Prenatal bone abnormalities in three cases of familial hypocalciuric hypercalcemia

• Published in: Prenatal diagnosis Vol. 42; no. 5; pp. 583 - 588
• Main Authors: Frerot, Alice, Baudouin, Véronique, Rideau‐Batista, Aline, Couderc, Anne, Garel, Catherine, Soltane, Samia, Colella, Marina, Vargas‐Poussou, Rosa, Hureaux, Marguerite
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-05-2022; Wiley
• Subjects: Abnormalities; Anomalies; Birth; Bones; Calcium; Calcium metabolism; Calcium phosphates; Calcium-sensing receptors; Dental enamel; Diagnosis; Differential diagnosis; Etiology; Female; Genetic counseling; Genetic screening; Genetics; Humans; Hypercalcemia; Hypercalcemia - complications; Hypercalcemia - congenital; Hypercalcemia - diagnosis; Hypercalcemia - genetics; Hyperparathyroidism; Hyperparathyroidism - complications; Hypocalciuria; Infant, Newborn; Kidney Diseases; Kidney Diseases - complications; Life Sciences; Male; Mineralization; Mutation; Neonates; Pregnancy; Prenatal diagnosis; Receptors, Calcium-Sensing; Receptors, Calcium-Sensing - genetics; Ultrasonic imaging; Ultrasound
• ISSN: 0197-3851; 1097-0223
• DOI: 10.1002/pd.6134

Introduction
Prenatal diagnosis of bone and mineralization anomalies is associated with a wide range of etiologies and prognoses. The improvement of antenatal ultrasound combined with the development of molecular diagnosis in genetics has transformed antenatal medicine into a challenging discipline. Of the various known causes of bone abnormalities and hypomineralization, calcium and phosphate metabolism disorders are exceptional. An accurate diagnosis is crucial for providing appropriate genetic counseling and medical follow‐up after birth.
Case
We report on three siblings with severe bone abnormalities diagnosed during the second trimester ultrasound of pregnancy. Postnatal follow‐up showed transitory hyperparathyroidism, with hypercalcemia and hypocalciuria.
Methods
Sanger sequencing performed after birth in the three newborns revealed a monoallelic pathogenic variant in the CASR gene, encoding the calcium sensing receptor, confirming the diagnosis of familial hypocalciuric hypercalcemia, paternally inherited. Postnatal evolution was favorable after treatment with a calcimimetic agent.
Conclusions
Previously, prenatal bone abnormalities caused by familial hypocalciuric hypercalcemia had only been described in one patient. This entity should be considered as differential diagnosis of bones abnormalities. Knowing about this unusual etiology is important to guide the diagnosis, the prenatal counseling and to improve medical management.
Highlights
What is already know?
Familial hypocalciuric hypercalcemia type 1 (FHH1) is a genetic disorder, caused mainly by heterozygous mutations in the CASR gene. It associates hypercalcemia, normal PTH value, and normo‐ or hypocalciuria. Some children may present with bone abnormalities and early hyperparathyroidism, resolving gradually.
What does this study add?
This article presents three cases of prenatal bone abnormalities due to postnatally genetically confirmed FHH that resolved within the first years of life. This condition should be considered as a differential diagnosis in antenatal bone abnormalities.