Variability versus heterogeneity in syndromal hypothalamic hamartoblastoma and related disorders: Review and delineation of the Cerebro-Acro-Visceral Early lethality (CAVE) multiplex syndrome
Corresponding Author
Dr. Alain Verloes
Centre for Human Genetics, Liège University, Belgium
Centre de Génétique, Pathologie B23, CHU Sart Tilman, (B)-4000 Liege, BelgiumSearch for more papers by this authorYves Gillerot
Centre for Human Genetics, Institute for Morphologic Pathology, Loverval, Belgium
Search for more papers by this authorJean-Paul Langhendries
Neonatal Intensive Care Unit, Clinique St Vincent, Rocourt, Belgium
Search for more papers by this authorJean-Pierre Fryns
Centre for Human Genetics, Leuven University, Belgium
Search for more papers by this authorLucien Koulischer
Centre for Human Genetics, Liège University, Belgium
Search for more papers by this authorCorresponding Author
Dr. Alain Verloes
Centre for Human Genetics, Liège University, Belgium
Centre de Génétique, Pathologie B23, CHU Sart Tilman, (B)-4000 Liege, BelgiumSearch for more papers by this authorYves Gillerot
Centre for Human Genetics, Institute for Morphologic Pathology, Loverval, Belgium
Search for more papers by this authorJean-Paul Langhendries
Neonatal Intensive Care Unit, Clinique St Vincent, Rocourt, Belgium
Search for more papers by this authorJean-Pierre Fryns
Centre for Human Genetics, Leuven University, Belgium
Search for more papers by this authorLucien Koulischer
Centre for Human Genetics, Liège University, Belgium
Search for more papers by this authorAbstract
We report on a case of neonatal hypothalamic hamartoblastoma with holoprosencephaly, Hirschsprung disease, and tetramelic postaxial polydactyly. Twenty-seven 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-Hall syndrome) and related diseases as Smith-Lemli-Opitz type II, holoprosencephaly-polydactyly, 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-Hall rather than another MCA syndrome, and, ultimately, the existence of Pallister-Hall 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. “Cerebro-Acro-Visceral Early lethality multiplex syndrome” is suggested to encompass all the ambiguous cases. Within this complex, an operative classification key is proposed. © 1992 Wiley-Liss, Inc.
References
- Anyane-Yeboa K, Collins M, Kupsky W, Maidman J, Malin J, Yeh M (1987) Hydrolethalus syndrome: Further clinicopathological delineation. Am J Med Genet 26: 899–907.
- Bach C, Bitan A, Jolly G, Grange G (1969) Puberté précoce avec tumeur du diencéphale. Association à un syndrome de Dandy-Walker et à des anomalies dysraphiques. Ann Pediatr 16: 762–767.
- Bertelotti M (1914–1915) Polydactylie et tératome hypophysaire. Nouvelle Iconographie de la Salpétrière Tôme 27.
- Brouwer B (1950) Ueber die Pathologie des Hypothalamus. Schweiz Arch Neurol Psychia 65: 35–51.
- Clarren SK, Alvord EC, Hall JG (1980) Congenital hypothalamic hamartoblastoma, hypopituitarism, imperforate anus and postaxial polydactyly–a new syndrome? Part II: Neuropathological considerations. Am J Med Genet 7: 75–83.
- Cohen MM Jr (1989) Perspective on holoprosencephaly: Part I. Epidemiology, genetics and syndromology. Teratology 40: 211–235.
- Cohen MM Jr, Gorlin RJ (1991) Pseudo-Trisomy 13 syndrome. Am J Med Genet 39: 332–335.
- Culler FL, Jones KL (1984) Hypopituitarism in association with hypothalamic hamartoblastoma. Pediatrics 104: 881–884.
- Curry CL, Carey JC, Holland JS, Chopra D, Fineman R, Golabi M, Sherman S, Pagon RA, Allanson J, Shulman S, Barr M, McGravey V, Dabiri C, Schimke N, Ives E, Hall BD (1987) Smith-Lemli-Opitz syndrome–type II: Multiple congenital anomalies with male pseudohermaphroditism and frequent early lethality. Am J Med Genet 26: 45–57.
