Galloway-Mowat syndrome

Galloway-Mowat syndrome is a very rare genetic disorder, usually inherited in an autosomal recessive pattern, that combines several distinct features: a hiatal hernia (a defect that allows part of the stomach to push through the diaphragm), microcephaly (an abnormally small head, reflecting impaired brain development), and nephrotic syndrome (a kidney disorder that lets protein leak into the urine). The combination of a structural defect, a neurological finding, and a kidney disorder in the same inherited condition is what distinguishes the syndrome from any single-organ disease with a similar name. Its underlying cause was long a mystery, but research has since tied it to disruption of the KEOPS/EKC protein complex, a cellular machine responsible for a chemical modification of transfer RNA that is needed for accurate protein production; mutations in several genes that make up or support this complex, including OSGEP, TP53RK, TPRKB and LAGE3, have been identified in affected families. As of 2020 roughly ten genes were known to cause the syndrome, with LAGE3 notably associated with an X-linked rather than autosomal recessive inheritance pattern in some cases, showing that what was first described as a single syndrome reflects several related genetic causes converging on the same combination of features.