Faciooculoacousticorenal (FOAR) syndrome [Donnai-Barrow syndrome; DBS/FOAR] is a rare autosomal recessive familial disorder that has resulted from mutations that have occurred on chromosome 2q31.1 of the LRP2 gene. This disorder is minimal in its studies as less than 30 cases have been recorded world wide. DBS/FOAR contains multiple characteristics in identifying the disease. Although research continues around the world, there is no known cure or expectancy of length of life.

Faciooculoacousticorenal (FOAR) Syndrome is the original Online Mendelian Inheritance in Man® (OMIM) name for the rare familial disorder that was first reported more than 30 years ago by Holmes and Schepens [1972]. FOAR syndrome is a rare familial disorder comprising of a prominent brow, flat nasal bridge, ocular hypertelorism, antimongoloid slant of the palpebral fissures, high myopia, iris hypoplasia, or coloboma, catarats, retinal detachment, sensorineural hearing loss, and proteinuria [Regenbogen and Coscas, 1985; Schowalter et al., 1997]. Donnai-Barrow Syndrome (DBS) was originally thought to be a sister or cousin genetically to FOAR syndrome. After further research they found that these two identified disorders were actually the same with a few differences in characteristics.
DBS is listed medically in code as OMIM 222448. It is a rare autosomal recessive disorder characterized by agenesis of the corpus callosum, enlarged anterior fontanelle, hypertelorism, high myopia, severe sensorineural deafness, congenital diaphragmatic hernia, and low molecular weight proteinuria with notable excretion of retinol-binding (RBP) and vitamin D-binding (DBP) proteins [Holmes and Schepens, 1972; Donnai and Barrow, 1993; Kantarci et al., 2007; Kantarci et al., 2008].
Although some of the characteristics are the same, there is no single feature that is characteristic or symptomatic for DBS/FOAR. Even though the main characteristics of both are predominantly noticed at birth, some of the underlying and not so obvious problems, such as a diaphragmatic or umbilical hernia, may need to be found in order to diagnose properly. Even in an instance when a patient is found to have an anterior congenital diaphragmatic hernia, agenesis of the corpus callosum, a large anterior fontanelle, or any other of the disease characteristics that are listed, it is not always a case of DBS/FOAR. Dependency of one variable on another cannot be verified [Metzloff, 2007].

Through both blood and saliva derived genomic DNA samples and genetic sequencing, each patient with the exception of one has been diagnosed with DBS/FOAR by the age of 12. Clinical and diagnostic information based on prenatal imaging and/or postnatal study was collected from 27 various published reports [Pober, Longoni, Noonan; 2008]. In William Ray’s book ‘Methods toward a Science of Behavior and Experience,’ Ray says “in our society, research participants have the same rights during an experiment that they have outside the experimental situation (2003).
Much of the testing and research has been conducted at major universities and hospitals around the world; including, University of Washington School of Medicine, Harvard Medical School in Boston, and Weill Cornell Medical College-Qatar (WCMC-Q). Barbara Pober at Massachusetts Children’s General Hospital in Boston and Ahmed Teebi at WCMC-Q is part of an international team that has reported that mutations in LRP2 cause Donnai-Barrow syndrome (DBS) and facio-oculo-acoustico-renal (FOAR) syndrome. Both doctors are pediatricians and geneticists and are the front runners in the research of DBS/FOAR syndrome.
After extensive research, researchers found that the LRP2 gene was the cause of these malformations of the body. Upon finding the gene that was affected, that noted that the 2q31.1 chromosome was mutated and responsible for the deformities.

