform nuclei, thalami, and mesencephalon were graded as to their degree of noncleavage. Spatial orientation was also evaluated, as was the relationship of the basal ganglia to the diencephalic structures and mesencephalon. The extent of noncleavage of the various nuclei was then assessed for statistical association. RESULTS: In every study on which it could be accurately assessed, we found some degree of hypothalamic noncleavage. Noncleavage was also common in the caudate nuclei (96%), lentiform nuclei (85%), and thalami (67%). Complete and partial noncleavage were more common in the caudate nuclei than in the lentiform nuclei. The degree of thalamic noncleavage was uniformly less than that in the caudate and lentiform nuclei. Abnormalities in alignment of the long axis of the thalamus were seen in 71% of cases, and were associated with degree of thalamic noncleavage; 27% of patients had some degree of mesencephalic noncleavage. CONCLUSION: The hypothalamus and caudate nuclei are the most severely affected structures in holoprosencephaly, and the mesencephalic structures are more commonly involved than previously thought in this "prosencephalic disorder." These findings suggest the lack of induction of the most rostral aspects of the embryonic floor plate as the cause of this disorder.
BACKGROUND AND PURPOSE: Although holoprosencephaly has been known for many years, few detailed analyses have been performed in a large series of patients to outline the range of morphology in this disorder, particularly regarding the deep gray nuclear structures. We reviewed a large patient cohort to elucidate the combinations of morphologic aberrations of the deep gray nuclei and to correlate those findings with recent discoveries in embryology and developmental neurogenetics. METHODS: A retrospective review of the imaging records of 57 patients (43 MR studies and 14 high-quality CT studies) to categorize the spectrum of deep gray nuclear malformations. The hypothalami, caudate nuclei, lentiform nuclei, thalami, and mesencephalon were graded as to their degree of noncleavage. Spatial orientation was also evaluated, as was the relationship of the basal ganglia to the diencephalic structures and mesencephalon. The extent of noncleavage of the various nuclei was then assessed for statistical association. RESULTS: In every study on which it could be accurately assessed, we found some degree of hypothalamic noncleavage. Noncleavage was also common in the caudate nuclei (96%), lentiform nuclei (85%), and thalami (67%). Complete and partial noncleavage were more common in the caudate nuclei than in the lentiform nuclei. The degree of thalamic noncleavage was uniformly less than that in the caudate and lentiform nuclei. Abnormalities in alignment of the long axis of the thalamus were seen in 71% of cases, and were associated with degree of thalamic noncleavage; 27% of patients had some degree of mesencephalic noncleavage. CONCLUSION: The hypothalamus and caudate nuclei are the most severely affected structures in holoprosencephaly, and the mesencephalic structures are more commonly involved than previously thought in this "prosencephalic disorder." These findings suggest the lack of induction of the most rostral aspects of the embryonic floor plate as the cause of this disorder.
Authors: D E Wallis; E Roessler; U Hehr; L Nanni; T Wiltshire; A Richieri-Costa; G Gillessen-Kaesbach; E H Zackai; J Rommens; M Muenke Journal: Nat Genet Date: 1999-06 Impact factor: 38.330
Authors: J A Golden; A Bracilovic; K A McFadden; J S Beesley; J L Rubenstein; J B Grinspan Journal: Proc Natl Acad Sci U S A Date: 1999-03-02 Impact factor: 11.205
Authors: S A Brown; D Warburton; L Y Brown; C Y Yu; E R Roeder; S Stengel-Rutkowski; R C Hennekam; M Muenke Journal: Nat Genet Date: 1998-10 Impact factor: 38.330
Authors: Erin M Simon; Robert F Hevner; Joseph D Pinter; Nancy J Clegg; Mauricio Delgado; Stephen L Kinsman; Jin S Hahn; A James Barkovich Journal: AJNR Am J Neuroradiol Date: 2002-01 Impact factor: 3.825
Authors: David Phillips; David A Steven; Patrick J McDonald; Jay Riva-Cambrin; Abhaya V Kulkarni; Vivek Mehta Journal: Childs Nerv Syst Date: 2019-06-06 Impact factor: 1.475
Authors: A James Barkovich; Erin M Simon; Nancy J Clegg; Steven L Kinsman; Jin S Hahn Journal: AJNR Am J Neuroradiol Date: 2002-01 Impact factor: 3.825