Phenotypic Expansion: Fetus With Cole-Carpenter Type 2 Presenting With Novel Neonatal Lethal Skeletal Dysplasia

We report a 28-year-old G2P0 at 24 weeks 5 days who presented for evaluation secondary to suspected skeletal dysplasia in her fetus. Fetal ultrasound imaging demonstrated foreshortened long bones by 9-10 weeks, multiple bowing deformities and fractures, 11 foreshortened paired ribs with fractures, decreased skull mineralization, frontal bossing, enlarged cavum septum pellucidi, and severe fetal growth restriction (< 2%). Findings were concerning for life limiting condition with thoracic circumference < 2.5%, femur length/abdominal circumference ratio of 0.13, and the thoracic circumference/abdominal circumference ratio of 0.77 and a palliative care path was pursued. Exome sequencing through chorionic villus sampling revealed two variants SEC24D, a maternally inherited likely pathogenic variant at c.3031_3040delinsC, and a variant of uncertain significance (VUS) at c.2676 + 5del. These variants, along with the clinical overlap in the fetus were likely causative of a diagnosis of Cole-carpenter syndrome type 2 (CLCRP2). Most publications of CLCRP2 report a fairly favorable prognosis. Concern for life limiting prenatal presentation has not been reported. We report a case of CLCRP2 that phenocopies perinatally lethal type OI and that resulted in early neonatal demise from respiratory compromise.