269: Chondrodysplasia punctata associated with maternal hyperemesis gravidarum: A variable and potentially preventable phenotype

Chondrodysplasia punctata (CDP) is a disorder characterized by early and inappropriate calcification within growing cartilage. CDP is seen in a genetically heterogeneous group of disorders, some of which involve the vitamin K pathway. Several maternal conditions have also been associated with the CDP phenotype in infants. We report three unrelated patients with variable skeletal features of CDP in whom maternal pregnancy history was suggestive of vitamin K deficiency due to hyperemesis gravidarum (HG). We suggest vitamin K supplementation early in the course of HG in order to prevent this clinically variable but potentially fatal condition in infants. Retrospective review of patients with CDP seen at our institution from January 2013 through June 2017 was performed. We identified three African-American female neonates with CDP in whom all biochemical and gene testing was negative. In all three, severe maternal hyperemesis gravidarum was noted during the first trimester. We reviewed the pregnancy history and postnatal course of all three babies, including biochemical and genetic test results as well as findings on radiographic skeletal survey, CT, and MRI when performed. All imaging findings were reviewed by an experienced pediatric radiologist. Skeletal survey in Patient 1 showed nasal flattening, brachytelephalangy of hands and feet, numerous spinal and epiphyseal puncta. CT and MRI showed severe nasal aperture stenosis, critical cervical spinal stenosis, and myelomalacia of the upper cervical cord. She expired at 3.5 months of age. Patient 2 had nasal flattening and additional features of congenital heart disease. Skeletal survey showed numerous epiphyseal and paraspinal puncta, as well as brachytelephalangy. CT and MRI demonstrated moderate upper cervical spinal canal stenosis, nasal aperture stenosis, and bilateral grey matter heterotopias. Skeletal survey in Patient 3 showed nasal flattening, numerous epiphyseal and paraspinal puncta, as well as brachytelephalangy. CT and MRI are pending. CDP may be seen in infants of mothers with HG, which can result in maternal-fetal vitamin K deficiency. Vitamin K deficiency is hypothesized to cause CDP when it occurs between 6-9 weeks gestation. This CDP phenotype may be preventable with maternal vitamin K supplementation early in the course of HG.View Large Image Figure ViewerDownload Hi-res image Download (PPT)