A Rare PKHD1 Frameshift Variant Identified in a Prenatally Diagnosed ARPKD Case From a Consanguineous Jordanian Family.

INTRODUCTION: Polycystic kidney disease (PKD) is a condition that encompasses the development of multiple benign cysts in the kidneys and other organs. Hereditary PKD can be classified as autosomal dominant polycystic kidney disease (ADPKD) or autosomal recessive polycystic disease (ARPKD). These two forms differ primarily in their age of onset and clinical presentation. ADPKD is usually diagnosed during young adulthood, whereas ARPKD presents a wide range of clinical manifestations with approximately one-third of patients presenting before the first year of life, one-third between 1 and 20 years of age, and the remaining one-third after 20 years of age. ARPKD represents the severe form, typically presenting in infancy with significant renal and hepatic involvement. Hereditary and congenital forms are known to be caused by certain genetic defects associated with dysfunction of the primary cilia in the tubular epithelium. To the best of our knowledge, no similar cases have been reported in Jordan or neighboring countries. CASE PRESENTATION: We report a case of ARPKD in one fetus of a twin pregnancy. Prenatal ultrasonography at the 20th week of gestation revealed characteristic findings of ARPKD in one fetus. The twins were delivered at 36 weeks gestation. The affected twin died shortly after birth because of severe respiratory distress. Postnatal exome sequencing (ES) on the deceased infant identified a pathogenic homozygous variant in the polycystic kidney and hepatic disease (PKHD1) gene, supporting the genetic diagnosis of ARPKD. DISCUSSION: Management of ARPKD requires multidisciplinary care, emphasizing supportive therapy and monitoring for complications. Genetic counseling is pivotal, highlighting the risk of disease transmission and the role of prenatal genetic screening for at-risk families. CONCLUSIONS: Our case highlights the importance of early diagnosis, comprehensive management, and genetic counseling in ARPKD, particularly within the Jordanian population as well as neighboring demographics with high rates of consanguinity.