PMID- 34169121
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220424
IS  - 2352-1872 (Print)
IS  - 2352-1872 (Electronic)
IS  - 2352-1872 (Linking)
VI  - 15
DP  - 2021 Dec
TI  - 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.
PG  - 101097
LID - 10.1016/j.bonr.2021.101097 [doi]
LID - 101097
AB  - BACKGROUND: Loss-of-function variants in the calcium-sensing receptor (CASR) gene 
      are known to be involved in a clinical spectrum ranging from asymptomatic 
      familial hypocalciuric hypercalcemia (FHH) to neonatal severe hyperparathyroidism 
      (NSHPT). Homozygous or compound heterozygous variants are usually responsible for 
      severe neonatal forms, whereas heterozygous variants cause benign forms. One 
      recurrent pathogenic variant, p.Arg185Gln, has been reported in both forms, in a 
      heterozygous state. This variant can be a de novo occurrence or can be inherited 
      from a father with FHH.NSHPT leads to global hypotonia, failure to thrive, 
      typical X-ray anomalies (diffuse demineralization, fractures, metaphyseal 
      irregularities), and acute respiratory distress which can be fatal. Phosphocalcic 
      markers show severe hypercalcemia, abnormal urinary calcium resorption, and 
      hyperparathyroidism as major signs.Classical treatment involves calcium 
      restriction, hyperhydration, and bisphosphonates. Unfortunately, the disease 
      often leads to parathyroidectomy. Recently, calcimimetics have been used with 
      variable efficacy. Efficacy in NSHPT seems to be particularly dependent on CASR 
      genotype. CASE PRESENTATION: We describe the antenatal presentation of a male 
      with short ribs, initially suspected having skeletal ciliopathy. At birth, he 
      presented with NSHPT linked to the pathogenic heterozygous CASR variant, 
      Arg185Gln, inherited from his father who had FHH. Postnatal therapy with 
      cinacalcet was successful. DISCUSSION: An exhaustive literature review permits a 
      comparison with all reported cases of Arg185Gln and to hypothesize that 
      cinacalcet efficacy depends on CASR genotype. This confirms the importance of 
      pedigree and parental history in antenatal short rib presentation and questions 
      the feasibility of phosphocalcic exploration during pregnancy or prenatal CASR 
      gene sequencing in the presence of specific clinical signs. It could in fact 
      enable early calcimimetic treatment which might be effective in the CASR variant 
      Arg185Gln.
CI  - (c) 2021 The Author(s).
FAU - Aubert-Mucca, Marion
AU  - Aubert-Mucca M
AD  - Department of Medical Genetics, Toulouse University Hospital, Toulouse, France.
AD  - Endocrine, Bone Diseases, and Genetics Unit, Reference Center for Rare Diseases 
      of Calcium and Phosphate Metabolism, ERN BOND, OSCAR Network, Children's 
      Hospital, Toulouse University Hospital, Toulouse, France.
FAU - Dubucs, Charlotte
AU  - Dubucs C
AD  - Department of Medical Genetics, Toulouse University Hospital, Toulouse, France.
FAU - Groussolles, Marion
AU  - Groussolles M
AD  - Department of Obstetrics and Gynecology, Toulouse University Hospital, Toulouse, 
      France.
FAU - Vial, Julie
AU  - Vial J
AD  - Department of Radiology, Children's University Hospital, Toulouse, France.
FAU - Le Guillou, Edouard
AU  - Le Guillou E
AD  - Department of Genetic and Molecular Biology, Cochin Hospital, AP-HP 
      Centre-Universite de Paris, Paris, France.
FAU - Porquet-Bordes, Valerie
AU  - Porquet-Bordes V
AD  - Endocrine, Bone Diseases, and Genetics Unit, Reference Center for Rare Diseases 
      of Calcium and Phosphate Metabolism, ERN BOND, OSCAR Network, Children's 
      Hospital, Toulouse University Hospital, Toulouse, France.
FAU - Pasmant, Eric
AU  - Pasmant E
AD  - Department of Genetic and Molecular Biology, Cochin Hospital, AP-HP 
      Centre-Universite de Paris, Paris, France.
FAU - Salles, Jean-Pierre
AU  - Salles JP
AD  - Endocrine, Bone Diseases, and Genetics Unit, Reference Center for Rare Diseases 
      of Calcium and Phosphate Metabolism, ERN BOND, OSCAR Network, Children's 
      Hospital, Toulouse University Hospital, Toulouse, France.
FAU - Edouard, Thomas
AU  - Edouard T
AD  - Endocrine, Bone Diseases, and Genetics Unit, Reference Center for Rare Diseases 
      of Calcium and Phosphate Metabolism, ERN BOND, OSCAR Network, Children's 
      Hospital, Toulouse University Hospital, Toulouse, France.
LA  - eng
PT  - Case Reports
DEP - 20210609
PL  - United States
TA  - Bone Rep
JT  - Bone reports
JID - 101646176
PMC - PMC8209172
OTO - NOTNLM
OT  - Calcimimetics
OT  - Calcium-sensing receptor
OT  - Familial hypocalciuric hypercalcemia
OT  - Neonatal severe hyperparathyroidism
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2021/06/26 06:00
MHDA- 2021/06/26 06:01
PMCR- 2021/06/09
CRDT- 2021/06/25 06:55
PHST- 2021/03/06 00:00 [received]
PHST- 2021/05/25 00:00 [revised]
PHST- 2021/06/01 00:00 [accepted]
PHST- 2021/06/25 06:55 [entrez]
PHST- 2021/06/26 06:00 [pubmed]
PHST- 2021/06/26 06:01 [medline]
PHST- 2021/06/09 00:00 [pmc-release]
AID - S2352-1872(21)00353-3 [pii]
AID - 101097 [pii]
AID - 10.1016/j.bonr.2021.101097 [doi]
PST - epublish
SO  - Bone Rep. 2021 Jun 9;15:101097. doi: 10.1016/j.bonr.2021.101097. eCollection 2021 
      Dec.