New Fetal Case of Blomstrand Chondrodysplasia and Review of the Literature

Abstract

Blomstrand chondrodysplasia (BOCD) is a very rare autosomal recessive lethal skeletal dysplasia characterized by advanced skeletal ossification, markedly short limbs, hydrops fetalis and typical facial dysmorphism comprising proptosis, maxillary hypoplasia, micrognathia and a large-protruding tongue. Accompanying non-skeletal features include preductal aortic coarctation, gut malrotation, and hemosiderosis of the liver. Radiological evaluation is crucial for clinical diagnosis. Increased bone density, very short tubular bones with wide ends, short and thickened ribs and clavicles are typical findings. Only 14 cases have been reported previously. Inactivating mutations of the parathyroid hormon receptor-1 gene (PTHR1) are associated with BOCD. BOCD is allelic with Eiken syndrome, and Jansen type metaphyseal chondrodysplasia, presumably caused by truncating mutations in the C-terminal cytoplasmic tail, and activating mutations, respectively.Here, we present a new case with Blomstrand chondrodysplasia with a novel mutation in PTHR1.The fetus was the third-born to consanguineous parents. At the 21stgestational week, ultrasound examination showed proptosis, short nose, severe micrognathia, tetramicromelia, and narrow thorax. Fetal karyotype and chromosomal array revealed normal results. Parents chose to terminate the pregnancy due to expected lethal course related with the phenotype. Postmortem clinical examinationshowed broad forehead, proptosis, midface hypoplasia, microstomia, submucosal cleft palate, severe micrognathia, generalized oedema, and narrow thorax, and very short limbs with severe brachydactyly. The radiological findingswere short-dense-bowed tubular bones with flared wide metaphyseal ends, constricted diaphyses, split-ends of humeri and femora, short-thick ribs and clavicles, leading to the diagnosis of BOCD. Sanger sequencing ofthe PTH1R gene revealed a homozygous change, c.1309T>C, leading to p.Trp437Arg. This novel mutation was predicted to be damaging by in silico analyses.New BOCD case will be discussed in view of molecular findings,and a review of the literature will be presented.