{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T20:15:33Z","timestamp":1789935333960,"version":"4.0.1"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,6,7]],"date-time":"2005-06-07T00:00:00Z","timestamp":1118102400000},"content-version":"vor","delay-in-days":4724,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Med. Genet."],"published-print":{"date-parts":[[1992,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We report on a case of neonatal hypothalamic hamartoblastoma with holoprosencephaly, Hirschsprung disease, and tetramelic postaxial polydactyly. Twenty\u2010seven previous cases of congenital hypothalamic embryonic tumours with associated congenital defects are reviewed. A classification in isolated, associated, and syndromal forms is proposed. The difficulties encountered in differential diagnosis between the syndromal form (mainly represented by the Pallister\u2010Hall syndrome) and related diseases as Smith\u2010Lemli\u2010Opitz type II, holoprosencephaly\u2010polydactyly, orofaciodigital type VI and hydrolethalus syndromes are outlined. Two pathogenic mechanisms are discussed: a classical pleiotropic model and single sequence model. The latter is sufficient to delineate syndromal hypothalamic hamartoblastoma. With the former, syndromal hypothalamic hamartoblastoma cannot be clearly recognized in the absence of a CNS tumour, a child with syndromal hypothalamic hamartoblastoma cannot be reliably diagnosed as Pallister\u2010Hall rather than another MCA syndrome, and, ultimately, the existence of Pallister\u2010Hall syndrome could be questioned, as it could only be the extreme expression of one or several other syndromes. As this hypothesis cannot be proven or disproven at this point, the authors suggest creating the concept of multiplex phenotype. \u201cCerebro\u2010Acro\u2010Visceral Early lethality multiplex syndrome\u201d is suggested to encompass all the ambiguous cases. Within this complex, an operative classification key is proposed. \u00a9 1992 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.1320430404","type":"journal-article","created":{"date-parts":[[2005,6,12]],"date-time":"2005-06-12T04:43:49Z","timestamp":1118551429000},"page":"669-677","source":"Crossref","is-referenced-by-count":32,"title":["Variability versus heterogeneity in syndromal hypothalamic hamartoblastoma and related disorders: Review and delineation of the Cerebro\u2010Acro\u2010Visceral Early lethality (CAVE) multiplex syndrome"],"prefix":"10.1002","volume":"43","author":[{"given":"Alain","family":"Verloes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Gillerot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Paul","family":"Langhendries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Pierre","family":"Fryns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucien","family":"Koulischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,6,7]]},"reference":[{"key":"e_1_2_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320260418"},{"key":"e_1_2_2_1_3_1","first-page":"762","article-title":"Pubert\u00e9 pr\u00e9coce avec tumeur du dienc\u00e9phale. 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