Prenatal features and neonatal management of severe hyperparathyroidism caused by the heterozygous inactivating calcium-sensing receptor variant, Arg185Gln: A case report and review of the literature

• DOI: 10.1016/j.bonr.2021.101097
• Publication Date: 2021-06-09T08:18:07Z
• Authors: Marion Aubert-Mucca; Charlotte Dubucs; Marion Groussolles; Julie Vial; Edouard Le Guillou; Valerie Porquet-B...; Eric Pasmant; Jean-Pierre Salles; Thomas Edouard
• Keywords: Cinacalcet; Failure to Thrive; Compound heterozygosity

Loss-of-function variants in the calcium-sensing receptor (CASR) gene are known to be involved a clinical spectrum ranging from asymptomatic familial hypocalciuric hypercalcemia (FHH) neonatal severe hyperparathyroidism (NSHPT). Homozygous or compound heterozygous usually responsible for forms, whereas cause benign forms. One recurrent pathogenic variant, p.Arg185Gln, has been reported both state. This variant can de novo occurrence inherited father with FHH.NSHPT leads global hypotonia, failure thrive, typical X-ray anomalies (diffuse demineralization, fractures, metaphyseal irregularities), and acute respiratory distress which fatal. Phosphocalcic markers show hypercalcemia, abnormal urinary calcium resorption, as major signs.Classical treatment involves restriction, hyperhydration, bisphosphonates. Unfortunately, disease often parathyroidectomy. Recently, calcimimetics have used variable efficacy. Efficacy NSHPT seems particularly dependent on CASR genotype.We describe antenatal presentation of male short ribs, initially suspected having skeletal ciliopathy. At birth, he presented linked Arg185Gln, his who had FHH. Postnatal therapy cinacalcet was successful.An exhaustive literature review permits comparison all cases Arg185Gln hypothesize that efficacy depends genotype. confirms importance pedigree parental history rib questions feasibility phosphocalcic exploration during pregnancy prenatal sequencing presence specific signs. It could fact enable early calcimimetic might effective Arg185Gln.