Maternal mixed connective tissue disease and offspring with chondrodysplasia punctata.

Objectives: To describe the case of a mother with mixed connective tissue disease (MCTD) whose male and female offspring from 2 successive pregnancies had chondrodysplasia punctata (CDP) in the absence of identifiable biochemical or genetic abnormalities or teratogen exposure.

Methods: Description of a male and female offspring from a mother with MCTD harboring high-titer anti-ribonucleoprotein (RNP) antibodies. Maternal autoantibody assays were performed employing quantitative multiplex suspension arrays and flow cytometry, and autoantibody titer and pattern were determined by indirect immunofluorescence. Assays of phytanic acid, plasmalogen, and very long-chain fatty acids were performed employing commercially available reagents. Chromosomal analysis was performed on both offspring employing standard cytogenetic analysis. Review of the relevant literature was performed (PubMed search 1966 through July 2008).

Results: Two children with CDP born to a mother with MCTD who harbored anti-RNP autoantibodies at high titer are described. Genetic and chromosomal studies and biochemical analysis of peroxisome function and very long-chain fatty acids excluded known biochemical or genetic defects or mutations as the cause of CDP in these children. Furthermore, detailed review of the clinical history failed to disclose any evidence of maternal teratogen exposure during the 2 pregnancies.

Conclusions: Maternal MCTD is the most likely explanation for the occurrence of CDP in the 2 children reported here. Review of previously published cases of CDP associated with autoimmune disease suggests that placental crossing of maternal autoantibodies during pregnancy specifically affecting the normal development of fetal growth plates is responsible for CDP in the offspring in these cases.