American Journal of Medical Genetics 118A:198 (2003)
Correspondence
Another Explanation for Familial Cornelia deLange Syndrome
To The Editor:
Russell et al. [2001] provide a most useful review ofthe small number of families on record with more thanone instance ofCornelia deLange syndromeandpresentalso a case of their own. They go through a checklist ofpossible modes of inheritance: dominant (includinggonadal mosaicism), recessive, mentioning X-linkage,and mitochondrial inheritance, and with a nod to thepossibility of an imprinting effect. In the end, theycome out in favor of autosomal dominant, with mostcases reflecting a fresh mutation.
One other mode of inheritance is worth mentioning,and that is ‘‘emergenesis.’’ As Li [1987] reviewed thisconcept, emergenesis can be thought of as a polygenicmechanism in which the combination of genotypes at anumber of loci may combine to produce a rare constella-tion that can lead to a particular phenotype. He quotesLykken, who introduced the concept, as referring to‘‘every component being a keystone element’’ in thisparticular collection of genotypes. (While Lykken hadused emergenesis as an explanation for genius thatoccasionally pops up in a family, such as the mathema-tician Gauss, the same concept could, in principle, applyin the opposite direction.) Even the popular press refersto the concept: in an article in Time magazine (6 May2002) on the genetics of autism, it is discussed that thebasis might lie in ‘‘garden-variety variants of normalgenes that cause problems onlywhen they combinewithcertain other genes.’’
I recall a article, from 20 or more years ago, I thinkfrom Italy, but which unfortunately I cannot now re-discover, that describedmicrosigns of Cornelia deLangesyndrome in relatives: as though the child’s conditionwas the sum of contributions from different lines in thefamily, which became exaggerated when all were com-bined together in the one individual. Many geneticistswould have seen children with a referring diagnosis ofCornelia de Lange syndrome, who in fact do not makethe cut, but in whom, nevertheless, the picture isreminiscent. Could such patients represent a less com-plete form of emergenesis?
Russell et al. may well be right, and amongst the sup-posed heterogeneity, a dominant genemay be the majorplayer. But emergenesis does deserve consideration.
REFERENCES
Li CC. 1987. A genetical model for emergenesis: In memory of Laurence H.Snyder, 1901–86. Am J Hum Genet 41:517–523.
Russell KL, Ming JE, Patel K, Jukofsky L, Magnusson M, Krantz ID. 2001.Dominant paternal transmission of Cornelia de Lange syndrome: A newcase and review of 25 previously reported familial recurrences. AmJ Med Genet 104:267–276.
R.J.M. Gardner*Genetic Health Services VictoriaRoyal Children’s HospitalMelbourne, Australia
*Correspondence to: R.J.M. Gardner, Genetic Health ServicesVictoria, Royal Children’s Hospital, Melbourne, Vic. 3052,Australia. E-mail: [email protected]
Received 4 June 2002; Accepted 9 July 2002
DOI 10.1002/ajmg.a.10900
� 2003 Wiley-Liss, Inc.
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