Neuroanatomy of holoprosencephaly as predictor of function
Beyond the face predicting the brain
Abstract
Background: Despite advances in neuroimaging and molecular genetics of holoprosencephaly (HPE), the clinical spectrum of HPE has remained inadequately described.
Objective: To better characterize the clinical features of HPE and identify specific neuroanatomic abnormalities that may be useful predictors of neurodevelopmental function.
Methods: The authors evaluated 68 children with HPE in a multicenter, prospective study. Neuroimaging studies were assessed for the grade of HPE (lobar, semilobar, and alobar), the degree of nonseparation of the deep gray nuclei, and presence of dorsal cyst or cortical malformation.
Results: In general, the severity of clinical problems and neurologic dysfunctions correlated with the degree of hemispheric nonseparation (grade of HPE). Nearly three-quarters of the patients had endocrinopathies, with all having at least diabetes insipidus. The severity of endocrine abnormalities correlated with the degree of hypothalamic nonseparation (p = 0.029). Seizures occurred in approximately half of the children with HPE. The presence of cortical malformations was associated with difficult-to-control seizures. The presence and degree of dystonia correlated with the degree of nonseparation of the caudate and lentiform nuclei and the grade of HPE (p < 0.05). Hypotonia correlated with the grade of HPE (p < 0.05). Mobility, upper extremity function, and language correlated with the degree of nonseparation of the caudate, lentiform and thalamic nuclei, and grade of HPE (p < 0.01).
Conclusions: Patients with HPE manifest a wide spectrum of clinical problems and neurologic dysfunction. The nature and severity of many of these problems can be predicted by specific neuroanatomic abnormalities found in HPE.
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References
1.
Golden JA. Towards a greater understanding of the pathogenesis of holoprosencephaly. Brain Dev . 1999; 21: 513–521.
2.
DeMyer W, Zeman W, Palmer CG. The face predicts the brain: diagnostic significance of median facial anomalies for holoprosencephaly (arhinencephaly). Pediatrics . 1964; 34: 256–263.
3.
Simon EM, Hevner R, Pinter JD, et al. Assessment of the deep gray nuclei in holoprosencephaly. AJNR Am J Neuroradiol . 2000; 21: 1955–1961.
4.
Simon EM, Hevner RF, Pinter J, et al. The dorsal cyst in holoprosencephaly and the role of the thalamus in its formation. Neuroradiology . 2001; 43: 787–791.
5.
Simon EM, Hevner RF, Pinter JD, et al. The middle interhemispheric variant of holoprosencephaly. AJNR Am J Neuroradiol . 2002; 23: 151–155.
6.
Barkovich AJ, Simon EM, Clegg NJ, Kinsman SL, Hahn JS. Analysis of the cerebral cortex in holoprosencephaly with attention to the sylvian fissures. AJNR Am J Neuroradiol . 2002; 23: 143–150.
7.
Ming JE, Muenke M. Holoprosencephaly: from Homer to Hedgehog. Clin Genet . 1998; 53: 155–163.
8.
Barr M Jr, Cohen MM Jr. Holoprosencephaly survival and performance. Am J Med Genet . 1999; 89: 116–120.
9.
Sarnat HB, Flores-Sarnat L. Neuropathologic research strategies in holoprosencephaly. J Child Neurol . 2001; 16: 918–931.
10.
Dobyns WB, Reiner O, Carrozzo R, Ledbetter DH. Lissencephaly. A human brain malformation associated with deletion of the LIS1 gene located at chromosome 17p13. JAMA . 1993; 270: 2838–2842.
11.
Cohen MM Jr. Perspectives on holoprosencephaly. Part III. Spectra, distinctions, continuities, and discontinuities. Am J Med Genet . 1989; 34: 271–288.
12.
Hintz RL, Menking M, Sotos JF. Familial holoprosencephaly with endocrine dysgenesis. J Pediatr . 1968; 72: 81–87.
13.
Begleiter ML, Harris DJ. Holoprosencephaly and endocrine dysgenesis in brothers. Am J Med Genet . 1980; 7: 315–318.
14.
Stanhope R, Traggiai C. Endocrinopathies associated with midline cerebral and cranial malformations. J Pediatr . 2002; 140: 252–255.
15.
Hasegawa Y, Hasegawa T, Yokoyama T, Kotoh S, Tsuchiya Y. Holoprosencephaly associated with diabetes insipidus and syndrome of inappropriate secretion of antidiuretic hormone. J Pediatr . 1990; 117: 756–758.
16.
Van Gool S, de Zegher F, de Vries LS, et al. Alobar holoprosencephaly, diabetes insipidus and coloboma without craniofacial abnormalities: a case report. Eur J Pediatr . 1990; 149: 621–622.
17.
Takahashi S, Miyamoto A, Oki J, Saino T, Inyaku F. Alobar holoprosencephaly with diabetes insipidus and neuronal migration disorder. Pediatr Neurol . 1995; 13: 175–177.
18.
Cohen MM Jr, Sulik KK. Perspectives on holoprosencephaly. Part II. Central nervous system, craniofacial anatomy, syndrome commentary, diagnostic approach, and experimental studies. J Craniofac Genet Dev Biol . 1992; 12: 196–244.
19.
Lufkin T, Wang W. The murine Otp homeobox gene plays an essential role in the specification of neuronal cell lineages in the developing hypothalamus. Dev Biol . 2000; 227: 432–449.
20.
DeMyer W. Holoprosencephaly (cyclopia-arhinencephaly). In: Vinken PJ, Bruyn GW, Klawans HL, eds. Handbook of clinical neurology. Revised series, 6th ed. Amsterdam: Elsevier Science Publishers, 1987: 225–244.
21.
Muenke M. Holoprosencephaly: defects of the mediobasal prosencephalon. In: Norman MG, McGillivray BC, Kalousek DK, Hill A, Poskitt KJ, eds. Congenital malformations of the brain: pathological, embryological, clinical, radiological and genetic aspects. New York: Oxford University Press, 1995: 187–221.
22.
Nanni L, Ming JE, Bocian M, et al. The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly. Hum Mol Genet . 1999; 8: 2479–2488.
23.
Wallis D, Muenke M. Mutations in holoprosencephaly. Hum Mutat . 2000; 16: 99–108.
24.
Croen LA, Shaw GM, Lammer EJ. Holoprosencephaly: epidemiologic and clinical characteristics of a California population. Am J Med Genet . 1996; 64: 465–472.
25.
Olsen CL, Hughes JP, Youngblood LG, Sharpe-Stimac M. Epidemiology of holoprosencephaly and phenotypic characteristics of affected children: New York State, 1984–1989. Am J Med Genet . 1997; 73: 217–226.
26.
Ment LR, Pober BR. Neuroembryology. In: McMillan JA, DeAngelis CD, Feigin RD, Warshaw JB, eds. Oski’s pediatrics. 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 1999: 223–229.
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Received: April 15, 2002
Accepted: June 27, 2002
Published online: October 8, 2002
Published in print: October 8, 2002
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