- Donnai D, Burn J, Hughes H (1987) Smith-Lemli-Opitz syndromes: Do they include the Pallister-Hall syndrome? Am J Med Genet 28: 741–743.
- Gitlin G, Behar AJ (1960) Meningeal angiomatosis, arhinencephaly, agenesis of corpus callosum and large hamartoma of the brain, with neoplasias, in infant with bilateral proboscis. Acta Anat (Basel) 41: 56–79.
- Gorlin R, Cohen MM Jr, Levin LS (1990) “ Syndromes of Head and Neck.” Oxford: Oxford University Press.
- Graham JM Jr, Saunders R, Fratkin J, Spiegel P, Harris M, Klain RZ (1986) A cluster of Pallister-Hall syndrome cases (congenital hypothalamic hamartoblastoma syndrome). Am J Med Genet [suppl 2]: 53–63.
- Greenberg F, Gresik MV, Carpenter RJ, Law SW, Hoffman LP, Ledbetter DH (1987) The Gardner-Silengo-Wachtel or genitopalatocardiac syndrome: Male pseudohermaphroditism with micrognathia, cleft palate and conotruncal cardiac defect. Am J Med Genet 26: 59–64.
- Hall JG, Pallister PD, Clarren SK, Beckwith JB, Wiglesworth FW, Fraser FC, Cho S, Benke PJ, Reed SD (1980) Congenital hypothalamic hamartoblastoma, hypopituitarism, imperforate anus and postaxial polydactyly—a new syndrome? - Part I: Clinical, causal and pathogenic considerations. Am J Med Genet 7: 47–74.
- Hennekam RCM, Beemer FA, Van Merrienboer F, Van Ketel BA, Kramer PPG (1986) Congenital hypothalamic hamartoblastoma associated with severe midline defect: A developmental field defect. Report of a case. Am J Med Genet [Suppl. 2]: 45–52.
- Huff DS, Fernandes M (1982) Two cases of congenital hypothalamic hamartoblastoma, polydactyly and other congenital anomalies (Pallister-Hall syndrome). N Engl J Med 306: 430–431.
- Iafolla K, Fratkin JD, Spiegel PK, Cohen MM Jr, Graham JM (1989) Case report and delineation of the congenital hypothalamic hamartoblastoma syndrome (Pallister-Hall syndrome). Am J Med Genet 33: 489–499.
- Kurnit DM, Layton WM, Matthyse S (1987) Genetics, chance and morphogenesis. Am J Hum Genet 41: 979–995.
- Le Merrer M, Briard ML, Girard S, Mulliez N, Moraine C, Imbert MC (1988) Lethal acrodysgenital dwarfism: A severe lethal condition resembling Smith-Lemli-Opitz dwarfism. J Med Genet 25: 88–95.
- Mattéi JF, Aymé S (1983) Syndrome of polydactyly, cleft lip, lingual hamartomas, renal hypoplasia, hearing loss and psychomotor retardation. Variant of the Mohr syndrome or a new syndrome? J Med Genet 20: 433–435.
- Marcuse PM, Burger RA, Salton GW (1953) Hamartoma of the hypothalamus: Report of two new cases with associated developmental defects. J Pediatr 43: 301–308.
- Münke M, McDonald DM, Cronister A, Stewart JM, Gorlin RJ, Zackai EH (1990) Orafacial-digital syndrome type VI (Varadi syndrome): Further clinical delineation. Am J Med Genet 35: 360–369.
- Opitz JM, Gilbert EF (1982) CNS anomalies and the midline as a “developmental field”. Am J Med Genet 12: 443–445.
- Opitz JM, Lowry RB (1987) Lincoln vs Douglass again; comments on the papers by Curry et al., Greenberg et al. and Belmont et al. Am J Med Genet 26: 69–72.
- Pallister PD, Hecht F, Herrmann J (1989) Three additional cases of the congenital hypothalamic “hamartoblastoma” (Pallister-Hall) syndrome. Am J Med Genet 33: 500–501.
- Ramaekers PR, Legius E, Verloes A, Gillerot Y, Vandenberghe K, Fryns JP (1990) Holoprosencephaly and postaxial polydactyly with normal chromosomes. Another observation of a new malformation syndrome. Eur J Obstet Gynecol Reprod Biol 36: 161–165.
