Expansion of the phenotype in ZFX neurodevelopmental disorder in a family

With new and increasingly sensitive techniques for genetic testing, genes that are newly related to a phenotype or disease are still identified, warranting for adequate phenotyping. Recently, 11 variants in the ZFX gene were reported to cause a distinct X-linked neurodevelopmental disorder in 18 male patients, and a female was reported with hyperparathyroidism in concurrence with a ZFX variant. In this report, we present a male patient and his mother with a new likely pathogenic variant in the ZFX gene (NM_003410.4(ZFX): c.2363C > G, p. Pro788Arg). The phenotype of the patient includes a global neurodevelopmental delay and several additional features greatly overlapping with the phenotype in previously described patients, including facial features, hypotonia, diminished white matter and thin corpus callosum, inguinal and umbilical herniation, and ophthalmological abnormalities. An elevated PTH was noted, with normocalcemia, a possible early sign of hyperparathyroidism. Additionally, a small colon, signs of a bleeding diathesis and a cervical swelling of non-specific origin were present, which were not reported in patients with ZFX variants before. The mother presents with fatigue, low iron status and a slight elevation of PTH with normocalcemia. This report adds valuable data to the phenotypical spectrum of the ZFX-related neurodevelopmental disorder.