The broad GNAS epigenetic defects seen in the sporadic cases are often such that the maternal allele has attained a paternal epigenotype. Accordingly, a sporadic PHP-Ib case has been shown to have paternal uniparental isodisomy of the entire chromosome 20q (patUPD20q) [90]. Leading to the diagnosis were PTH-resistance and mild TSH resistance in the absence of typical AHO findings, although the patient had additional abnormalities, including developmental delay and craniosynostosis, which may have resulted from either disrupted expression of other imprinted genes or from unmasking of recessive defects present on paternal chromosome 20q. Hence, patUPD20q is a cause of sporadic PHP-Ib, and it is possible that interstitial paternal UPDs in this region could lead to PHP-Ib as a more common cause of this disorder in the sporadic cases. It has also been suggested that some cases of sporadic PHP-Ib is caused by stochastic defects in the imprinting process [162]. In either case, the offspring of affected females would be predicted to have normal GNAS imprinting and normal proximal tubular PTH responsiveness even if they inherit the disease-associate allele.
