2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-TPRV6 Related Disorder in a Patient with Suspected Osteogenesis Imperfecta (OI)

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This case presentation discusses a 5-week-old female infant with suspected osteogenesis imperfecta (OI) who presented with respiratory distress and multiple rib fractures. The initial imaging indicated differential diagnoses of OI type 3 and hypophosphatasia. Laboratory evaluation showed normal alkaline phosphatase, ionized calcium, and other markers. Skeletal dysplasia sequencing panel revealed variants of uncertain significance (VUS) in MYO18B, SLCO2A1, and TRAF3IP1 genes. Exome sequencing identified a homozygous pathogenic variant in the TRPV6 gene, consistent with a diagnosis of transient neonatal hyperparathyroidism (TNHP). TNHP is an autosomal recessive condition caused by insufficient placental maternal-fetal calcium transport. The authors emphasize the importance of considering TNHP in the differential diagnosis of neonates presenting with fractures and suspicion of OI, especially with atypical x-ray findings. The study also suggests including the TPRV6 gene in current skeletal dysplasia panels and considering exome sequencing when panels are non-informative. Counseling considerations include discussing a recurrence risk of 25% and preventive measures such as maternal calcium supplementation during the third trimester. Prognostic considerations involve potential complete skeletal recovery and weaning off oxygen requirement. The authors acknowledge the family and the Face2Gene Skeletal Dysplasia Forum for their input, particularly Dr. Gen Nishimura.

Asset Subtitle

Presenting Author - Rana Aljaberi, MD; Co-Author - Rossana Sanchez, MD; Co-Author - marie-helene gagnon, MD;

Meta Tag

Bone/Joint Abnormalities

Counseling

Exome sequencing

Genetic Testing

Co-Author Rossana Sanchez, MD

Co-Author marie-helene gagnon, MD

Presenting Author Rana Aljaberi, MD

Keywords

osteogenesis imperfecta

respiratory distress

rib fractures

hypophosphatasia

alkaline phosphatase

ionized calcium

skeletal dysplasia sequencing panel

variants of uncertain significance

transient neonatal hyperparathyroidism

TRPV6 gene