Donnai-Barrow syndrome

Donnai-Barrow syndrome (DBS), also known as faciooculoacousticorenal (FOAR) syndrome, is a rare autosomal recessive multisystem disorder caused by mutations in the LRP2 gene, which encodes the protein megalin (also called LRP2). Megalin is a large endocytic receptor expressed in many epithelial tissues and plays a critical role in the reabsorption of proteins and other molecules. Loss of functional megalin leads to widespread developmental and functional abnormalities affecting multiple organ systems. The syndrome is characterized by a distinctive set of clinical features including agenesis or hypoplasia of the corpus callosum, sensorineural hearing loss, high-grade myopia or other ocular abnormalities (such as retinal detachment, iris coloboma, and enlarged globes), diaphragmatic hernia (often congenital), omphalocele, and characteristic facial features including widely spaced eyes (hypertelorism), a short nose, and a flat facial profile. Affected individuals also exhibit low-molecular-weight proteinuria due to impaired renal tubular reabsorption, which is a hallmark biochemical finding. Intellectual disability of variable severity is common, and some patients may have structural cardiac defects. There is currently no cure or disease-specific treatment for Donnai-Barrow syndrome. Management is supportive and multidisciplinary, focusing on surgical correction of diaphragmatic hernia and omphalocele in the neonatal period, hearing aids or cochlear implants for sensorineural hearing loss, ophthalmologic interventions for vision problems, developmental support and early intervention services, and monitoring of renal function. Genetic counseling is recommended for affected families. Prognosis varies depending on the severity of the congenital anomalies, particularly the diaphragmatic hernia, which can be life-threatening in the neonatal period.

Common questions about Donnai-Barrow syndrome