Three unrelated infants presented with radiographic punctate calcifications, nasal hypoplasia, and abnormalities of the spine. Additional anomalies included cupped ears in 2 patients and one each with Dandy-Walker malformation with hydrocephaly, congenital cataracts, and peripheral pulmonary artery stenosis. The mothers of these 3 patients had chronic conditions associated with intestinal malabsorption requiring total parenteral nutrition for varying periods of time. The underlying causes of malabsorption were celiac disease, short bowel syndrome secondary to surgical resection, and jejuno-ileal bypass, respectively. Bleeding diathesis occurred in one mother requiring vitamin K supplementation during the second and third trimesters of pregnancy. We speculate that the chondrodysplasia punctata and other abnormalities in these children were caused by an acquired maternal vitamin K deficiency manifested during early pregnancy. However, the involvement of other vitamin deficiencies cannot be excluded. Thus, vitamin K deficiency of the embryo secondary to maternal malabsorption appears to be a third vitamin K-related mechanism leading to chondrodysplasia punctata in addition to warfarin embryopathy and epoxide reductase deficiency (pseudo-warfarin embryopathy).

Three unrelated infants presented with radiographic punctate calcifications, nasal hypoplasia, and abnormalities of the spine. Additional anomalies included cupped ears in 2 patients and one each with Dandy-Walker malformation with hydrocephaly, congenital cataracts, and peripheral pulmonary artery stenosis. The mothers of these 3 patients had chronic conditions associated with intestinal malabsorption requiring total parenteral nutrition for varying periods of time. The underlying causes of malabsorption were celiac disease, short bowel syndrome secondary to surgical resection, and jejuno-ileal bypass, respectively. Bleeding diathesis occurred in one mother requiring vitamin K supplementation during the second and third trimesters of pregnancy. We speculate that the chondrodysplasia punctata and other abnormalities in these children were caused by an acquired maternal vitamin K deficiency manifested during early pregnancy. However, the involvement of other vitamin deficiencies cannot be excluded. Thus, vitamin K deficiency of the embryo secondary to maternal malabsorption appears to be a third vitamin K-related mechanism leading to chondrodysplasia punctata in addition to warfarin embryopathy and epoxide reductase deficiency (pseudo-warfarin embryopathy).

We describe two unrelated children with Kniest dysplasia, a severe autosomal dominant form of chondrodysplastic dwarfism associated with cleft palate, progressive arthropathy, myopia and retinal detachment. In the first patient the disorder was caused by a 28 base pair exon 12/intron 12 deletion in the gene coding for type II collagen. Her mother had mild abnormalities of the vertebral bodies and long bones compatible with abnormalities seen in Stickler arthro-ophthalmopathy. The second child had a transition of AG to GG at the 3' splice site of intron 20 of the COL2A1 gene. Her father had premature polvarthrosis interpreted as a sequela of mild spondyloepiphyseal dysplasia. Molecular studies revealed that the mother of the first and the father of the second child each had somatic mosaicism of the same mutation as their children. Heterozygous mutations of the gene coding for type II collagen can cause Kniest dysplasia, and somatic mosaicism for the same mutations can result in the Stickler phenotype or in mild spondyloepiphyseal dysplasia leading to premature polyarthrosis.

We describe 7 patients with a new form of chondrodysplasia punctata. Its principal clinical manifestations are flat midface and nose, short limbs, and otherwise normal development. Consistent radiologic manifestations in the newborn infant are discrete calcific stippling, coronal clefts of vertebral bodies, short tibiae, and shortness of the 2nd and 3rd metacarpal bones. Radiologic findings in the older child include shortness of tibiae and the 3rd and 4th metacarpals.

In three sibs of Jordanian descent a unique type of severe spondylo‐meta‐epiphyseal dysplasia results in extreme disproportionate dwarfism. They have a distinct facial appearance with hypotelorism, prognathia, and hypodontia. The limbs are short and the hands and feet stubby. Radiologically, the irregular end plates of the vertebral bodies, the very small and late appearing epiphyseal ossification centres, and the hypoplastic acetabular roofs are most impressive. Histopathologic studies of the growth plate demonstrate characteristic findings with fingerprint‐like inclusion bodies in the hypertrophic chondrocytes. This seems to be a distinct, autosomal recessive skeletal dysplasia. © 1996 Wiley‐Liss, Inc.