A total of 27 patients have tested positive for the mutant LRP2 gene. Of these 27 patients, 14 of them were female and 13 were male. Also it was found that even though not all patients showed signs or symptoms of some of the disorders, the total number of patients that were able to be studied, a yes or no response was usually greater than 50 percent in the patients showing signs of the symptom. Ten cases were deceased at the time of their publication because of pregnancy termination, neonatal death secondary to complications of congenital malformations, or status epilepticus [Pober, Longoni, Noonan; 2008].
The following is a list of the positive and negative symptoms in the patients. Not all numbers indicate the same exact patients.
Of 27 patients, fifteen patients showed positive signs of a congenital diaphragmatic hernia as well as an omphalocele/ umbilical hernia while nine patients did not show any signs of either.
Of 26 patients, all 26 showed positive signs for hypertelorism.
Of 17 patients, seven patients showed positive signs while ten showed negative signs for coloboma and 17 of 17 showed positive signs of high myopia.
Of 18 patients, 18 showed positive signs of some sort of hearing loss while only 17 showed positive signs for agenesis of the corpus callosum.
Of 20 patients, 19 showed positive signs of a large anterior fontanelle while only one showed no sign of a large anterior fontanelle.
Of 15 patients, 13 showed positive signs of developmental delay while two patients did not show any signs of developmental delay.
Of 14 patients, nine patients showed that their occipofrontal circumference was less than the 95th percentile.
Of 12 patients, all 12 showed some positive sign of proteinuria.
There is not enough data or information to measure the mean, median or mode of the patients or their symptoms.
There have been no reports of reproduction in individuals with DBS/FOAR as of August 2008 (Kantarci et al.). It has also been found that the oldest living patient with FOAR syndrome is a 25-year-old male. He has complete vision loss and has had his right globe removed and replaced with a prosthetic globe as well as having prosthetic lenses in both eyes. His intellect is remarkable. He has completed schooling at a school for massage therapy and is working on building his client base currently. He can make his own way around his home and is able to use various electrical appliances with minimal help. His proteinuria is minimal and is virtually undetectable as of his last physical. His hearing is progressively getting worse and requires the use of hearing aids and possible cochlear implants in the future.

Donnai-Barrow syndrome [Faciooculoacousticorenal (FOAR) syndrome]; DBS/FOAR is a rare autosomal recessive disorder resulting from mutations in the LRP2 gene located on chromosome 2q31.1 (NewsRX, 2008). This genetic disorder is coded by the OMIM as 222448. Four other names such as Holmes-Schepens syndrome, diaphragmatic hernia-exomphalos-hypertelorism syndrome, diaphragmatic hernia-hypertelorism-myopia-deafness syndrome, and syndrome of ocular and facial anomilies, telecanthus and deafness should no longer be used when referring to DBS/FOAR (Kantarci et al., 2008).
The difference between DBS and FOAR is that DBS patients have a high risk of an agenesis (failure) of the corpus callosum, intestinal malrotation, exomphalos (a weakness of an infant’s abdominal wall), seizures, congenital diaphragmatic hernia (born with a hernia of the diaphragm) and/ or omphalocele (an umbilical hernia). Other characteristics that both names share in common include hypertelorism (abnormally increased distance between two organs or bodily parts), severe sensorineural deafness, severe myopia (nearsightedness), facial dysmorphia, downslanting palpebral fissures (the horizontal slit of the eye is slanted downward), iris coloboma (a hole, usually keyshaped in the eye), retinal detachment, a short bulbous nose, and posteriorly rotated ears.
Although the differences between DBS and FOAR are minimal, they are connected by the same mutation of the LRP2 gene. This mutation is genetically passed down both paternal and maternal; only one instance has the disease been passed down only paternally. The probability of a child having DBS/FOAR if their parents have all the markers is 25% probability, a 50% probability that they will be a carrier and 25% probability that they will neither be a carrier nor inherit the syndrome.
This information is limited due to the minimal case studies that have been reported. Although other cases have been suggested, they have not been studied and therefore have limited the research to only a small amount of patients who have been diagnosed with DBS/FOAR. In 2008, Pober noted that all the patients that had been studied had been from only 15 different families (2008).
Gripp et al. reported in 1997 that a male infant had been born to a healthy 29-year-old mother and a healthy 30-year-old father who had also had two healthy older daughters. This infant was reported to have omphalocele, causing death two hours after birth (Gripp et al., 1997).
An 11-year-old boy was diagnosed with faciooculoacousticorenal syndrome after doctors had determined that he had sensorineural hearing loss, reduced vision in his right eye, high myopia, cataracts, coloboma, facial dysmorphia, and proteinuria. His psychomotor development however was normal compared to previous studies (Schowalter et al., 1997).
In conclusion no one case of DBS/FOAR is alike. Each case is different not only in the aspect of which characteristics are found in the patients but also in the varying severity of each characteristic. Although there have not been any findings for a cure or in terms of an average life span, the studies are continuous around the world. Further data may be available through research in the near future.

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