RHPD2 is a cystic dysplasia of the kidneys, liver and pancreas. Patients affected by this disorder also suffer from Potter sequence, cardiac anomalies such as truncus arteriosus and unseptated atrium and ventricle, pulmonary defects such as hypoplastic lungs and abnormal lung lobulation, and skeletal deformities such as shortened legs, bowed femurs and talipes equinovarus. RHPD has an onset in-utero and most pregnancies are complicated by oligohydramnios. The prognosis for this disorder is poor with most cases resulting in fetal death. While the prevalence of RHPD is not yet clear, it does not appear to have a gender or ethnic bias.
Diagnosis is made based on clinical features and can be confirmed by genetic analysis. There is currently no cure for the disorder. However, patients’ families may benefit from genetic counselling.
RHPD2 follows an autosomal recessive pattern of inheritance and it is caused by mutations in the NEK8 gene. This gene encodes a ciliary serine/threonine kinase involved in the Hippo signaling pathway. So far, NEK8 variants associated with RHPD2 have been homozygous transitions resulting in nonsense mutations.
Al-Hamed et al. (2016) analysed a cohort of 44 Saudi families with antenatal ultrasound findings of bilateral cystic kidney disease, echogenic kidneys or enlarged kidneys. In one such family, the fetus was found to have cystic kidneys, oligohydramnios, cerebellar vermis aplasia, dilated cisterna magna and bilateral bowed femurs. The case resulted in fetal death and DNA was unavailable for analysis. However, the consanguineous parents were both identified to be heterozygous for a novel NEK8 mutation c.1401G>A (p.W467*).
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