The etiology and pathogenesis of this syndrome has not yet been established and are under study. There are assumptions that the disease is hereditary and may be due to various genetic anomalies, although the gene responsible for intrauterine development disorders and the type of its transmission has not yet been determined (a hypothesis about mutations in the BIPBL gene (HSA 5p13.1) encoding delangin is put forward).
Mutations in the genes that encode two other proteins involved in the cohesion of sister chromatids, SMC1A and SMC3, were reported in 5% and 1% of patients with Cornelia de Lange syndrome, respectively.
Analysis of the samples of this disease suggests that the inheritance of a mutant gene in this case is not characterized by a primitive transfer. Probably, over time, an improved cytogenetic study will be able to identify pathology at the chromosomal level.
Most of the studied episodes of the Cornelia de Lange syndrome are single, and there were usually no changes in the chromosome set of patients, although anomalies were occasionally detected - more often there was fragmentary trisomy over the long arm of chromosome 3 and chromosome 1, and chromosome 9 had the shape of a ring.
There are also known cases of disease of members of one family, in the analysis of which, an assumption is made about the autosomal recessive way of transferring the gene that provokes this pathology.
Nevertheless, in the manifestations of the syndrome, members of one family do not have complete or partial underdevelopment of the limbs, as in single cases. Based on this, a hypothesis is advanced about the differences in the causes of family and single cases of Cornelia de Lange syndrome.
The influence of the father's age on the incidence of a child with this disease is more than controversial, so it is still unclear whether this syndrome can trigger single autosomal dominant transformations of the genotype.