Donnai-Barrow syndrome (DBS) is characterized by typical craniofacial features (ocular hypertelorism, enlarged fontanelle), ocular findings (high myopia, retinal detachment, progressive vision loss, and iris coloboma), sensorineural hearing loss, agenesis of the corpus callosum, intellectual disability, and congenital diaphragmatic hernia (CDH) and/or omphalocele. Both inter- and intrafamilial phenotypic variability are observed.
The diagnosis of DBS is based on the combination of characteristic clinical features and a distinctive pattern of low-molecular-weight proteinuria. LRP2, encoding the protein low-density lipoprotein receptor-related protein 2 precursor (megalin), is the only gene known to be associated with DBS. Molecular genetic testing is available clinically and on a research basis.
DBS is inherited in an autosomal recessive manner. In general, the parents of an affected child are obligate heterozygotes with each carrying one mutant allele; one instance of uniparental disomy has been reported. When both parents are known to be mutation carriers, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier detection for at-risk relatives and prenatal testing of pregnancies at increased risk may be possible through laboratories offering custom mutation testing if both mutations in a family are known.