central precocious puberty, which was supported by her response to treatment with triptorelin.38 Given our data, the deletion of MKRN3 is probably the cause of early puberty in this patient.38 It is uncertain whether the obesity, developmental delay, and high pain threshold in this patient were attributable to the MKRN3 deletion. We have detailed clinical and hormonal data from 12 of the 15 persons with loss-of-function mutations in MKRN3. In this series of 12 patients, 2 had esotropia, which is a minor diagnostic criterion for the Prader–Willi syndrome.28 Other features of the syndrome were not reported. The esotropia cannot be definitively attributed to MKRN3 deletion, because esotropia can be present in up to 5% of the population.39
