Grünert Sarah C, Matysiak Uta, Hodde Franka, Ruzaike Gunda, Lausch Ekkehart, Schumann Anke, van der Werf-Grohmann Natascha, Spiekerkoetter Ute, Schmidts Miriam
Department of General Paediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre-University of Freiburg, 79106 Freiburg, Germany.
Diagnostics (Basel). 2021 Apr 22;11(5):749. doi: 10.3390/diagnostics11050749.
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.
H19和IGF2的低甲基化可导致Silver-Russell综合征（SRS），这是一种临床和遗传异质性疾病，其特征为宫内生长受限、出生后生长发育不良、相对巨头畸形、颅面异常、身体不对称、低血糖和喂养困难。在SRS的个别病例中也报道过孤立的H19低甲基化情况。在此，我们报告一名19个月大的患者，该患者出现了两次低血糖惊厥。未观察到宫内生长受限，患者没有表现出SRS典型的面部特征，且出生后最初几个月的生长发育处于较低的正常百分位。外显子组测序未发现任何可能解释该表型的致病变异；然而，低甲基化研究显示存在孤立的H19低甲基化，而IGF2的甲基化似乎正常。低血糖对生长激素治疗反应良好，该男孩表现出良好的追赶生长。我们的病例表明，在儿童复发性低血糖的诊断中，尤其是结合孕周小和生长发育不良时，应早期考虑SRS和孤立的H19低甲基化。
