Isolated Hypomethylation of Associated with Severe Hypoglycemia Responsive to Growth Hormone Treatment.

Hypomethylation of and can cause Silver-Russell syndrome (SRS), a clinically and genetically heterogeneous condition characterized by intrauterine growth restriction, poor postnatal growth, relative macrocephaly, craniofacial abnormalities, body asymmetry, hypoglycemia and feeding difficulties. Isolated hypomethylation of has been reported in single cases of SRS as well. Here, we report on a 19-month-old patient who presented with two episodes of hypoglycemic seizures. No intrauterine growth restriction was observed, the patient did not present with SRS-typical facial features, and postnatal growth in the first months of life was along the lower normal percentiles. Exome sequencing did not reveal any likely pathogenic variants explaining the phenotype; however, hypomethylation studies revealed isolated hypomethylation of , while the methylation of appeared normal. Hypoglycemia responded well to growth hormone therapy, and the boy showed good catch-up growth. Our case demonstrates that SRS and isolated hypomethylation should be considered early in the diagnosis of recurrent hypoglycemia in childhood, especially in combination with small gestational age and poor growth.