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5 1) Ming J E, Muenke M. Holoprosencephaly; from Homer to Hegehog. Clin Genet 1998; 53: ) Cohen M M Jr. Perspectives on holoprosencephaly: Part I. epidemiology, genetics, and syndromology. Teratology 1989; 40: ) Cohen M M Jr. Perspectives on holoprosencephaly: Part Hi. spectra, distinctions, continuities, and discontinuities. Am J Med Genet 1989; 34: ) Matsunaga E, Shiota K. Holoprosencephaly in hu- embryos: epidemiologic studies of 150 man cases. Teratology 1977; 16: ) Belloni E, Muenke M, Roessler E, et al. Identification of sonic hedgehog as a candidate gene re- sponsible for holoprosencephaly. Nat Genet 1996; 14; ) Rossler E, Belloni E, Gaudenz K, et al. Mutations in the human sonic hedgehog gene cause holoprosencephaly. Nat Genet 1996; 14: ) DeMyer W, Zeman W, Palme C G. The face pre- dicts the brain: diagnostic significance of median facial anomalies for holoprosencephaly (arhinencephaly). Pediatrics 1964; 34: ) Barkovich A J. Pediatric neuroimaging Philadelphia: Lippincott-Raven, 1995: ) Croen L A, Shaw G M, Lammer E J. Holoprosencephaly: epidemiologic and clinical characteris- tics of a California population. Am J Med Genet 1996; 64: ) Olsen C L, Hughes J P, Youngblood L G, Sharpe- Stimac M. Epidemiology of holoprosencephaly and characteristics of affected children: New York State, Am J Med Genet 1997; 73: Whiteford M L, Tolmie J L. Holoprosencephaly in the west of Scotland J Med Genet 1996; 33: ) Rasmussen S A, Moore C A, Khoury M J, Cordero J F. Descriptive epidemiology of holoprosencepha- ly and arhinencephaly in Metropolitan Atlanta, Am J Med Genet 1996; 66: ) Begleiter M L, Harris D J. Brief clinical report: holoprosencephaly and endocrine dysgenesis in brothers. Am J Med Genet 1980; 7:
6 16) Harris E L, Wappner R S, Palmer C G, et al. 7q deletion syndrome (7q32 leads to 7qter). Clin Genet 1977; 12: ) Hasegawa Y, Hasegawa T, Yokoyama T, Katoh S, Tsuchiya Y. Holoprosencephaly associated with di- abetes insipidus and syndrome of inappropriate secretion of antidiuretic hormone. J Pediatr 1990; ) Vogel F, Motulsky A G. Human genetics. Problems and approaches. 3rd ed. Berlin Heidelberg Springer, 1997: Clinical Spectrum and Management of Holoprosencephaly Hiroshi Kawame, M D, Kenji Kurosawa, M D, Akira Akatsuka, M D and Yukikatsu Ochiai, M D Department of Pediatrics, Tokyo Metropolitan Kita Medical & Rehabilitation Center for Handicapped, Tokyo To study the phenotypic spectrum and management of holoprosencephaly (HPE), we reviewed the findings of eight children with HPE from 3 to 10 years of age, who underwent intervention programs and rehabilitation at our center. One patient had alobar HPE, three semilobar HPE, and four lobar HPE. All patients had postnatal growth retardation, and seven showed a decreased BMI (<25% tile). All patients had severe developmental delay and mental retardation (DQ<40), showing no obvious correlation between their severity and the type of HPE. Neurologically seven patients had spasticity (3 spastic quadriplegia, 2 spastic diplegia, 2 mixed-type), except one patient with a 7q deletion [46,XY,del (7) (q35)] who had generalized hypotonia. Seven had variable types of seizures. All patients had feeding difficulties and were assessed by speech-language therapists. Four patients required tube feeding, four had gastroesophageal reflux disease. Recurrent respiratory tract infection was common. Three patients had abnormal serum sodium concentration (1 diabetes insipidus, 1 idiopathic hypernatremia, 1 hyponatremia). No family history of HPE was elicited. In conclusion, patients with HPE should be followed up closely for complications such as feeding difficulty, malnutrition, seizures, spasticity, infection, and osmoreceptor-hypothalamus-hypophyseal axis abnormalities. No To Hattatsu 2000; 32: 301-6
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