Galloway-Mowat syndrome

Galloway-Mowat syndrome (GAMOS) is a rare, severe autosomal recessive disorder characterized by the combination of early-onset nephrotic syndrome and central nervous system abnormalities, particularly microcephaly. The condition was first described by Galloway and Mowat in 1968. It affects multiple body systems, most prominently the kidneys and the brain. Renal involvement typically manifests as nephrotic syndrome with proteinuria, often progressing to end-stage renal disease. The kidney pathology most commonly shows diffuse mesangial sclerosis or focal segmental glomerulosclerosis. Neurological features include microcephaly, intellectual disability, seizures, and structural brain anomalies such as gyral abnormalities (including lissencephaly, pachygyria, or polymicrogyria), cerebellar hypoplasia, and corpus callosum abnormalities. Additional features may include facial dysmorphism (such as a large or low-set ears, hypertelorism, and micrognathia), hiatal hernia, and growth retardation. Genetic studies have identified multiple causative genes, most of which encode components of the KEOPS complex involved in a universal tRNA modification (t6A modification). These genes include WDR73, OSGEP, TP53RK, TPRKB, LAGE3, GON7, NUP107, NUP133, and WDR4, among others. The genetic heterogeneity of the condition means that clinical severity can vary, though the prognosis is generally poor, with many affected children dying in infancy or early childhood due to renal failure or neurological complications. There is currently no cure or disease-specific treatment for Galloway-Mowat syndrome. Management is supportive and symptomatic, focusing on controlling nephrotic syndrome (with ACE inhibitors, albumin infusions, and potentially dialysis or renal transplantation for end-stage renal disease), managing seizures with anticonvulsant medications, and providing developmental support. Nutritional support and physical therapy may also be beneficial. Genetic counseling is recommended for affected families.

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