This is a rare inherited disorder that presents problems with multiple-system of the body such as distinctive facial features, problems with the vision, hearing, the kidneys and an abnormal brain development. In addition, they also exhibit intellectual disability and developmental delay. As this is a rare disorder, only a few dozens of cases have been reported.
Causes
This is inherited in an autosomal recessive pattern meaning both the copies of the genes contain the mutation that can cause the disorder. In most of the cases, the parents carry a single copy of the defective gene but don’t necessarily present any symptoms. The mutation in the gene LRP2 is identified to be the cause of donnai-barrow syndrome which is necessary for the production of a protein known as megalin that act as receptors. These are essential in the triggers of signals that are necessary for cell development and function. Megalin is required for several body processes including the function of the brain, central nervous system, reproductive system, eyes, ears and the intestine. The absence of the functional megalin protein causes the features that are characteristic of this disorder.
Symptoms
The distinctive facial features include a prominent forehead, wide-set eyes, short nose with a flattened bridge, missing of certain brain structures such as corpus callosum which connects two parts of the brain and increase of protein in the urine. In addition, they also present developmental delays in several of the cases and seizures. The vision problem includes near-sightedness with increased risk of developing retinal detachment that can result in permanent vision loss and sensorineural hearing loss. They also tend to have a congenital diaphragmatic hernia that can cause serious birth defects where the intestines may move to the chest region affecting the development of the heart and the lungs. In rare cases, abnormalities of other organs may be evident such as the heart and the intestine.
Diagnosis
The diagnosis of this disorder is based on the characteristic clinical features that are identified and with a pattern of low-molecular-weight proteinuria. The diaphragmatic hernia can be identified by the chest x-rays that detects abdominal organs located in the chest cavity. The genetic testing can also diagnose this condition by the detection of the gene megalin, the only gene known to cause this disorder.
Treatment
There is no treatment for this syndrome but surgery can repair the diaphragmatic hernia and corrective lenses can be used for the eye condition (myopia). The retinal detachment can be prevented with various treatments such as peripheral laser photocoagulation. In the cases of hearing impairment, the hearing aids or cochlear implants can benefit these individuals. The intellectually disabled cases may require special educational programs based on the degree of intellectual impairment and anti-epileptic medications can be used in the case of seizures.
References
https://www.ncbi.nlm.nih.gov/books/NBK1878/
http://disorders.eyes.arizona.edu/handouts/donnai-barrow-syndrome
https://ghr.nlm.nih.gov/condition/donnai-barrow-syndrome#diagnosis
