Antenatal Phenotype of Desbuquois Dysplasia

Abstract

Desbuquois dysplasia (DBQD) is an uncommon, autosomal recessive disorder with multiple joint dislocations. It is caused by pathogenic variants in CANT1 (calcium-activated nucleotidase 1) [NM_001159773.2]. This study adds to the scant data of nine reported antenatal phenotypes of DBQD. The present paper describes two unrelated consanguineous families with antenatal features of lethal skeletal dysplasia. The defining radiological changes were identified in only one patient who presented in the late second and third trimesters. Solo exome sequencing was performed and two previously reported homozygous variants c.896C>T (p.Pro299Leu) in patient 1 and c.902_906dup (p.Ser303fs*20) in patient 2 were identified. This study highlights the fetal presentations in DBQD and adds to its phenotypic spectrum. A complete clinical workup, including fetal autopsy and radiographs is essential to confirm the diagnosis of lethal skeletal dysplasia. Molecular diagnosis remains the diagnostic modality to define the causative variant. A definitive diagnosis is essential to inform management and offer reproductive care.

Keywords: CANT1 gene; Cystic hygroma; Desbuquois dysplasia; Fetal hydrops; Fetal phenotype; Lethal skeletal dysplasia.