Kagami-Ogata syndrome due to maternal 14q32.2 hypermethylation

Kagami-Ogata syndrome (KOS) due to maternal 14q32.2 hypermethylation is a rare imprinting disorder caused by epigenetic alterations at the chromosome 14q32.2 locus. In this specific subtype, abnormal hypermethylation of the maternally inherited differentially methylated region (DMR) leads to silencing of maternally expressed genes (such as MEG3, RTL1as, and MEG8) and overexpression of paternally expressed genes (particularly RTL1 and DLK1) at this imprinted locus. The net effect mimics paternal uniparental disomy of chromosome 14 (upd(14)pat), which is the more common cause of Kagami-Ogata syndrome. This epimutation mechanism accounts for a minority of KOS cases. Kagami-Ogata syndrome primarily affects skeletal, respiratory, and abdominal wall development. Key clinical features present from birth include a distinctive "coat-hanger" appearance of the ribs (bell-shaped thorax with small chest), abdominal wall defects such as omphalocele, polyhydramnios during pregnancy, and placentomegaly. Affected neonates frequently experience severe respiratory difficulties due to the small thorax and may require intensive respiratory support. Characteristic facial features include a full cheeks, depressed nasal bridge, protruding philtrum, and micrognathia. Feeding difficulties are common in infancy. Hepatoblastoma has been reported as a potential complication, warranting surveillance. Developmental delay of variable degree may be present. There is no specific curative treatment for Kagami-Ogata syndrome. Management is supportive and multidisciplinary, focusing on respiratory support in the neonatal period, surgical correction of abdominal wall defects if present, nutritional support for feeding difficulties, and developmental therapies. Tumor surveillance, particularly for hepatoblastoma, may be recommended. With appropriate neonatal intensive care, survival has improved, though the neonatal period remains the most critical phase due to respiratory compromise.

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