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.

Chondrodysplasia punctata associated with maternal autoimmune diseases: expanding the spectrum from systemic lupus erythematosus (SLE) to mixed connective tissue disease (MCTD) and scleroderma report of eight cases.

Chondrodysplasia punctata (CDP) is etiologically a heterogeneous condition and has been associated with single gene disorders, chromosome abnormalities and teratogenic exposures. The first publication of the association between CDP and maternal autoimmune connective tissue disorder was by Curry et al. 1993]. Chondrodysplasia punctata associated with maternal collagen vascular disease. A new etiology? Presented at the David W. Smith Workshop on Morphogenesis and Malformations, Mont Tremblant, Quebec, August 1993] and subsequently, other cases have been reported. We report on eight cases of maternal collagen vascular disease associated with fetal CDP and included the cases reported by Curry et al. 1993. Chondrodysplasia punctata associated with maternal collagen vascular disease. A new etiology? Presented at the David W. Smith Workshop on Morphogenesis and Malformations, Mont Tremblant, Quebec, August 1993] and Costa et al. [1993]. Maternal systemic lupus erythematosis (SLE) and chondrodysplasia punctata in two infants. Coincidence or association? 1st Meeting of Bone Dysplasia Society, Chicago, June 1993] which were reported in an abstract form. We suggest that maternal autoimmune diseases should be part of the differential diagnosis and investigation in newborns/fetuses with CDP. Thus, in addition to cardiac evaluation, fetuses/newborn to mothers with autoimmune diseases should have fetal ultrasound/newborn examination and if indicated, X-rays, looking for absent/hypoplastic nasal bone, brachydactyly, shortened long bones and epiphyseal stippling.

Neonatal lupus syndrome: a case with chondrodysplasia punctata and other unusual manifestations.

We report a case of a newborn infant whose mother had systemic lupus erythematosus (SLE) diagnosed before pregnancy. The child had clinical manifestations of neonatal lupus as well as chondrodysplasia punctata and other findings that resemble the congenital anomalies associated with the use of oral anticoagulants, with no history of exposure. We speculate that the combined action of the different maternal autoantibodies may produce the whole spectrum of manifestations.

Neutrophyl function in children with chondrodystrophia calcificans congenita: evidence for defective chemotaxis.

Some neutrophil functions (superoxide anion production, bactericidal activity and chemotaxis) have been examined in four children with Chondrodystrophia Calcificans Congenita. Superoxide anion production and bactericidal activity were in the normal range, but a defect in cellular chemotaxis has been proved. This finding account for predisposition to infection which is frequently present in these patients, and may include this disease among those syndromes in which a deficiency of the immune system is associated with growth failure.