-
Rozen Z,
Gitlin G
(1959)
Bilateral nasal proboscis.
Arch Otolaryng
70:
545–550.
10.1001/archotol.1959.00730040557002 Google Scholar
- Rutledge JC, Friedman JM, Harrod MJE, Currarino G, Wright CG, Pinckney L, Chen H (1984) A “new” multiple congenital anomaly syndrome: Joint contractures, cerebellar hypoplasia, renal hypoplasia, urogenital anomalies, tongue cysts, shortness of limbs, eye abnormalities, defect in the heart, gallbladder agenesis and ear malformations. Am J Med Genet 19: 174–175.
- Salonen R, Herva R (1990) The hydrolethalus syndrome. J Med Genet 27: 756–759.
- Stotijn CPJ, Nauta WJH (1950) Precocious puberty and tumour of the hypothalamus, with report of a case and consideration of hypothalamo-hypophyseal connections. J Neur Ment Dis 111: 207–224.
- Varadi V, Szabo L, Papp Z (1980) Syndrome of polydactyly, cleft lip/palate or lingual lump and psychomotor retardation in endogamic gypsies. J Med Genet 17: 199–122.
- Verloes A, Aymé S, Gambarelli D, Gonzales M, Le Merrer M, Mulliez N, Philip N, Roume J (1991) Holoprosencephaly-polydactyly (“pseudo-trisomy 13”) syndrome: A syndrome with features of hydrolethalus and Smith-Lemli-Opitz syndromes. A collaborative multicentric study. J Med Genet 28: 297–303.
- Warkany J, Lemire RJ, Cohen MM Jr (1981) “ Mental Retardation and Congenital Malformations of the Central Nervous System.” Chicago: Year Book Medical Publishers, p 294.
- Winter WE, Rosenbloom AL, Maclaren NK, Mickle JP (1982) Solitary central maxillary incisor associated with precocious puberty and hypothalamic hamartoma. J Pediatr 10: 965–967.
- Young ID, Madders DJ (1987) Unknown syndrome: Holoprosencephaly, congenital heart defects and polydactyly. J Med Genet 24: 714–716.
References
- Encha-Razavi F, Larroche JC, Roume J, Migna G, Delezoide AL, Gonzales M, Mulliez N (1992) Congenital hypothalamic hamartoma syndrome, nosological discussion and minimum diagnostic criteria of a possible familial form. Am J Med Genet 42: 44–50.
- Finnigan DP, Clarren SK, Hass JE (1992) Extendiong Pallister-Hall syndrome to include other central nervous system malformations. Am J Med Genet 40: 395–400.
- Golabi M, Kuller J, Cox K, Keilman K, Schonberg S (1991) Pallister-Hall syndrome associated with an unbalanced chromosome translocation. Am J Hum Genet 49 (suppl.): 137.
- Greenhaw G, Orlander P, Langford L, Horton W (1991) Longterm survival in Pallister-Hall syndrome. Am J Hum Genet 49 (suppl.): 138.
- Hennekam RCM, Van Noort G, de la Fuente AA (1991) Familial holopresencephaly, heart defects and polydactylt. Am J Med Genet 41: 258–262.
- Hingorani SR, Pagon RA, Shepard TH, Kapur RP (1991) Twin fetuses with abnomalities that overlap with three midline malformation complexes. Am J Med Genet 41: 230–235.
- Krassikoff N, Konick L, Gilbert EF (1987) The hydrolethalus syndrome. New York: Alan R. Liss. Birth Defects: OAS 23: 411–429.
- Muenke M, Ruchelli ED, Rorke LB, McDonald-McGinn DM, Orlow MK, Isaacs A, Craparo FJ, Dunn LK, Zackai EH (1991) On lumping and splitting: a fetus with clinical findings of the oral-facial-digital syndrome type VI, the hydrolethalus syndrome and the Pallister-Hall syndrome. Am J Med Genet 41: 548–556.
- Nurbhai MA, Tomlinson BE, Lorigan-Forsythe B (1985) Infantile hypothalmic hamartoma with multiple congenital abnormalities. Neuropathol Appl Neurobiol 11: 61–70.
