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

Kagami-Ogata syndrome (KOS) due to maternal 14q32.2 microdeletion is a rare imprinting disorder caused by a small deletion on the maternally inherited chromosome 14 within the 14q32.2 region. This region contains a cluster of imprinted genes, including MEG3, RTL1, and DLK1, whose expression is regulated by a differentially methylated region (DMR). When the maternal copy of this regulatory region is deleted, it leads to loss of expression of maternally expressed genes and overexpression of paternally expressed genes, particularly RTL1, which is a key driver of the clinical phenotype. This specific molecular mechanism is one of several that can cause Kagami-Ogata syndrome, alongside paternal uniparental disomy of chromosome 14 and epimutations. The syndrome primarily affects skeletal, respiratory, and abdominal organ systems. Key clinical features present from birth include a distinctive "coat-hanger" appearance of the ribs (bell-shaped thorax with characteristic rib abnormalities), polyhydramnios during pregnancy, placentomegaly, abdominal wall defects (particularly omphalocele), and a characteristic facial appearance with full cheeks, depressed nasal bridge, protruding philtrum, and micrognathia. Affected infants frequently experience significant respiratory difficulties due to the small thorax and may require prolonged ventilatory support. Feeding difficulties, developmental delay, and intellectual disability of variable degree are common. Hepatoblastoma has been reported as a potential complication, warranting surveillance. There is currently no cure or disease-specific treatment for Kagami-Ogata syndrome. Management is supportive and multidisciplinary, focusing on respiratory support in the neonatal period, surgical correction of abdominal wall defects when present, nutritional support for feeding difficulties, and developmental interventions. With appropriate neonatal intensive care, survival has improved, though the thoracic abnormalities tend to improve with age. Long-term follow-up includes monitoring for hepatoblastoma and addressing developmental and educational needs.

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